Michael Harrop
Active member
Not even close. Read my report I linked earlier. I have yet to find a good enough stool donor that can restore eubiosis.
Suppose that the gut/brain axis is as important (in psychiatry) as the peer-reviewed literature seems to indicate. Why then isn't fecal transplantation an extremely famous and celebrated psychiatric treatment?
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OP
GutBrainAxis
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1: I find it super depressing to think that we've done irreparable and permanent damage to our gut biota. I know I mentioned this before, but aren't hunter-gatherers who've never made contact with modern medicine able to provide samples that can allow us to (at least in principle) undo the damage that we've done? It's obviously scary and disturbing to think that we've smashed an important part of humanity (the gut biota)...something that we don't remotely understand and whose value and function we're only starting to learn about. I hope that the damage that's been done isn't irreparable and permanent.
2: I would assume that tapping into the gut biota of other apes isn't useful to us in terms of reconstructing the pre-civilization human microbiome, right?
3: Would the pre-civilization human microbiome be better than anything newer? I'm sure that we started to change our gut biota long before modern medicine came along; not sure whether those changes have been significantly harmful every step of the way.
2: I would assume that tapping into the gut biota of other apes isn't useful to us in terms of reconstructing the pre-civilization human microbiome, right?
3: Would the pre-civilization human microbiome be better than anything newer? I'm sure that we started to change our gut biota long before modern medicine came along; not sure whether those changes have been significantly harmful every step of the way.
OP
GutBrainAxis
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1: I'm going through a weird situation. I woke up today feeling better than I've basically ever felt in my whole adult life. It seems like I got a "B-Complex" pill (it has all the B vitamins and some other stuff) to absorb properly in my duodenum or whatever. I also did take a vitamin D and an Omega-3 supplement last, but I suspect that it was the "B-Complex" thing that worked the magic. I've taken those same substances (that are in the "B-Complex" pill) before, but I don't think that anything really absorbed properly before. The big wild card is obviously the gut biota. Did the gut biota mediate this "miracle effect" that I woke up with today? Obviously gut biota do metabolize the stuff that the "B-Complex" pill had in it. It's just so hard to try to unravel what role my gut biota might be playing.
2: I think that it's crucial to focus on absorption. It seems like the duodenum is the place where all the important nutrients (pretty much?) are supposed to absorb. If I had some bacterial overgrowth or inflammation or Celiac Disease or...if I had something that was blocking absorption, then that would explain this experience. I removed whatever barricade (in my duodenum) was blocking absorption. And now my brain is experience the "B-Complex" stuff for the first time. Does that all make sense?
3: Strangely, after a few hours of enjoying the "miracle effect", I ate a snack-bar thing (it's gluten-free and its only ingredients are dates, peanuts, and peanut butter...I eat peanut butter all the time so I don't think that I have any peanut allergy) and the snack-bar thing absolutely destroyed me. My brain was foggy. I had waves of anxiety. I had bad images in my mind. I was moaning. I felt cold. I could barely move due to fatigue; I was practically immobilized. So that really interrupted the "miracle effect". And I ate some blueberry yogurt later and (due to the yogurt) experienced another "attack". What do you make of these weird "attacks"?
2: I think that it's crucial to focus on absorption. It seems like the duodenum is the place where all the important nutrients (pretty much?) are supposed to absorb. If I had some bacterial overgrowth or inflammation or Celiac Disease or...if I had something that was blocking absorption, then that would explain this experience. I removed whatever barricade (in my duodenum) was blocking absorption. And now my brain is experience the "B-Complex" stuff for the first time. Does that all make sense?
3: Strangely, after a few hours of enjoying the "miracle effect", I ate a snack-bar thing (it's gluten-free and its only ingredients are dates, peanuts, and peanut butter...I eat peanut butter all the time so I don't think that I have any peanut allergy) and the snack-bar thing absolutely destroyed me. My brain was foggy. I had waves of anxiety. I had bad images in my mind. I was moaning. I felt cold. I could barely move due to fatigue; I was practically immobilized. So that really interrupted the "miracle effect". And I ate some blueberry yogurt later and (due to the yogurt) experienced another "attack". What do you make of these weird "attacks"?
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OP
GutBrainAxis
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1: Regarding the "attacks" that I mentioned, is it possible that I have extreme dysbiosis and that the extreme dysbiosis means that any new food causes a big negative reaction? Sometimes foods that I've eaten many times will cause my gut to go ballistic; maybe it's just the fact that my regular diet has been interrupted...maybe it's not about what I eat so much as whether that food happens to be new to my gut biota. Anything new is an interruption that causes a big nuclear response, maybe; is there any science supporting that notion?
2: I have no doubt that my gut biota have been in flux lately. And have been in flux for years now as my diet (often extremely unhealthy) has shifted around. Can gut-biota changes cause someone to suddenly have food intolerances that they never had previously?
3: Could I get tested for various food intolerances?
4: But if I get tested for various food intolerances, what if my gut-biota situation shifts and then the tests that I've done therefore become obsolete?
5: Should I get my gut biota tested? I know that little is known about gut biota, but it seems useful nonetheless.
6: Is it possible (and is it likely?) that someone like me (who's had a bad diet and who definitely has something weird going on with their gut) will find (thanks to gut-biota testing) pathogenic bacteria that don't need to be "balanced" in any way and should simply be eliminated? I'm not sure how likely it is that my (evidently very unhealthy) gut has actual pathogenic bacteria in it, but who knows; regarding pathogenic bacteria, an infection would explain a lot, so I wonder how likely it is that testing would reveal something on that front in my own case.
7: Is the problem that there are just a lot of contradictory results about what kind of gut biota are the ideal ones to have? Is that way it's hard for one to look at one's gut-biota composition and say "OK, I need to adjust this and this and this"?
8: Without any "compass" that allows one to move toward an ideal gut-biota composition, is it best to just tinker around and see which adjustments lead to better brain function and better mood and better energy? Can a trial-and-error approach lead someone in the right direction even without any "compass" from the biologists?
9: Is it known why "dynamic equilibrium" emerges from dysbiosis? I think of it like swarming bees; a healthy swarm will scatter (when you throw a rock) but then return to some "equilibrium", whereas an unhealthy swarm just scatters and only very partially returns to the original swarming pattern. I'm not sure exactly what factors restore "dynamic equilibrium" after dysbiosis has befallen someone's gut.
10: What does science have to say about how bad dysbiosis can actually get? For example, can it get to the point where every single food you eat (that's not part of your regular diet) causes chaos in terms of your gut biota?
2: I have no doubt that my gut biota have been in flux lately. And have been in flux for years now as my diet (often extremely unhealthy) has shifted around. Can gut-biota changes cause someone to suddenly have food intolerances that they never had previously?
3: Could I get tested for various food intolerances?
4: But if I get tested for various food intolerances, what if my gut-biota situation shifts and then the tests that I've done therefore become obsolete?
5: Should I get my gut biota tested? I know that little is known about gut biota, but it seems useful nonetheless.
6: Is it possible (and is it likely?) that someone like me (who's had a bad diet and who definitely has something weird going on with their gut) will find (thanks to gut-biota testing) pathogenic bacteria that don't need to be "balanced" in any way and should simply be eliminated? I'm not sure how likely it is that my (evidently very unhealthy) gut has actual pathogenic bacteria in it, but who knows; regarding pathogenic bacteria, an infection would explain a lot, so I wonder how likely it is that testing would reveal something on that front in my own case.
7: Is the problem that there are just a lot of contradictory results about what kind of gut biota are the ideal ones to have? Is that way it's hard for one to look at one's gut-biota composition and say "OK, I need to adjust this and this and this"?
8: Without any "compass" that allows one to move toward an ideal gut-biota composition, is it best to just tinker around and see which adjustments lead to better brain function and better mood and better energy? Can a trial-and-error approach lead someone in the right direction even without any "compass" from the biologists?
9: Is it known why "dynamic equilibrium" emerges from dysbiosis? I think of it like swarming bees; a healthy swarm will scatter (when you throw a rock) but then return to some "equilibrium", whereas an unhealthy swarm just scatters and only very partially returns to the original swarming pattern. I'm not sure exactly what factors restore "dynamic equilibrium" after dysbiosis has befallen someone's gut.
10: What does science have to say about how bad dysbiosis can actually get? For example, can it get to the point where every single food you eat (that's not part of your regular diet) causes chaos in terms of your gut biota?
Michael Harrop
Active member
Indeed.
Discussed here https://www.humanmicrobes.org/blog/half-a-million-stool-donor-applicants
You lack the microbes needed to digest those foods properly.
Definitely.
An elimination diet is the best option. https://humanmicrobiome.info/diet/#elimination-diets
I'd say no. https://humanmicrobiome.info/testing/
It's currently the only option.
I've been there.
OP
GutBrainAxis
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Sorry for leaving three comments; that was a lot of stuff to respond to. Did you see all the questions? Just checking that you saw them all and responded to what you wanted to address.
I'm curious about this:
Is it known why "dynamic equilibrium" emerges from dysbiosis? I think of it like swarming bees; a healthy swarm will scatter (when you throw a rock) but then return to some "equilibrium", whereas an unhealthy swarm just scatters and only very partially returns to the original swarming pattern. I'm not sure exactly what factors restore "dynamic equilibrium" after dysbiosis has befallen someone's gut.
You might mention this in your link on gut-biota testing, but there are different gut biota throughout the GI system...how can one test when there's so much variation throughout?
I myself am really focused on trying to find out what the deal is with my duodenum. That's the spot where a lot of nutrients get absorbed. I experienced an incredible effect that seemed to come from taking a "B-Complex" supplement. But the effect only lasted one day. I wonder if the "tachyphylaxis" that I experience (regarding both medications and nutrients) occurs because my gut biota "adapt"...in other words, my gut biota aren't "ready" for the medication/supplement when I first take the substance but then the second time I take the substance the gut biota are "ready" (they've "adapted") and they "intercept" the substance and prevent my body from being able to absorb the substance. Is that at all possible?
Is there literature that I could read on that whole phenomenon of gut-biota "interception" of medications and supplements? This "interception" must be occurring in the duodenum.
This will sound odd, maybe, but I sometimes get the feeling that when I take a substance it will either go into the blood (the duodenum is where this happens, I think) or else it will continue forward into the gut. I took some lithium and my whole gut roared to life and made so many sounds. My whole gut was like a symphony of noise; lithium has a major impact on the gut biota (can't recall if lithium also has a direct effect on the gut itself). Anyway, my question was why lithium was having this impact throughout my whole gut; why didn't the lithium enter my blood at the duodenum? It's like the duodenum is an "off-ramp" and one has to ask why a substance stays in the gut rather than leaving at the duodenum. What factors determine whether the "off-ramp" is taken or not? Or to what extent it's taken?
See here:
https://www.sciencedirect.com/science/article/abs/pii/S1043661821005764
What exact condition is it thought that you have, by the way? I'm surprised that with your incredible knowledge and dedication you've been unable to solve the puzzle. For example, I'm sure that you've tried a careful elimination-diet strategy.
1: Will phage treatment maybe turn out to be the key treatment that's used to improve people's gut-biota situation? I saw this thing that you linked to in one of your wikis: https://www.frontiersin.org/articles/10.3389/fcimb.2019.00348/full.
2: How do people's phages get either depleted or (compositionally) messed up in the first place?
3: Is there no DIY way to find out each of the below things?
- how fast your stomach empties (seems like rapid gastric emptying would be pretty easily detectable...just ingest something that induces a reaction in your gut and then count how many seconds till that reaction occurs)
- whether a given drug or nutrient pill is being absorbed into the blood or not (it seems to me like the duodenum is like an "off-ramp" and that if stuff isn't absorbed at the duodenum then it'll basically travel through your whole gut...so if something is impacting your entire small intestine then you'd think that the "off-ramp" was missed and that absorption didn't occur and that the substance didn't absorb and therefore continued forward through the gut)
This seems important, by the way:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224655/
Bile salt hydrolase (BSH; EC 3.5.1.24) is an enzyme produced by the intestinal microbiota that catalyzes the hydrolysis of amide bonds in conjugated BAs, resulting in the release of free amino acids [20]. These enzymes belong to the N-terminal nucleophilic (Ntn) hydrolase superfamily and share a similar αββα-core structure to an N-terminal catalytic cysteine residue [20]. This residue is critical to the catalysis mechanism and acts both as a nucleophile and a proton donor [21]. The N-terminal amino group serves as the proton acceptor and activates the nucleophilic thiol group of the cysteine side chain. Besides the cysteine residue, other amino acids conserved in most BSHs are also relevant to the catalytic reaction, including Arg18, Asp21, Asn82, Asn175, and Arg228 [20]. Numerous studies aimed to define the key amino acids and the secondary structural elements that are potentially involved in the substrate binding in BSHs [22,23]. These reports showed that BSHs are able to recognize their substrates via hydrophobic interactions with steroid moiety [24,25]. From the BSHs discovered, mainly intracellular enzymes were characterized as being from the Bacteroides fragilis, Bacteroides vulgatus, Clostridium perfringens, Listeria monocytogenes, Lactobacillus, and Bifidobacterium species [14]. Although most enzymes exhibited a similar overall topology, they displayed different catalytic efficiencies and substrate specificities. Additional biochemical reports suggested that around 58% of purified BSHs could recognize glyco-conjugated BAs [26]. To date, little data are available on the structural basis of BSH functions. Only five three-dimensional structures of the BSH enzymes from Bifidobacterium longum [27], Lactobacillus salivarius [23], Enterococcus faecalis [28], Clostridium perfringens [25], and Bacteroides thetaiotaomicron VPI-5482 [29] were reported.
...
BSH enzymes play important roles in a wide range of host metabolic processes, including the regulation of cholesterol metabolism, energy, and inflammation homeostasis. BSHs have mainly been described in lactic acid bacteria. However, functional analysis of the gut microbiota revealed a high number of these enzymes in this ecological niche. The modulation of such activity has been shown to exhibit widespread effects on the host and resident microbiota. As the unique enzymes involved in the crucial deconjugation reaction, BSHs may serve as a promising strategy to control numerous diseases ranging from metabolic disorders to inflammatory and infectious diseases. Studies highlighting the molecular aspects of BSH enzymes including protein structure and genetic regulation would certainly be of great relevance to fully address and evaluate the implications of BSHs as a clinical tool.
1: I drank some tea tonight that had various things in it (ginger root, lemongrass, peppermint leaves, fennel seeds, chicory root, lemon balm, and lemon peel). Weirdly, it seems like these things (starting with ginger) are supposed to soothe the gut and not inflame it. But this tea absolutely messed me up; I was completely spaced out and my whole brain was basically shut off. It was rough. I was extremely tired too, with no longer. Interestingly, I took some curcumin and that basically got rid of all the bad effects that the tea had caused. Curcumin is supposed to combat inflammation, right? I guess that the tea caused inflammation in my gut...I have no idea why.
2: It might be useful for me to isolate which of the tea's ingredients caused the negative impact, right? I wonder if figuring that out might provide a clue as to what's wrong with me.
3: Have you seen the paper below? Make sure to read the whole piece of text that I pasted below because it talks about dysbiosis.
https://pubmed.ncbi.nlm.nih.gov/31610413/
To what extent are the products below actually effective? And actually based on solid science?
- https://www.gutfood.com/
- https://www.healthyplanetcanada.com/natural-factors-pgxr-daily-ultra-matrix-softgels-750mg-240-softgels.html
I'm curious about this:
Is it known why "dynamic equilibrium" emerges from dysbiosis? I think of it like swarming bees; a healthy swarm will scatter (when you throw a rock) but then return to some "equilibrium", whereas an unhealthy swarm just scatters and only very partially returns to the original swarming pattern. I'm not sure exactly what factors restore "dynamic equilibrium" after dysbiosis has befallen someone's gut.
You might mention this in your link on gut-biota testing, but there are different gut biota throughout the GI system...how can one test when there's so much variation throughout?
I myself am really focused on trying to find out what the deal is with my duodenum. That's the spot where a lot of nutrients get absorbed. I experienced an incredible effect that seemed to come from taking a "B-Complex" supplement. But the effect only lasted one day. I wonder if the "tachyphylaxis" that I experience (regarding both medications and nutrients) occurs because my gut biota "adapt"...in other words, my gut biota aren't "ready" for the medication/supplement when I first take the substance but then the second time I take the substance the gut biota are "ready" (they've "adapted") and they "intercept" the substance and prevent my body from being able to absorb the substance. Is that at all possible?
Is there literature that I could read on that whole phenomenon of gut-biota "interception" of medications and supplements? This "interception" must be occurring in the duodenum.
This will sound odd, maybe, but I sometimes get the feeling that when I take a substance it will either go into the blood (the duodenum is where this happens, I think) or else it will continue forward into the gut. I took some lithium and my whole gut roared to life and made so many sounds. My whole gut was like a symphony of noise; lithium has a major impact on the gut biota (can't recall if lithium also has a direct effect on the gut itself). Anyway, my question was why lithium was having this impact throughout my whole gut; why didn't the lithium enter my blood at the duodenum? It's like the duodenum is an "off-ramp" and one has to ask why a substance stays in the gut rather than leaving at the duodenum. What factors determine whether the "off-ramp" is taken or not? Or to what extent it's taken?
See here:
https://www.sciencedirect.com/science/article/abs/pii/S1043661821005764
What exact condition is it thought that you have, by the way? I'm surprised that with your incredible knowledge and dedication you've been unable to solve the puzzle. For example, I'm sure that you've tried a careful elimination-diet strategy.
1: Will phage treatment maybe turn out to be the key treatment that's used to improve people's gut-biota situation? I saw this thing that you linked to in one of your wikis: https://www.frontiersin.org/articles/10.3389/fcimb.2019.00348/full.
2: How do people's phages get either depleted or (compositionally) messed up in the first place?
3: Is there no DIY way to find out each of the below things?
- how fast your stomach empties (seems like rapid gastric emptying would be pretty easily detectable...just ingest something that induces a reaction in your gut and then count how many seconds till that reaction occurs)
- whether a given drug or nutrient pill is being absorbed into the blood or not (it seems to me like the duodenum is like an "off-ramp" and that if stuff isn't absorbed at the duodenum then it'll basically travel through your whole gut...so if something is impacting your entire small intestine then you'd think that the "off-ramp" was missed and that absorption didn't occur and that the substance didn't absorb and therefore continued forward through the gut)
This seems important, by the way:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224655/
Bile salt hydrolase (BSH; EC 3.5.1.24) is an enzyme produced by the intestinal microbiota that catalyzes the hydrolysis of amide bonds in conjugated BAs, resulting in the release of free amino acids [20]. These enzymes belong to the N-terminal nucleophilic (Ntn) hydrolase superfamily and share a similar αββα-core structure to an N-terminal catalytic cysteine residue [20]. This residue is critical to the catalysis mechanism and acts both as a nucleophile and a proton donor [21]. The N-terminal amino group serves as the proton acceptor and activates the nucleophilic thiol group of the cysteine side chain. Besides the cysteine residue, other amino acids conserved in most BSHs are also relevant to the catalytic reaction, including Arg18, Asp21, Asn82, Asn175, and Arg228 [20]. Numerous studies aimed to define the key amino acids and the secondary structural elements that are potentially involved in the substrate binding in BSHs [22,23]. These reports showed that BSHs are able to recognize their substrates via hydrophobic interactions with steroid moiety [24,25]. From the BSHs discovered, mainly intracellular enzymes were characterized as being from the Bacteroides fragilis, Bacteroides vulgatus, Clostridium perfringens, Listeria monocytogenes, Lactobacillus, and Bifidobacterium species [14]. Although most enzymes exhibited a similar overall topology, they displayed different catalytic efficiencies and substrate specificities. Additional biochemical reports suggested that around 58% of purified BSHs could recognize glyco-conjugated BAs [26]. To date, little data are available on the structural basis of BSH functions. Only five three-dimensional structures of the BSH enzymes from Bifidobacterium longum [27], Lactobacillus salivarius [23], Enterococcus faecalis [28], Clostridium perfringens [25], and Bacteroides thetaiotaomicron VPI-5482 [29] were reported.
...
BSH enzymes play important roles in a wide range of host metabolic processes, including the regulation of cholesterol metabolism, energy, and inflammation homeostasis. BSHs have mainly been described in lactic acid bacteria. However, functional analysis of the gut microbiota revealed a high number of these enzymes in this ecological niche. The modulation of such activity has been shown to exhibit widespread effects on the host and resident microbiota. As the unique enzymes involved in the crucial deconjugation reaction, BSHs may serve as a promising strategy to control numerous diseases ranging from metabolic disorders to inflammatory and infectious diseases. Studies highlighting the molecular aspects of BSH enzymes including protein structure and genetic regulation would certainly be of great relevance to fully address and evaluate the implications of BSHs as a clinical tool.
1: I drank some tea tonight that had various things in it (ginger root, lemongrass, peppermint leaves, fennel seeds, chicory root, lemon balm, and lemon peel). Weirdly, it seems like these things (starting with ginger) are supposed to soothe the gut and not inflame it. But this tea absolutely messed me up; I was completely spaced out and my whole brain was basically shut off. It was rough. I was extremely tired too, with no longer. Interestingly, I took some curcumin and that basically got rid of all the bad effects that the tea had caused. Curcumin is supposed to combat inflammation, right? I guess that the tea caused inflammation in my gut...I have no idea why.
2: It might be useful for me to isolate which of the tea's ingredients caused the negative impact, right? I wonder if figuring that out might provide a clue as to what's wrong with me.
3: Have you seen the paper below? Make sure to read the whole piece of text that I pasted below because it talks about dysbiosis.
https://pubmed.ncbi.nlm.nih.gov/31610413/
To what extent are the products below actually effective? And actually based on solid science?
- https://www.gutfood.com/
- https://www.healthyplanetcanada.com/natural-factors-pgxr-daily-ultra-matrix-softgels-750mg-240-softgels.html
Michael Harrop
Active member
That's probably a decent analogy. However, a healthy swam will scatter less as well.
More so different percentages, as different ones thrive in different environments.
Yes.
There's some here https://humanmicrobiome.info/intro/#drugs
Virtually everything you ingest will have an impact on the gut microbiome.
I already answered that. All the knowledge in the world is completely useless if you can't obtain a high-quality FMT donor.
Antibiotics can do it https://humanmicrobiome.info/antibiotics/#virome.
Yes. https://humanmicrobiome.info/bile/
It "scattered the swarm".
Maybe.
You'll have to check the websites to see if they give citations, then check the citations. And results will vary from person to person.
OP
GutBrainAxis
Member
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- Thread Starter
- #58
1: What is your time frame in terms of when you think you might make major progress regarding your effort to secure really good samples of human feces?
2: I was just reading about the incredible things that this molecule ( https://en.wikipedia.org/wiki/Tryptamine ) does. Could one actually take a supplement of that molecule? And would that be helpful? Are there studies on the supplementation of tryptamine or the supplementation of other things that are similar to tryptamine ( https://en.wikipedia.org/wiki/Trace_amine-associated_receptor )? See here: from the first article I linked:
3: What do you think about the issue where elimination diets (and other "narrow" diets if there are indeed other useful "narrow" ones) might cause a major problem? If you have a "narrow" diet, you'll narrow the composition of your gut biota, won't you? Won't narrowing your gut-biota composition create a major problem where you won't be able to add back various foods since a lot of types of gut biota will have died off because you've starved them?
4: What are some good things to read on the need to have a diet that varies a lot? I have no concept of how much variation is necessary in order to ensure a good situation in terms of gut biota. I'm not really sure what variation even means; there are a million ways one could vary their diet and I don't know which forms of variation (e.g., is timing of nutrients important...like should you eat X for breakfast one day and for dinner the next day?) matter for health regarding gut biota.
5: Where can I find out how the duodenum works? I'm really confused. My impression (strange though it is) is that there's an "off-ramp" at the start of my gut (the "off-ramp" is the duodenum). And that sometimes the contents of a nutrient-supplement pill (or of a medication pill) will go 100% into my blood at the off-ramp and go no further. And that sometimes 0% of the contents of a nutrient-supplement pill (or of a medication pill) will go into my blood and the contents will instead continue forward into my gut and cause a bunch of activity in my gut.
6: I wonder how long a substance spends in the duodenum; is it possible to have a condition where substances spend too little time in the duodenum and just move through and miss the "off-ramp"? What's that condition called and how can it be treated? And if the substances spend adequate time in the duodenum, then what factors determine what % of something enters the blood and what % continues forward into the gut?
7: I do know that a strikingly low % of (e.g.) magnesium will absorb if you ingest a magnesium pill. That's what I thought I read, anyway. Not sure what factors cause that % to be so low.
8: It's obviously an extremely huge deal whether stuff enters your blood or instead feeds your gut biota, right? I mean, one needs to have some control over whether a substance continues forward into the gut (and thus feeds the gut biota), correct?
9: Does your body have any way to say "The gut and/or the gut biota really need this substances, so I'll close off the door to the blood and shunt this stuff into the gut"?
10: If the off-ramp is really good at absorbing stuff then won't 0% of a given substance get past? And won't the gut biota be starved when it comes to that substance?
11: It's probably a good thing if the gut biota are starved of particular substances, but you don't want to starve them of like every major nutrient, right?
12: So too much off-ramp efficiency would like wipe out your gut biota, right?
13: Why aren't all nutrient supplements (and all medications) that are intended to enter the blood just take under the tongue? Why send stuff into the gut if there are so many factors (gut-wise) that might prevent the substance from entering the blood? I do have a B12 supplement that's sublingual but I've never heard of lots of things (e.g., ADHD medications) being sublingual.
14: If someone were able to do so safely (like if they were a millionaire), would it be ideal to get nutrients and medications just injected into your veins?
15: Wouldn't getting things injected into your veins allow you to easily see the extent to which your gut and your gut biota were preventing proper absorption?
2: I was just reading about the incredible things that this molecule ( https://en.wikipedia.org/wiki/Tryptamine ) does. Could one actually take a supplement of that molecule? And would that be helpful? Are there studies on the supplementation of tryptamine or the supplementation of other things that are similar to tryptamine ( https://en.wikipedia.org/wiki/Trace_amine-associated_receptor )? See here: from the first article I linked:
3: What do you think about the issue where elimination diets (and other "narrow" diets if there are indeed other useful "narrow" ones) might cause a major problem? If you have a "narrow" diet, you'll narrow the composition of your gut biota, won't you? Won't narrowing your gut-biota composition create a major problem where you won't be able to add back various foods since a lot of types of gut biota will have died off because you've starved them?
4: What are some good things to read on the need to have a diet that varies a lot? I have no concept of how much variation is necessary in order to ensure a good situation in terms of gut biota. I'm not really sure what variation even means; there are a million ways one could vary their diet and I don't know which forms of variation (e.g., is timing of nutrients important...like should you eat X for breakfast one day and for dinner the next day?) matter for health regarding gut biota.
5: Where can I find out how the duodenum works? I'm really confused. My impression (strange though it is) is that there's an "off-ramp" at the start of my gut (the "off-ramp" is the duodenum). And that sometimes the contents of a nutrient-supplement pill (or of a medication pill) will go 100% into my blood at the off-ramp and go no further. And that sometimes 0% of the contents of a nutrient-supplement pill (or of a medication pill) will go into my blood and the contents will instead continue forward into my gut and cause a bunch of activity in my gut.
6: I wonder how long a substance spends in the duodenum; is it possible to have a condition where substances spend too little time in the duodenum and just move through and miss the "off-ramp"? What's that condition called and how can it be treated? And if the substances spend adequate time in the duodenum, then what factors determine what % of something enters the blood and what % continues forward into the gut?
7: I do know that a strikingly low % of (e.g.) magnesium will absorb if you ingest a magnesium pill. That's what I thought I read, anyway. Not sure what factors cause that % to be so low.
8: It's obviously an extremely huge deal whether stuff enters your blood or instead feeds your gut biota, right? I mean, one needs to have some control over whether a substance continues forward into the gut (and thus feeds the gut biota), correct?
9: Does your body have any way to say "The gut and/or the gut biota really need this substances, so I'll close off the door to the blood and shunt this stuff into the gut"?
10: If the off-ramp is really good at absorbing stuff then won't 0% of a given substance get past? And won't the gut biota be starved when it comes to that substance?
11: It's probably a good thing if the gut biota are starved of particular substances, but you don't want to starve them of like every major nutrient, right?
12: So too much off-ramp efficiency would like wipe out your gut biota, right?
13: Why aren't all nutrient supplements (and all medications) that are intended to enter the blood just take under the tongue? Why send stuff into the gut if there are so many factors (gut-wise) that might prevent the substance from entering the blood? I do have a B12 supplement that's sublingual but I've never heard of lots of things (e.g., ADHD medications) being sublingual.
14: If someone were able to do so safely (like if they were a millionaire), would it be ideal to get nutrients and medications just injected into your veins?
15: Wouldn't getting things injected into your veins allow you to easily see the extent to which your gut and your gut biota were preventing proper absorption?
Last edited:
Michael Harrop
Active member
1. Random luck. See https://www.humanmicrobes.org/blog
3, 4. https://humanmicrobiome.info/diet/
5, 6. https://www.ecosia.org/search?q=how the duodenum works
https://humanmicrobiome.info/intestinal-permeability/
You should do web searches for most of your questions.
3, 4. https://humanmicrobiome.info/diet/
5, 6. https://www.ecosia.org/search?q=how the duodenum works
https://humanmicrobiome.info/intestinal-permeability/
You should do web searches for most of your questions.
OP
GutBrainAxis
Member
- Joined
- Oct 4, 2023
- Messages
- 80
- Thread Starter
- #60
Sorry for asking too many questions; I should see if I can get answers on Google before bugging you.
This product ( https://www.jamiesonvitamins.com/products/probiotic-regular-strength-5-billion) seemed to help me enormously regarding my psychiatric issues.
1: What do you make of the five strains included in the product? Are they all good ones?
2: Where should I look up each strain in order to see what it does and why it might be helping me so much?
3: Didn't you say that the standard way of talking about different types of gut biota is unhelpful because you have to be more specific? I'm curious about what you meant by that. I can see here on the product (that I asked about above) that it refers to "Lactococcus lactis (UALI-08)". So does "UALI-08" refer to some dimension that isn't normally referred to? I hope that all current research is specific about all important dimensions when it comes to gut biota; regarding gut biota, I hope that there aren't 1000s and 1000s of papers that are all useless because one or another dimension isn't included and therefore the research is too vague.
4: I found that adding more of the probiotic material made a difference. Or seemed to; there's no way to tell if something cumulative happened or whether increasing the dose induced a "breakthrough" somehow. Are there any studies on the issue of probiotic dosing? It's possible, I guess, that increasing the dose yields a qualitative improvement regarding the effect that the probiotic has. Maybe there's a threshold of dose past which a lot more of the probiotic material is able to "get a foothold" in your stomach and small intestine; maybe I experienced a "breakthrough" today because I boosted the dose past that threshold. It could be a physical thing having to do with whether the material can "stick" properly to your stomach wall or small-intestine wall. There's presumably literature on this matter of doses and thresholds and whether things "cling" properly.
5: I experienced a huge impact (from the probiotic product mentioned above) almost immediately. I didn't time things on a stopwatch, but it was just a couple hours I guess. Are such products supposed to have a big impact within a couple hours? Are such products supposed to take longer than 24 hours in order to have an impact?
6: I've been looking into whether I might have an infection. Not sure whether I can get my GP to look into that possibility, though, since I don't have any proof; it's just a hypothesis about what might be wrong with me, so my GP might not help me on this front. Is it possible that the probiotic stuff that helped me so much "displaced" this stuff ( https://en.wikipedia.org/wiki/Helicobacter_pylori ) from my stomach wall or small-intestine wall or something? I wonder if "displacement" could underlie the impact that I experiment from the probiotic.
7: Does Pepto Bismol just wipe out your stomach (and small-intestine) biota in general or does it only impact certain types of stomach biota and small-intestine biota? I wonder if Pepto Bismol "spares" good biota and only wipes out bad biota.
This product ( https://www.jamiesonvitamins.com/products/probiotic-regular-strength-5-billion) seemed to help me enormously regarding my psychiatric issues.
1: What do you make of the five strains included in the product? Are they all good ones?
2: Where should I look up each strain in order to see what it does and why it might be helping me so much?
3: Didn't you say that the standard way of talking about different types of gut biota is unhelpful because you have to be more specific? I'm curious about what you meant by that. I can see here on the product (that I asked about above) that it refers to "Lactococcus lactis (UALI-08)". So does "UALI-08" refer to some dimension that isn't normally referred to? I hope that all current research is specific about all important dimensions when it comes to gut biota; regarding gut biota, I hope that there aren't 1000s and 1000s of papers that are all useless because one or another dimension isn't included and therefore the research is too vague.
4: I found that adding more of the probiotic material made a difference. Or seemed to; there's no way to tell if something cumulative happened or whether increasing the dose induced a "breakthrough" somehow. Are there any studies on the issue of probiotic dosing? It's possible, I guess, that increasing the dose yields a qualitative improvement regarding the effect that the probiotic has. Maybe there's a threshold of dose past which a lot more of the probiotic material is able to "get a foothold" in your stomach and small intestine; maybe I experienced a "breakthrough" today because I boosted the dose past that threshold. It could be a physical thing having to do with whether the material can "stick" properly to your stomach wall or small-intestine wall. There's presumably literature on this matter of doses and thresholds and whether things "cling" properly.
5: I experienced a huge impact (from the probiotic product mentioned above) almost immediately. I didn't time things on a stopwatch, but it was just a couple hours I guess. Are such products supposed to have a big impact within a couple hours? Are such products supposed to take longer than 24 hours in order to have an impact?
6: I've been looking into whether I might have an infection. Not sure whether I can get my GP to look into that possibility, though, since I don't have any proof; it's just a hypothesis about what might be wrong with me, so my GP might not help me on this front. Is it possible that the probiotic stuff that helped me so much "displaced" this stuff ( https://en.wikipedia.org/wiki/Helicobacter_pylori ) from my stomach wall or small-intestine wall or something? I wonder if "displacement" could underlie the impact that I experiment from the probiotic.
7: Does Pepto Bismol just wipe out your stomach (and small-intestine) biota in general or does it only impact certain types of stomach biota and small-intestine biota? I wonder if Pepto Bismol "spares" good biota and only wipes out bad biota.
Michael Harrop
Active member
Do a web search.
That's the strain. https://humanmicrobiome.info/probiotic-guide
It can happen.
Sure.
https://humanmicrobiome.info/h-pylori/
OP
GutBrainAxis
Member
- Joined
- Oct 4, 2023
- Messages
- 80
- Thread Starter
- #62
What do you make of this paper?
I have no doubt that my own circadian systems are messed up. Not sure how to get my circadian systems back on track...this papers seems to point toward the idea that you have to fix your gut-biota composition in order to fix your circadian systems.
https://www.cell.com/cell-metabolism/pdf/S1550-4131(20)30067-X.pdf
There is growing evidence supporting not only an interaction, but also bidirectional communication between circadian rhythms and the gut microbiota. However, it is clear that the precise underpinnings of the mechanisms involved are still unknown. Although the majority of the data supporting their interaction is transitive and through an intermediary, these nodes of incorporation of the two systems are powerful, grouping into metabolism, the endocrine system, and the immune system. Unfortunately, thus far research has mostly only examined the effect of either circadian rhythm or gut microbiota/microbiota-gut-brain axis independently, but not together. There is a similar state of affairs regarding disease models: the current understanding mostly deals with metabolic diseases, the correlative conclusions of which demonstrate the cumulative effect of circadian rhythm dysfunction and gut microbiota alteration. Strong data linking circadian rhythm and gut microbiota dysfunction lie with their interactions with psychiatric illness and neurodegenerative disease. Here, there is a wealth of information examining diseases resulting from, or exacerbated by, interactions of the gut microbiota and circadian rhythm. Further, the examination into metabolic disorders is a crucial step in the right direction, and more work needs to be done to examine not only how both the microbiota-gut-brain axis and circadian rhythms influence disease, but also how they interplay with one another in the context of disease.
I have no doubt that my own circadian systems are messed up. Not sure how to get my circadian systems back on track...this papers seems to point toward the idea that you have to fix your gut-biota composition in order to fix your circadian systems.
https://www.cell.com/cell-metabolism/pdf/S1550-4131(20)30067-X.pdf
There is growing evidence supporting not only an interaction, but also bidirectional communication between circadian rhythms and the gut microbiota. However, it is clear that the precise underpinnings of the mechanisms involved are still unknown. Although the majority of the data supporting their interaction is transitive and through an intermediary, these nodes of incorporation of the two systems are powerful, grouping into metabolism, the endocrine system, and the immune system. Unfortunately, thus far research has mostly only examined the effect of either circadian rhythm or gut microbiota/microbiota-gut-brain axis independently, but not together. There is a similar state of affairs regarding disease models: the current understanding mostly deals with metabolic diseases, the correlative conclusions of which demonstrate the cumulative effect of circadian rhythm dysfunction and gut microbiota alteration. Strong data linking circadian rhythm and gut microbiota dysfunction lie with their interactions with psychiatric illness and neurodegenerative disease. Here, there is a wealth of information examining diseases resulting from, or exacerbated by, interactions of the gut microbiota and circadian rhythm. Further, the examination into metabolic disorders is a crucial step in the right direction, and more work needs to be done to examine not only how both the microbiota-gut-brain axis and circadian rhythms influence disease, but also how they interplay with one another in the context of disease.
Michael Harrop
Active member
OP
GutBrainAxis
Member
- Joined
- Oct 4, 2023
- Messages
- 80
- Thread Starter
- #64
I have really bad mental-health issues. The most important thing about my mental-health situation, I think, is how every single hour (it seems...I'm only being slightly hyperbolic) my consciousness changes to a new state. So there's extraordinary flux going on 24/7/365 in my consciousness.
1: Gut biota might underlie that flux; who knows, right?
2: We do in fact know that the gut biota are always in flux, correct? So maybe gut-biota flux underlies my consciousness flux.
3: What do you make of the below paper?
4: The paper gives a guide as to what someone with (e.g.) a bipolar diagnosis should do in order to improve their gut-biota situation, correct?
https://www.nature.com/articles/s41380-022-01456-3
This is the largest systematic literature review to date of gut microbiota composition across the major psychiatric conditions MDD, BD and SZ, comprising 56 comparison groups across 44 studies, and a total of 2510 psychiatric cases and 2407 controls. Our syntheses provide no strong evidence for a difference in the number or distribution of gut bacteria (α-diversity) in those with, compared to those without, a mental disorder. However, we did observe consistent differences in the overall composition of the gut microbiota (β-diversity) between cases and controls within each mental disorder category. In addition, we identified specific bacterial taxa with differential abundances between cases and controls, some of which were observed to be consistently different from controls across all three mental disorders. We identified substantial heterogeneity across studies in methodologies and reporting, including differences in study population inclusion and exclusion criteria, methods of gut microbiota stool sample collection, storage, processing and analysis, and consideration of, or adjustment for, key variables known to be associated with gut microbiota composition. Finally, we conducted a quality assessment of the included studies, the results of which highlight the need for guidelines on the conduct and reporting of microbiome-related research.
1: I thought that it was the case that very little lactate or lactic acid or whatever can actually cross the BBB. Do I have that correct? The paper talks about the dangers of lactate or lactic acid or whatever being produced, but I don't think that the paper ever says that this stuff crosses the BBB, though I could be confused.
2: Below is what the paper says about why the "bad" bacteria might be harmful:
https://www.nature.com/articles/s41380-022-01456-3
Our synthesis provided evidence of higher levels of lactic acid-producing bacteria across MDD, BD and SZ (Fig. 4). The genus Lactobacillus was higher in cases across all three of the major mental disorders. Similarly, higher abundances of other lactic acid producers were reported across disorders, including higher Enterococcus and Streptococcus in MDD and BD, higher and Escherichia/Shigella in MDD and SZ and higher Bifidobacterium in BD. These bacteria are generally considered beneficial to the host and can regulate metabolism, protect from pathogenic invasion, and have immunomodulatory effects [127, 128]. Lactic acid-producing bacteria also provide lactate for bacteria that use this molecule as a substrate to produce metabolites, such as the SCFA butyrate [129], in a process known as ‘cross-feeding’. However, there are some circumstances in which lactate production and utilisation may be detrimental to host health. Accumulation of lactate in the gut is potentially deleterious and associated with acidosis, cardiac arrhythmia and neurotoxicity [129, 130]. Many psychiatric disorders are associated with dysregulated mitochondrial energy generation, indexed by increased lactate and decreased pH (i.e. increased acidity) in the brain [131]. Increased faecal lactate is also associated with GI diseases such as short bowel disease and ulcerative colitis, whereas faecal lactate is seldom detected under normal conditions [129, 130]. Increased lactic acid production is a well described phenomenon in SZ and BD and is linked to mitochondrial dysfunction [132]. Lactate is also able to cross the blood brain barrier [133]; increased levels of lactic acid have been found in the brains of patients with MDD [134], and higher brain lactate levels have been observed in post-mortem brains of people with BD and SZ [131, 135]. We also observed higher abundances of bacterial genera that utilise lactate across studies, including Megasphaera in BD and SZ, and Escherichia/Shigella and Veillonella in SZ and MDD, which may indicate a compensatory mechanism in response to increased lactate production. Thus, we speculate that increased abundances of lactic acid-producing bacteria, such as those observed in this review, may influence mental disorder pathophysiology via lactate accumulation.
However, it should be noted that lactate has alternative metabolic fates, which further highlights the complex nature of the gut microbiome ecosystem and cross-feeding. For example, this systematic review also identified consistently higher abundances of Veillonella and Megasphaera in mental disorders. Species within these genera metabolise lactate to the SCFAs propionate and acetate while producing hydrogen [136]. Whilst propionate has been hypothesised to have antidepressant effects, excess propionate has been associated with increased depressive-like behaviours in animal studies [137] and elevated levels of propionate have been reported in Alzheimer’s disease [138]. In addition, it has been hypothesised that a by-product of lactate metabolism—hydrogen—may also influence host physiology [130, 139]. Hydrogen cross-feeding can occur with sulphate-reducing bacteria (SRB), methanogenic archaea, and acetogenic bacteria, which respectively produce hydrogen sulphide, methane and acetate [140]. Microorganisms that produce hydrogen sulphide (e.g. Desulfosporosinus, Desulfotomaculum, Desulfovibrio) and methane (e.g. Methanobrevibacter) have been reported to be in higher abundance in those with mental disorders [70, 81, 97, 102, 106, 112]. Functional pathways associated with methanogenesis, methane metabolism, and methane oxidation, have also been reported as enriched in mental disorders [66, 71, 95, 106]. Research investigating the influence of SRB and methanogens and their associated metabolites on health are inconsistent; both have been associated with both positive and negative health outcomes, but are hypothesised to be pro-inflammatory [140, 141]. Future studies employing metabolomics, alongside gut microbiome composition and functional analyses, are required to further our understanding of the potential role of the gut microbiome and lactate metabolism pathways in mental disorder pathophysiology.
Our trans-diagnostic approach identified lower levels of the butyrate-producing bacteria Coprococcus across all three mental disorders. Again, there was very little evidence to suggest this pattern was particularly associated with any specific disorder. Moreover, lower Faecalibacterium was a shared feature of MDD and BD, and lower Roseburia was a shared feature of BD and SZ; these bacteria are also butyrate producers. These findings are concordant with a Dutch study that identified Faecalibacterium and Coprococcus as positively correlated with quality-of-life scores in two large independent cohorts [115]. Coprococcus was also identified as lower in participants with general practitioner- or self-reported depression, even when controlling for the use of anti-depressants [115], which—like antipsychotics and anticonvulsants—have documented antimicrobial effects [142]. Similarly, a large US study reported positive associations between Coprococcus and Faecalibacterium and a ‘health-related’ group of host factors [143]. Lower Roseburia levels have been observed in epilepsy and post-traumatic stress disorder, however inconsistent findings have been observed for autism spectrum disorder and Parkinson’s disease [144]. Our findings are concordant with those observed across other mental disorders, which commonly report lower levels of faecal butyrate as well as reduced levels of butyrate-producing bacteria [144].
The potential role of butyrate-producing bacteria has been extensively studied [145, 146]. The production of butyrate and other SCFAs by host bacteria is primarily derived from the anaerobic fermentation of dietary fibre in the gut [147]. However, Roseburia species can produce butyrate via degradation of the mucin layer of the gut [148]. Butyrate is a SCFA understood to confer health benefits predominantly through influencing the immune system and intestinal homeostasis [149]. Butyrate is the primary source of energy for colon cells and plays an important role in maintaining gut barrier integrity. Butyrate receptors are also highly expressed throughout the body, especially on immune and endocrine cells [148]. Thus, it is possible that reduced butyrate production may contribute to the impaired gut barrier permeability and subsequent bacterial translocation into the systemic circulation, alongside systemic inflammation, that have been implicated [150] in, and observed [151] in mental disorders. Importantly, high fibre dietary interventions that have already demonstrated efficacy in improving outcomes in moderate to severe MDD [32] also increase butyrate-producing bacteria [152].
Our review also indicated that there were higher levels of bacteria associated with the metabolism of glutamate and γ-aminobutyric acid (GABA) across all three mental disorders. Again, there was very little evidence to suggest this pattern was particularly associated with any specific disorder, with higher Lactobacillus a common feature across all disorders. Higher abundances of Alistipes and Parabacteroides were a feature of MDD, higher Bifidobacterium a feature of BD, higher Enterococcus a feature of both MDD and BD and lower Bacteroides and Streptococcus a feature of SZ; these bacteria are associated with glutamate and GABA metabolism.
The previously mentioned lactic acid-producing bacteria Lactobacillus, Bifidobacterium and Enterococcus contain genes encoding glutamate decarboxylase (GAD) enzymes, which catalyse the reaction of L-glutamate to GABA [153, 154]. Eggerthella species are less commonly studied, however may also influence glutamate metabolism via GAD, and higher levels of Eggerthella have been associated with changes in glutamate metabolism in children with autism spectrum disorder [155]. In addition, Bacteroides, Escherichia and Parabacteroides have also been associated with GABA production [156]. It is possible that these gut bacteria observed in higher abundances across mental disorders may facilitate greater utilisation of glutamate (i.e. depletion) and increased synthesis of GABA.
The pathophysiological implications of differential abundances of specific bacteria remains to be confirmed. This highlights the need for multi-omics approaches to better understand the dynamic and complex functionality of the human gut microbiota. In addition, whether gut microbiota differences are the cause or consequence of pathophysiology, or are jointly influenced by shared risk factors such as diet, requires further exploration. Future longitudinal cohort studies will afford the documentation of changes in the gut microbiota and their relationship to disease development and may help to determine causality. Finally, intervention studies may help to further elucidate the mechanistic and biochemical implications of specific bacterial taxa on host health and disease.
1: How much does the fecal-transplantation thing tend to cost?
2: If you get the fecal-transplantation thing done but then you mess up your microbiota again then you're screwed, right? It seems like there would be unbelievable pressure to live an ultra-healthy lifestyle (regarding diet, exercise, etc., etc.). I'm not sure how resilient the new microbiota would be; normal people aren't plunged into horrifying dysbiosis whenever they're a bit unhealthy, so hopefully the patient who got the fecal-transplantation thing done wouldn't have to worry.
3: To what extent does the fecal-transplantation thing ever "stick"? The patient will have to eat extremely (!!!) carefully and exercise and do everything in a way that protects the new gut microbiota from any threats, correct? And furthermore, there might be genetic aspects of the patient that contributed to the patient having messed-up gut microbiota in the first place; these genetic threats will persist after the transplantation has been done, of course, so isn't that a major problem?
4: See below on the cost of the fecal-transplantation thing:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023044/
Recent studies have looked at the cost-effectiveness of FMT when compared to antibiotic drugs for the treatment of hospital-acquired C. difficile infection (CDI). One study in Canada used a Markov model to simulate a 65-year-old patient with second recurrence of mild-to-moderate CDI. They compared treatment options in areas with FMT programs and without an established program. After analysis and conversion to US dollars, outpatient vancomycin was $419.05 per course of treatment and fidaxomicin, brand name Dificid, was $1552.88 per course of treatment. FMT via capsule was $2097.39 [18]. Vancomycin and fidaxomicin are common first-line therapies for CDI and have a high potential for recurrence, which is shown in the study for probability of success in curing CDI. Vancomycin had a success rate of 0.556 and fidaxomicin had a success rate of 0.710, while FMT’s lowest success rate was 0.898 with capsule transmission of the healthy gut bacteria [18]. The total cost of FMT, including all aspects of treatment like screening and prep of the sample, was estimated at $3510.26 when compared to the use and prep of vancomycin and $3422.43 when compared to the use and prep of fidaxomicin. This cost is for FMT via colonoscopy, which was the highest cost estimated for FMT, and the number to treat to be comparable to antibiotics was 15 and 16, respectively. These costs seem to be more than what is currently available for patients and less cost-effective overall. One aspect to consider when comparing cost is hospitalization for patients with recurring CDI, which is a common occurrence with CDI after treatment with antibiotics. Hospitalization cost was checked during the study mentioned above. The cost for hospitalization due to mild-to-moderate recurrent CDI was $2688.94, $5252.99 for severe CDI that does not require a colectomy, and $17,082.18 for severe CDI that did require a colectomy [18]. Another U.S. study performed a similar study using a Markov model of a 67-year-old patient and found that success rates of vancomycin and fidaxomicin were higher at 0.846 and 0.800 for severe infections, respectively [19]. FMT may currently have higher costs that can be lowered over time, like screenings that are at a current cost of $883.60, but treatment of patients with pharmaceuticals that have less than 75% success rates may lead to worsening patient outcomes, increased mortality rates, and overall higher cost due to hospitalization of these patients [19].
1: Gut biota might underlie that flux; who knows, right?
2: We do in fact know that the gut biota are always in flux, correct? So maybe gut-biota flux underlies my consciousness flux.
3: What do you make of the below paper?
4: The paper gives a guide as to what someone with (e.g.) a bipolar diagnosis should do in order to improve their gut-biota situation, correct?
https://www.nature.com/articles/s41380-022-01456-3
This is the largest systematic literature review to date of gut microbiota composition across the major psychiatric conditions MDD, BD and SZ, comprising 56 comparison groups across 44 studies, and a total of 2510 psychiatric cases and 2407 controls. Our syntheses provide no strong evidence for a difference in the number or distribution of gut bacteria (α-diversity) in those with, compared to those without, a mental disorder. However, we did observe consistent differences in the overall composition of the gut microbiota (β-diversity) between cases and controls within each mental disorder category. In addition, we identified specific bacterial taxa with differential abundances between cases and controls, some of which were observed to be consistently different from controls across all three mental disorders. We identified substantial heterogeneity across studies in methodologies and reporting, including differences in study population inclusion and exclusion criteria, methods of gut microbiota stool sample collection, storage, processing and analysis, and consideration of, or adjustment for, key variables known to be associated with gut microbiota composition. Finally, we conducted a quality assessment of the included studies, the results of which highlight the need for guidelines on the conduct and reporting of microbiome-related research.
1: I thought that it was the case that very little lactate or lactic acid or whatever can actually cross the BBB. Do I have that correct? The paper talks about the dangers of lactate or lactic acid or whatever being produced, but I don't think that the paper ever says that this stuff crosses the BBB, though I could be confused.
2: Below is what the paper says about why the "bad" bacteria might be harmful:
https://www.nature.com/articles/s41380-022-01456-3
Our synthesis provided evidence of higher levels of lactic acid-producing bacteria across MDD, BD and SZ (Fig. 4). The genus Lactobacillus was higher in cases across all three of the major mental disorders. Similarly, higher abundances of other lactic acid producers were reported across disorders, including higher Enterococcus and Streptococcus in MDD and BD, higher and Escherichia/Shigella in MDD and SZ and higher Bifidobacterium in BD. These bacteria are generally considered beneficial to the host and can regulate metabolism, protect from pathogenic invasion, and have immunomodulatory effects [127, 128]. Lactic acid-producing bacteria also provide lactate for bacteria that use this molecule as a substrate to produce metabolites, such as the SCFA butyrate [129], in a process known as ‘cross-feeding’. However, there are some circumstances in which lactate production and utilisation may be detrimental to host health. Accumulation of lactate in the gut is potentially deleterious and associated with acidosis, cardiac arrhythmia and neurotoxicity [129, 130]. Many psychiatric disorders are associated with dysregulated mitochondrial energy generation, indexed by increased lactate and decreased pH (i.e. increased acidity) in the brain [131]. Increased faecal lactate is also associated with GI diseases such as short bowel disease and ulcerative colitis, whereas faecal lactate is seldom detected under normal conditions [129, 130]. Increased lactic acid production is a well described phenomenon in SZ and BD and is linked to mitochondrial dysfunction [132]. Lactate is also able to cross the blood brain barrier [133]; increased levels of lactic acid have been found in the brains of patients with MDD [134], and higher brain lactate levels have been observed in post-mortem brains of people with BD and SZ [131, 135]. We also observed higher abundances of bacterial genera that utilise lactate across studies, including Megasphaera in BD and SZ, and Escherichia/Shigella and Veillonella in SZ and MDD, which may indicate a compensatory mechanism in response to increased lactate production. Thus, we speculate that increased abundances of lactic acid-producing bacteria, such as those observed in this review, may influence mental disorder pathophysiology via lactate accumulation.
However, it should be noted that lactate has alternative metabolic fates, which further highlights the complex nature of the gut microbiome ecosystem and cross-feeding. For example, this systematic review also identified consistently higher abundances of Veillonella and Megasphaera in mental disorders. Species within these genera metabolise lactate to the SCFAs propionate and acetate while producing hydrogen [136]. Whilst propionate has been hypothesised to have antidepressant effects, excess propionate has been associated with increased depressive-like behaviours in animal studies [137] and elevated levels of propionate have been reported in Alzheimer’s disease [138]. In addition, it has been hypothesised that a by-product of lactate metabolism—hydrogen—may also influence host physiology [130, 139]. Hydrogen cross-feeding can occur with sulphate-reducing bacteria (SRB), methanogenic archaea, and acetogenic bacteria, which respectively produce hydrogen sulphide, methane and acetate [140]. Microorganisms that produce hydrogen sulphide (e.g. Desulfosporosinus, Desulfotomaculum, Desulfovibrio) and methane (e.g. Methanobrevibacter) have been reported to be in higher abundance in those with mental disorders [70, 81, 97, 102, 106, 112]. Functional pathways associated with methanogenesis, methane metabolism, and methane oxidation, have also been reported as enriched in mental disorders [66, 71, 95, 106]. Research investigating the influence of SRB and methanogens and their associated metabolites on health are inconsistent; both have been associated with both positive and negative health outcomes, but are hypothesised to be pro-inflammatory [140, 141]. Future studies employing metabolomics, alongside gut microbiome composition and functional analyses, are required to further our understanding of the potential role of the gut microbiome and lactate metabolism pathways in mental disorder pathophysiology.
Our trans-diagnostic approach identified lower levels of the butyrate-producing bacteria Coprococcus across all three mental disorders. Again, there was very little evidence to suggest this pattern was particularly associated with any specific disorder. Moreover, lower Faecalibacterium was a shared feature of MDD and BD, and lower Roseburia was a shared feature of BD and SZ; these bacteria are also butyrate producers. These findings are concordant with a Dutch study that identified Faecalibacterium and Coprococcus as positively correlated with quality-of-life scores in two large independent cohorts [115]. Coprococcus was also identified as lower in participants with general practitioner- or self-reported depression, even when controlling for the use of anti-depressants [115], which—like antipsychotics and anticonvulsants—have documented antimicrobial effects [142]. Similarly, a large US study reported positive associations between Coprococcus and Faecalibacterium and a ‘health-related’ group of host factors [143]. Lower Roseburia levels have been observed in epilepsy and post-traumatic stress disorder, however inconsistent findings have been observed for autism spectrum disorder and Parkinson’s disease [144]. Our findings are concordant with those observed across other mental disorders, which commonly report lower levels of faecal butyrate as well as reduced levels of butyrate-producing bacteria [144].
The potential role of butyrate-producing bacteria has been extensively studied [145, 146]. The production of butyrate and other SCFAs by host bacteria is primarily derived from the anaerobic fermentation of dietary fibre in the gut [147]. However, Roseburia species can produce butyrate via degradation of the mucin layer of the gut [148]. Butyrate is a SCFA understood to confer health benefits predominantly through influencing the immune system and intestinal homeostasis [149]. Butyrate is the primary source of energy for colon cells and plays an important role in maintaining gut barrier integrity. Butyrate receptors are also highly expressed throughout the body, especially on immune and endocrine cells [148]. Thus, it is possible that reduced butyrate production may contribute to the impaired gut barrier permeability and subsequent bacterial translocation into the systemic circulation, alongside systemic inflammation, that have been implicated [150] in, and observed [151] in mental disorders. Importantly, high fibre dietary interventions that have already demonstrated efficacy in improving outcomes in moderate to severe MDD [32] also increase butyrate-producing bacteria [152].
Our review also indicated that there were higher levels of bacteria associated with the metabolism of glutamate and γ-aminobutyric acid (GABA) across all three mental disorders. Again, there was very little evidence to suggest this pattern was particularly associated with any specific disorder, with higher Lactobacillus a common feature across all disorders. Higher abundances of Alistipes and Parabacteroides were a feature of MDD, higher Bifidobacterium a feature of BD, higher Enterococcus a feature of both MDD and BD and lower Bacteroides and Streptococcus a feature of SZ; these bacteria are associated with glutamate and GABA metabolism.
The previously mentioned lactic acid-producing bacteria Lactobacillus, Bifidobacterium and Enterococcus contain genes encoding glutamate decarboxylase (GAD) enzymes, which catalyse the reaction of L-glutamate to GABA [153, 154]. Eggerthella species are less commonly studied, however may also influence glutamate metabolism via GAD, and higher levels of Eggerthella have been associated with changes in glutamate metabolism in children with autism spectrum disorder [155]. In addition, Bacteroides, Escherichia and Parabacteroides have also been associated with GABA production [156]. It is possible that these gut bacteria observed in higher abundances across mental disorders may facilitate greater utilisation of glutamate (i.e. depletion) and increased synthesis of GABA.
The pathophysiological implications of differential abundances of specific bacteria remains to be confirmed. This highlights the need for multi-omics approaches to better understand the dynamic and complex functionality of the human gut microbiota. In addition, whether gut microbiota differences are the cause or consequence of pathophysiology, or are jointly influenced by shared risk factors such as diet, requires further exploration. Future longitudinal cohort studies will afford the documentation of changes in the gut microbiota and their relationship to disease development and may help to determine causality. Finally, intervention studies may help to further elucidate the mechanistic and biochemical implications of specific bacterial taxa on host health and disease.
1: How much does the fecal-transplantation thing tend to cost?
2: If you get the fecal-transplantation thing done but then you mess up your microbiota again then you're screwed, right? It seems like there would be unbelievable pressure to live an ultra-healthy lifestyle (regarding diet, exercise, etc., etc.). I'm not sure how resilient the new microbiota would be; normal people aren't plunged into horrifying dysbiosis whenever they're a bit unhealthy, so hopefully the patient who got the fecal-transplantation thing done wouldn't have to worry.
3: To what extent does the fecal-transplantation thing ever "stick"? The patient will have to eat extremely (!!!) carefully and exercise and do everything in a way that protects the new gut microbiota from any threats, correct? And furthermore, there might be genetic aspects of the patient that contributed to the patient having messed-up gut microbiota in the first place; these genetic threats will persist after the transplantation has been done, of course, so isn't that a major problem?
4: See below on the cost of the fecal-transplantation thing:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023044/
Recent studies have looked at the cost-effectiveness of FMT when compared to antibiotic drugs for the treatment of hospital-acquired C. difficile infection (CDI). One study in Canada used a Markov model to simulate a 65-year-old patient with second recurrence of mild-to-moderate CDI. They compared treatment options in areas with FMT programs and without an established program. After analysis and conversion to US dollars, outpatient vancomycin was $419.05 per course of treatment and fidaxomicin, brand name Dificid, was $1552.88 per course of treatment. FMT via capsule was $2097.39 [18]. Vancomycin and fidaxomicin are common first-line therapies for CDI and have a high potential for recurrence, which is shown in the study for probability of success in curing CDI. Vancomycin had a success rate of 0.556 and fidaxomicin had a success rate of 0.710, while FMT’s lowest success rate was 0.898 with capsule transmission of the healthy gut bacteria [18]. The total cost of FMT, including all aspects of treatment like screening and prep of the sample, was estimated at $3510.26 when compared to the use and prep of vancomycin and $3422.43 when compared to the use and prep of fidaxomicin. This cost is for FMT via colonoscopy, which was the highest cost estimated for FMT, and the number to treat to be comparable to antibiotics was 15 and 16, respectively. These costs seem to be more than what is currently available for patients and less cost-effective overall. One aspect to consider when comparing cost is hospitalization for patients with recurring CDI, which is a common occurrence with CDI after treatment with antibiotics. Hospitalization cost was checked during the study mentioned above. The cost for hospitalization due to mild-to-moderate recurrent CDI was $2688.94, $5252.99 for severe CDI that does not require a colectomy, and $17,082.18 for severe CDI that did require a colectomy [18]. Another U.S. study performed a similar study using a Markov model of a 67-year-old patient and found that success rates of vancomycin and fidaxomicin were higher at 0.846 and 0.800 for severe infections, respectively [19]. FMT may currently have higher costs that can be lowered over time, like screenings that are at a current cost of $883.60, but treatment of patients with pharmaceuticals that have less than 75% success rates may lead to worsening patient outcomes, increased mortality rates, and overall higher cost due to hospitalization of these patients [19].
Michael Harrop
Active member
There is plenty of evidence that it does.
To varying extents, yes.
That is not its purpose.
Depends where you get it https://humanmicrobiome.info/where-to-get-fmt.
You do it again.
It varies. https://humanmicrobiome.info/fmt/
Everyone should be doing that anyway.
Genetics are certainly important, and FMT may not be able to completely reverse developmental defects and deficiencies. This is why I've argued that the current ethos of childbearing is extremely unethical.
I agree with you completely. My opinion is that often highly trained specialists such as the mental health doctors do not follow fields outside of their limited profession and they simply do not understand the role that the microbiome plays on mental health. I started a company called MyGutly.com that provide personalized Autologous Fecal Transplantation. www.mygutly.com
PittsburghGutGuy
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Do what know what a super donor specimen would look like or are we just searching until we find something we then deem to be ideal?
If we know, why can we synthetically combine positive portions of different donors or "grow" what we want?
If we know, why can we synthetically combine positive portions of different donors or "grow" what we want?
Michael Harrop
Active member
It's not generally known, but I have a hypothesis. Yet even after screening a million applicants I haven't been able to find someone that meets the requirements...
Not currently. Knowledge and capabilities are too limited https://humanmicrobiome.info/testing.
OP
GutBrainAxis
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Hey Michael; I've been gone a long time...have you made any important progress regarding your own health issues?
My situation is weird. I'm going to do bloodwork regarding folate deficiency and B12 deficiency. I've had brief periods when taking those two nutrients where my brain and body were doing insanely well. Not sure if you yourself have also experienced those "miracle periods" where everything is going really well and it seems like the health problems are behind you.
I got an endoscopy. I was quite sure that I had H. pylori. I had ultra-fast and ultra-powerful reactions to:
--Pepto Bismol
--apple-cider vinegar
--a cocktail of cranberry, ginger, oregano, garlic, curcumin (I grabbed these things at the drugstore because Google said that each of them were useful against H. pylori...black pepper is also supposed to be useful against H. pylori but I haven't gotten that supplement yet)
The reactions are so fast that I assume (maybe wrongly) that these agents are taking action in my stomach and not in my small intestine.
The endoscopy didn't find any H. pylori. I guess there's some chance that they missed it, so I'll maybe try to get solid confirmation on that front.
I won't why I respond to those agents that I listed above. Could I have stomach dysbiosis that's not related to H. pylori? Could I have SIBO? Are these agents maybe impacting me for reasons that don't have to do with microbes of any sort?
I heard that there's an autoimmune stomach condition that mimics an H. pylori infection. And I guess that this autoimmune thing would respond to the agents that I listed above. Maybe the agents' antimicrobial properties are irrelevant.
I tried taking a probiotic tonight. Do you know any literature that explains what exactly the probiotic pill does when you take it? I felt a rapid effect but maybe that's unrelated to the probiotic pill. Does the pill just break apart and release a massive amount of bacteria into your stomach? And into your small intestine? Is there any scientific reason why that process would bring rapid improvement regarding gut issues and brain issues? Do the bacteria in the probiotic "crowd out" the "bad" microbes? To what extent is it known what the dynamics are (e.g., a "crowd-out-the-bad-microbes" dynamic) in terms of how the probiotic pills work?
I think that I want to enhance SCFA and butyrate production as much as possible. I will start taking my psyllium husk again.
Note that I seem to have issues regarding B12, folate, and iron. Those seeming deficiencies led me to think that I might have H. pylori. I have to be careful about the iron deficiency, though, since my iron pill contains a decent amount of folate; I need to get a 100%-iron pill that will allow me to see how I respond to 100% iron.
My situation is weird. I'm going to do bloodwork regarding folate deficiency and B12 deficiency. I've had brief periods when taking those two nutrients where my brain and body were doing insanely well. Not sure if you yourself have also experienced those "miracle periods" where everything is going really well and it seems like the health problems are behind you.
I got an endoscopy. I was quite sure that I had H. pylori. I had ultra-fast and ultra-powerful reactions to:
--Pepto Bismol
--apple-cider vinegar
--a cocktail of cranberry, ginger, oregano, garlic, curcumin (I grabbed these things at the drugstore because Google said that each of them were useful against H. pylori...black pepper is also supposed to be useful against H. pylori but I haven't gotten that supplement yet)
The reactions are so fast that I assume (maybe wrongly) that these agents are taking action in my stomach and not in my small intestine.
The endoscopy didn't find any H. pylori. I guess there's some chance that they missed it, so I'll maybe try to get solid confirmation on that front.
I won't why I respond to those agents that I listed above. Could I have stomach dysbiosis that's not related to H. pylori? Could I have SIBO? Are these agents maybe impacting me for reasons that don't have to do with microbes of any sort?
I heard that there's an autoimmune stomach condition that mimics an H. pylori infection. And I guess that this autoimmune thing would respond to the agents that I listed above. Maybe the agents' antimicrobial properties are irrelevant.
I tried taking a probiotic tonight. Do you know any literature that explains what exactly the probiotic pill does when you take it? I felt a rapid effect but maybe that's unrelated to the probiotic pill. Does the pill just break apart and release a massive amount of bacteria into your stomach? And into your small intestine? Is there any scientific reason why that process would bring rapid improvement regarding gut issues and brain issues? Do the bacteria in the probiotic "crowd out" the "bad" microbes? To what extent is it known what the dynamics are (e.g., a "crowd-out-the-bad-microbes" dynamic) in terms of how the probiotic pills work?
I think that I want to enhance SCFA and butyrate production as much as possible. I will start taking my psyllium husk again.
Note that I seem to have issues regarding B12, folate, and iron. Those seeming deficiencies led me to think that I might have H. pylori. I have to be careful about the iron deficiency, though, since my iron pill contains a decent amount of folate; I need to get a 100%-iron pill that will allow me to see how I respond to 100% iron.
OP
GutBrainAxis
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I have this really weird symptom; see below my description. Do you know how I could somehow get to the bottom of what this is? Just today my stomach (or something close to it) was "pulsing" a couple times and the "crackling" sensation seemed to go along with those pulsations. There seems to be some link from my stomach (or something close to it) and my brain. Sometimes it feels like there's a "wire" (a nerve, I guess) from my stomach (or something close to it) to my brain...and feels like there's some "crackling" sensation moving up that "wire". This symptom could be meaningless or could be an extremely valuable clue.
There's a particular phenomenon that I experience that might be unimportant but seems to be related to my gastrointestinal system. It's a very strange phenomenon; I wonder whether it might (who knows?) actually be relevant. I would be very grateful if I could tell you about it; it could be meaningless or it could actually allow for illumination of what's going on inside my body. Let me know what you think.
Basically it's a "fizzy" or "popping" or "crispy" or "crackling" sensation. Sometimes I get the impression (this is just a mere impression; nothing scientific) that there's some nerve that goes from my stomach up to my brain that "crackles". Some people online are probably referring to the same phenomenon when they talk about the "pop rocks" sensation (https://en.wikipedia.org/wiki/Pop_Rocks), though it's unclear to me if they're talking about the same thing that I'm talking about. And I also get this same sensation in the back of my neck when (e.g.) I take a folate supplement. The sensation has nothing to do with motion; it occurs when I'm completely still. When it happens in the back of the neck, I get the sensation that something is passing into my brain or across my "blood/brain barrier".
I know that it sounds odd, but I wonder if it relates to nitric oxide? I heard that when you crack your fingers that's related to some gas being compressed into a small space or something? Not sure what causes one's fingers to crack.
There's a particular phenomenon that I experience that might be unimportant but seems to be related to my gastrointestinal system. It's a very strange phenomenon; I wonder whether it might (who knows?) actually be relevant. I would be very grateful if I could tell you about it; it could be meaningless or it could actually allow for illumination of what's going on inside my body. Let me know what you think.
Basically it's a "fizzy" or "popping" or "crispy" or "crackling" sensation. Sometimes I get the impression (this is just a mere impression; nothing scientific) that there's some nerve that goes from my stomach up to my brain that "crackles". Some people online are probably referring to the same phenomenon when they talk about the "pop rocks" sensation (https://en.wikipedia.org/wiki/Pop_Rocks), though it's unclear to me if they're talking about the same thing that I'm talking about. And I also get this same sensation in the back of my neck when (e.g.) I take a folate supplement. The sensation has nothing to do with motion; it occurs when I'm completely still. When it happens in the back of the neck, I get the sensation that something is passing into my brain or across my "blood/brain barrier".
I know that it sounds odd, but I wonder if it relates to nitric oxide? I heard that when you crack your fingers that's related to some gas being compressed into a small space or something? Not sure what causes one's fingers to crack.
OP
GutBrainAxis
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Should one actually be concerned about stomach microbes if H. pylori has been ruled out? I mean, see below a paper from 2015...not the newest paper...it talks about stomach microbes.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616220/
Thick mucus layer, acidic gastric juice and peristaltic movement in the stomach have raised the dogma that “the stomach is a sterile organ”. However, the dogma quickly changes after the discovery of Campylobacter pyloridis in 1982, which is renamed into H. pylori in 1984[11]. H. pylori can colonise the stomach by producing urease to survive under acidic condition. Soon after the discovery of H. pylori, another type of bacteria such as Vellomella, Lactobacillus and Clostridium are found as transient bacteria that reside in the stomach[12]. However, the ability of the transient bacteria to crosslink with the host and penetrate the mucosa layer is drawing people’s attention.
Recently, the development of culture-independent molecular technologies based on 16s rRNA has revealed that five abundant genera microbiota other than H. pylori reside in the stomach. They are Neisseria, Haemophilus, Prevotella, Streptococcus, and Porphyromonas[13-16].
Dysbiosis of the gastric microbiota has been implicated in immune system regulation and enhancing disease symptoms. Several researchers showed the gastric microbiota arose from patients infected with H. pylori are different from uninfected people[17,18]. Osaki et al[19] also described the prolonged exposure to H. pylori infection has altered the composition of the microbiota in rodent stomachs. These findings suggested an interaction between H. pylori and the gastric microbial community[8]. Though the mechanism of H. pylori in altering the gastric microbiota remains unclear, possible explanation is that the induction of host antimicrobial peptides, such as β-defensin 2[20] or cecropin-like peptide, may directly kill another microbiota[21].
All of these findings had shed a light that dysbiosis of gastric microbiota might related to the susceptibility to gastric inflammation and tumorigenicity in patients with H. pylori infection. H. pylori infection also initiate the inflammatory cascades that induce physiological changes that reduces the gastric secretion from parietal cells and elevation of pH in the stomach. The elevation of pH eventually resulted in the colonisation of another microrganisms in the stomach[22-25]. Engstrand et al[26] reported that gastric cancer development may related to the alteration of gastric microbiota. The commensal microbes can communicate with dysbiotic pathogens such as Salmonella typhimurium that have the ability to alter gastrointestinal homeostasis to pathogenic inflammation. However, it should be further investigated whether infections with commensals are associated with the susceptibility to gastric inflammation and tumorigenicity in patients with H. pylori infection.
...
It has been proven recently that not only long-term dietary intake, but also short-term dietary intake alters human gut microbiome[73]. The animal-based diet significantly increased the levels of fecal deoxycholic concentrations, which is the product of microbial metabolism and promotes liver cancer[74]. Moreover, the animal-based diet significantly increased sulphite-reducing bacteria which might increase inflammation to intestinal tissue through H2S production[75].
Human disease can also be developed from an imbalance between commensal bacteria and fungi[76]. Candida albicans (C. albicans) extensively distributes on human skin and mucosal surfaces, such as the oral cavity, the gastrointestinal tract, and the lower female reproductive tract. Because of this, the fungus is most frequently implicated in mixed bacterial-fungal infections. Enhancement of bacterial virulence by C. albicans has been described in studies assessing the virulence of mixed C. albicans and Staphylococcus aureus infection in mice[77].
Bacteria, virus, fungus, and some parasites are affecting each other to reside and propagate in human alimentary tract. Their opportunistic imbalance often provides illness to human beings. Our body had better keep benign microbiota and refrain from having dysbiotic microbiota. Though little in known, further investigation will surely tell us the way how to keep symbiotic relation with gastric microbiota.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616220/
Thick mucus layer, acidic gastric juice and peristaltic movement in the stomach have raised the dogma that “the stomach is a sterile organ”. However, the dogma quickly changes after the discovery of Campylobacter pyloridis in 1982, which is renamed into H. pylori in 1984[11]. H. pylori can colonise the stomach by producing urease to survive under acidic condition. Soon after the discovery of H. pylori, another type of bacteria such as Vellomella, Lactobacillus and Clostridium are found as transient bacteria that reside in the stomach[12]. However, the ability of the transient bacteria to crosslink with the host and penetrate the mucosa layer is drawing people’s attention.
Recently, the development of culture-independent molecular technologies based on 16s rRNA has revealed that five abundant genera microbiota other than H. pylori reside in the stomach. They are Neisseria, Haemophilus, Prevotella, Streptococcus, and Porphyromonas[13-16].
Dysbiosis of the gastric microbiota has been implicated in immune system regulation and enhancing disease symptoms. Several researchers showed the gastric microbiota arose from patients infected with H. pylori are different from uninfected people[17,18]. Osaki et al[19] also described the prolonged exposure to H. pylori infection has altered the composition of the microbiota in rodent stomachs. These findings suggested an interaction between H. pylori and the gastric microbial community[8]. Though the mechanism of H. pylori in altering the gastric microbiota remains unclear, possible explanation is that the induction of host antimicrobial peptides, such as β-defensin 2[20] or cecropin-like peptide, may directly kill another microbiota[21].
All of these findings had shed a light that dysbiosis of gastric microbiota might related to the susceptibility to gastric inflammation and tumorigenicity in patients with H. pylori infection. H. pylori infection also initiate the inflammatory cascades that induce physiological changes that reduces the gastric secretion from parietal cells and elevation of pH in the stomach. The elevation of pH eventually resulted in the colonisation of another microrganisms in the stomach[22-25]. Engstrand et al[26] reported that gastric cancer development may related to the alteration of gastric microbiota. The commensal microbes can communicate with dysbiotic pathogens such as Salmonella typhimurium that have the ability to alter gastrointestinal homeostasis to pathogenic inflammation. However, it should be further investigated whether infections with commensals are associated with the susceptibility to gastric inflammation and tumorigenicity in patients with H. pylori infection.
...
It has been proven recently that not only long-term dietary intake, but also short-term dietary intake alters human gut microbiome[73]. The animal-based diet significantly increased the levels of fecal deoxycholic concentrations, which is the product of microbial metabolism and promotes liver cancer[74]. Moreover, the animal-based diet significantly increased sulphite-reducing bacteria which might increase inflammation to intestinal tissue through H2S production[75].
Human disease can also be developed from an imbalance between commensal bacteria and fungi[76]. Candida albicans (C. albicans) extensively distributes on human skin and mucosal surfaces, such as the oral cavity, the gastrointestinal tract, and the lower female reproductive tract. Because of this, the fungus is most frequently implicated in mixed bacterial-fungal infections. Enhancement of bacterial virulence by C. albicans has been described in studies assessing the virulence of mixed C. albicans and Staphylococcus aureus infection in mice[77].
Bacteria, virus, fungus, and some parasites are affecting each other to reside and propagate in human alimentary tract. Their opportunistic imbalance often provides illness to human beings. Our body had better keep benign microbiota and refrain from having dysbiotic microbiota. Though little in known, further investigation will surely tell us the way how to keep symbiotic relation with gastric microbiota.
OP
GutBrainAxis
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- #72
Have you ever gotten your blood's "inflammatory profile" checked? I'm curious because it seems like one could get some genuinely valuable data from looking at one's cytokine levels.
I understand that it might be expensive and that it wouldn't magically tell you exactly what's wrong with you. But I think that it could be an important method of investigation.
I understand that it might be expensive and that it wouldn't magically tell you exactly what's wrong with you. But I think that it could be an important method of investigation.
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OP
GutBrainAxis
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I took some psyllium husk and it had a profound effect on my mind. Just like (sometimes) apple-cider vinegar has had a profound effect on my mind.
It's not normal for things to go into your GI system and then have a profound impact on your brain. Do I have SIBO? Do I have something going on with my stomach?
I experienced a brief period where my digestion was actually good. There were vibrations and secretions; I could really properly extract nourishment from foods (even from foods that I normally find very hard-to-digest). My bowel movements were qualitatively healthier than at any other time in my life (as far as I know). But that period of wonderful functioning ended. I need to get it back.
I guess that I could look at the things that impact my brain and ask "By what mechanism could these particular substances exert an impact?". Asking that might lead me toward a successful diagnosis of what's wrong with me. For example, how might psyllium husk exert a major impact on my brain?
Regarding the psyllium husk, I can actually feel movement in what I assume is my small intestine; presumably that's the psyllium husk actually moving through my small intestine.
It's not normal for things to go into your GI system and then have a profound impact on your brain. Do I have SIBO? Do I have something going on with my stomach?
I experienced a brief period where my digestion was actually good. There were vibrations and secretions; I could really properly extract nourishment from foods (even from foods that I normally find very hard-to-digest). My bowel movements were qualitatively healthier than at any other time in my life (as far as I know). But that period of wonderful functioning ended. I need to get it back.
I guess that I could look at the things that impact my brain and ask "By what mechanism could these particular substances exert an impact?". Asking that might lead me toward a successful diagnosis of what's wrong with me. For example, how might psyllium husk exert a major impact on my brain?
Regarding the psyllium husk, I can actually feel movement in what I assume is my small intestine; presumably that's the psyllium husk actually moving through my small intestine.
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OP
GutBrainAxis
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This seems like a really good review: https://www.annualreviews.org/content/journals/10.1146/annurev-med-042320-014032.
Why do I get the sense that my problems are "bottom-up"? It's interesting how I have that sense. The review says that there's "top-down" causation too; not sure why I have the sense that it's "bottom-up".
Why do I get the sense that my problems are "bottom-up"? It's interesting how I have that sense. The review says that there's "top-down" causation too; not sure why I have the sense that it's "bottom-up".
OP
GutBrainAxis
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It really freaks me out how I can't find a single (!!!) mention in the literature of a patient who goes through extreme flux of the sort that I live with. It's just downright weird how I took some psyllium husk and then my entire consciousness changed; that's weird. You'd think that there'd be some literature on this extreme-flux phenomenon that I experience.
It truly bothers me that I haven't seen one word about this in the literature. Surely I'm not the only one on this planet who experiences this phenomenon. Every day I exist within a different mental state. And I even undergo intra-day changes regarding my consciousness. It's not a mood thing; it's something else.
It truly bothers me that I haven't seen one word about this in the literature. Surely I'm not the only one on this planet who experiences this phenomenon. Every day I exist within a different mental state. And I even undergo intra-day changes regarding my consciousness. It's not a mood thing; it's something else.
OP
GutBrainAxis
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What do you think of this?
https://www.annualreviews.org/content/journals/10.1146/annurev-med-042320-014032
The effects of enteric microbial manipulations in controlled clinical trials in patients with depression and/or IBS have been evaluated with probiotics, antibiotics, and the low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet (70). Several studies have demonstrated the effectiveness of a low-FODMAP diet in the short-term treatment of IBS symptoms (71, 72), and diet-induced changes in the gut microbiome (73) have been implicated as an underlying mechanism. The low-FODMAP diet results in decreased production of gas and osmotically active microbial metabolites as a result of decreased microbial fermentation. This reduction in microbial gas production in a hypersensitive gut is thought to lead to improvements in the perception of bloating, flatulence, and pain (74). In line with this theory, several randomized controlled trials (RCTs) in adults have demonstrated that intake of a low-FODMAP diet improves IBS symptoms, regardless of subtype, as well as health-related quality of life, anxiety, and activity impairment in adults with IBS (74). However, even though these results seem to support a role for the gut microbiome in some IBS symptoms, and despite the finding that the low-FODMAP diet appears to be useful for short-term treatment of some IBS symptoms, such a diet is not recommended as long-term treatment for IBS patients. Long-term compliance is low, and the long-term reduction of complex carbohydrates in the diet is associated with a decrease of gut microbial diversity and richness, particularly of butyrate-producing strains, an effect with well-known negative consequences on gut health. To avoid these long-term problems, patients are recommended to selectively reintroduce eliminated food items following a course of treatment with the low-FODMAP diet. There is limited evidence for the effectiveness of a ketogenic diet in treating IBS, but the evidence is weak, and similar to the low-FODMAP diet, in a ketogenic diet the elimination of complex carbohydrates is inconsistent with current beliefs about the benefits of a largely plant-based diet on gut health and gut immune function. An alternative approach is to have IBS patients start with a Mediterranean-type diet with its general health benefits, encourage them to keep a food diary, and ask them to identify food items that reproducibly and consistently worsen their symptoms. Food items thus implicated may differ between patients, but once such items have been identified by a patient, a reduction in intake or elimination of the item is recommended. The result is a personalized diet with well-documented health benefits that does not compromise gut microbial health. Encouraging the patient to tailor their own personal diet provides them with an increased sense of control (self-efficacy) and reduced symptom-related anxiety.
https://www.annualreviews.org/content/journals/10.1146/annurev-med-042320-014032
The effects of enteric microbial manipulations in controlled clinical trials in patients with depression and/or IBS have been evaluated with probiotics, antibiotics, and the low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet (70). Several studies have demonstrated the effectiveness of a low-FODMAP diet in the short-term treatment of IBS symptoms (71, 72), and diet-induced changes in the gut microbiome (73) have been implicated as an underlying mechanism. The low-FODMAP diet results in decreased production of gas and osmotically active microbial metabolites as a result of decreased microbial fermentation. This reduction in microbial gas production in a hypersensitive gut is thought to lead to improvements in the perception of bloating, flatulence, and pain (74). In line with this theory, several randomized controlled trials (RCTs) in adults have demonstrated that intake of a low-FODMAP diet improves IBS symptoms, regardless of subtype, as well as health-related quality of life, anxiety, and activity impairment in adults with IBS (74). However, even though these results seem to support a role for the gut microbiome in some IBS symptoms, and despite the finding that the low-FODMAP diet appears to be useful for short-term treatment of some IBS symptoms, such a diet is not recommended as long-term treatment for IBS patients. Long-term compliance is low, and the long-term reduction of complex carbohydrates in the diet is associated with a decrease of gut microbial diversity and richness, particularly of butyrate-producing strains, an effect with well-known negative consequences on gut health. To avoid these long-term problems, patients are recommended to selectively reintroduce eliminated food items following a course of treatment with the low-FODMAP diet. There is limited evidence for the effectiveness of a ketogenic diet in treating IBS, but the evidence is weak, and similar to the low-FODMAP diet, in a ketogenic diet the elimination of complex carbohydrates is inconsistent with current beliefs about the benefits of a largely plant-based diet on gut health and gut immune function. An alternative approach is to have IBS patients start with a Mediterranean-type diet with its general health benefits, encourage them to keep a food diary, and ask them to identify food items that reproducibly and consistently worsen their symptoms. Food items thus implicated may differ between patients, but once such items have been identified by a patient, a reduction in intake or elimination of the item is recommended. The result is a personalized diet with well-documented health benefits that does not compromise gut microbial health. Encouraging the patient to tailor their own personal diet provides them with an increased sense of control (self-efficacy) and reduced symptom-related anxiety.
OP
GutBrainAxis
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I had an extremely good response to this:
https://www.jamiesonvitamins.com/products/probiotic-ultra-strength-60-billion
Lactobacillus paracasei (HA-196) 21.6 CFU
Lactobacillus paracasei (R0215) 21.3 CFU
Bifidobacterium breve (HA-129) 8.7 CFU
Lactobacillus plantarum (R1012) 4.2 CFU
Bifidobacterium longum subsp. longum (HA-135) 3.0 CFU
Lactobacillus rhamnosus (HA-111) 0.75 CFU
Lactobacillus helveticus (HA-122) 0.15 CFU
Bifidobacterium animalis subsp. lactis (HA-194) 0.15 CFU
Bifidobacterium bifidum (HA-132) 0.15 CFU
I also have this product:
https://www.alignprobiotics.com/en-us/products/probiotics-digestive-support/probiotic-supplement
Contains Bifidobacterium 35624™
The unique probiotic strain, Bifidobacterium 35624™, was developed by gastroenterologists to help relieve occasional bloating, gas, and abdominal discomfort*
1: Which probiotics do you yourself take?
2: How can a probiotic capsule sometimes take action very rapidly (like within 5 minutes? maybe faster) in my body? Not sure the mechanisms involved.
3: Do probiotic capsules' contents replace/displace "bad" microbes? Or do probiotic capsules' contents "fill a void"? Or...? Not sure the mechanisms at play.
4: Suppose you play around with probiotics for a long time. What is the barrier to success? Is the barrier that you can't displace/replace the incumbent microbes?
5: If people could sterilize their whole gut and then just take a bunch of probiotics, would people achieve success at a very high rate? And what would account for a non-100% success rate if people were sterilizing their whole gut first?
https://www.jamiesonvitamins.com/products/probiotic-ultra-strength-60-billion
Lactobacillus paracasei (HA-196) 21.6 CFU
Lactobacillus paracasei (R0215) 21.3 CFU
Bifidobacterium breve (HA-129) 8.7 CFU
Lactobacillus plantarum (R1012) 4.2 CFU
Bifidobacterium longum subsp. longum (HA-135) 3.0 CFU
Lactobacillus rhamnosus (HA-111) 0.75 CFU
Lactobacillus helveticus (HA-122) 0.15 CFU
Bifidobacterium animalis subsp. lactis (HA-194) 0.15 CFU
Bifidobacterium bifidum (HA-132) 0.15 CFU
I also have this product:
https://www.alignprobiotics.com/en-us/products/probiotics-digestive-support/probiotic-supplement
Contains Bifidobacterium 35624™
The unique probiotic strain, Bifidobacterium 35624™, was developed by gastroenterologists to help relieve occasional bloating, gas, and abdominal discomfort*
1: Which probiotics do you yourself take?
2: How can a probiotic capsule sometimes take action very rapidly (like within 5 minutes? maybe faster) in my body? Not sure the mechanisms involved.
3: Do probiotic capsules' contents replace/displace "bad" microbes? Or do probiotic capsules' contents "fill a void"? Or...? Not sure the mechanisms at play.
4: Suppose you play around with probiotics for a long time. What is the barrier to success? Is the barrier that you can't displace/replace the incumbent microbes?
5: If people could sterilize their whole gut and then just take a bunch of probiotics, would people achieve success at a very high rate? And what would account for a non-100% success rate if people were sterilizing their whole gut first?
Michael Harrop
Active member
No, I still haven't found a donor who meets the ideal criteria.
No. https://humanmicrobiome.info/sibo/
Almost certainly not. The scientific literature has shown that the effects of many drugs, xenobiotics, etc. largely come from their impact on the gut microbiome.
It does many things. https://humanmicrobiome.info/probiotics/
Other than the probiotics page, you may want to review the "mechanisms" section here https://humanmicrobiome.info/intro/#mechanisms.
You may also want to review the "Functions" section of the wiki.
Since the gut microbiome impacts the entire body, the range of possible symptoms is vast. There are not good targeted treatments, which is why FMT is the primary intervention.
You should be concerned about the entire gut microbiome.
FMT, donor-matching, screening for specific microbes, and pre-treatment/eradication. "Killing things off" vs suppression & ecosystem restoration.
Have you read my FMT experiences summary?
1, 4. None currently. https://humanmicrobiome.info/probiotic-guide/
2-3. See previous citations. Many mechanisms.
5. Not even close. See probiotic guide above.
OP
GutBrainAxis
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Michael, what's been your response to this combination:
--lots of apple-cider vinegar (this is the main agent)
--Pepto Bismol (a little bit)
--NAC (the supplement, I mean...it has impacts on microbiota...it has impacts on various things)
--the following cocktail of extracts: ginger, cranberry, garlic, oregano, green tea, curcumin
The above things (ACV, Pepto, NAC, and the cocktail) have been life-changing for me.
ACV has been the main game-changing agent for me. The problem is, I'm not sure what it does or even what it is (apart from acetic acid) chemically. I only know about this:
https://www.nature.com/articles/s41598-017-18618-x
https://www.nature.com/articles/s41598-020-78407-x
--lots of apple-cider vinegar (this is the main agent)
--Pepto Bismol (a little bit)
--NAC (the supplement, I mean...it has impacts on microbiota...it has impacts on various things)
--the following cocktail of extracts: ginger, cranberry, garlic, oregano, green tea, curcumin
The above things (ACV, Pepto, NAC, and the cocktail) have been life-changing for me.
ACV has been the main game-changing agent for me. The problem is, I'm not sure what it does or even what it is (apart from acetic acid) chemically. I only know about this:
https://www.nature.com/articles/s41598-017-18618-x
And about this:
https://www.nature.com/articles/s41598-020-78407-x
Michael Harrop
Active member
ACV and the spices have not been helpful for me. I haven't tried the other two.
OP
GutBrainAxis
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- #81
Have you tried everything that I mentioned in combination? I wonder whether doing so can make all the difference; if you try things individually then the effect might not be significant at all.
Michael Harrop
Active member
I haven't. I'm very doubtful that is the solution.
OP
GutBrainAxis
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- #83
1: Do you know any papers on gastric dysbiosis? And on how important gastric dysbiosis can be?
2: Do you know any information (or papers) on how one can find out if one has gastric dysbiosis? And on what treatments are possible?
I know that this is a somewhat random (maybe?) question, but do you know any papers on the full range of mechanisms by which a duodenal ulcer (I have one) might have body-wide impacts and brain impacts?
If the duodenal ulcer prevents absorption of nutrients (to what extent can this happen?) then that would have a body-wide impact and a brain impact. But can the duodenal ulcer also have such impacts through some sort of inflammatory mechanism(s)?
2: Do you know any information (or papers) on how one can find out if one has gastric dysbiosis? And on what treatments are possible?
I know that this is a somewhat random (maybe?) question, but do you know any papers on the full range of mechanisms by which a duodenal ulcer (I have one) might have body-wide impacts and brain impacts?
If the duodenal ulcer prevents absorption of nutrients (to what extent can this happen?) then that would have a body-wide impact and a brain impact. But can the duodenal ulcer also have such impacts through some sort of inflammatory mechanism(s)?
Michael Harrop
Active member
Why do you think "gastric" is separate from the rest of the gut microbiome? I already answered the treatment questions.
You'll have to search pubmed or google scholar for specific papers.
You'll have to search pubmed or google scholar for specific papers.
OP
GutBrainAxis
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What information/papers do you know of regarding the connection between gastric microbiota and intestinal microbiota?
I thought they were separate. See here a paper that I just found randomly:
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006573
Drivers of susceptibility to gastric carcinogenesis include H. pylori strain-specific virulence determinants, host constituents, and environmental factors. Along with these elements, the microbiota of the stomach may also influence the development of gastric malignancies. The acidic environment of the stomach in conjunction with low levels of cultured bacteria from this site previously led to assumptions that the gastric niche was not able to support a diverse microbial community. However, recent advances in DNA sequencing of conserved ribosomal RNA genes, phylogenetic analyses, and computational methods have uncovered a complex microbiota within the human stomach with the potential for disease induction [2].
...
A first step in establishing causation is to take inventory of a particular resident microbial population, and several investigations have focused on defining microbial communities within the human stomach and the interactions of these populations with H. pylori (Fig 1A). Numerous groups have used PCR- and sequencing-based approaches to demonstrate that H. pylori-negative individuals harbor a highly diverse gastric microbiota dominated by 5 predominant phyla: Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria [13–15]. In contrast, among H. pylori-positive subjects, H. pylori is the single most abundant bacterium present in the stomach and accounts for between 72% and 97% of all sequence reads [13, 14].
...
Most bacteria cannot survive in the acidic environment of the stomach. However, it has been well established that, in a subset of persons, infection with H. pylori leads to achlorhydria and decreased acid secretion. Thus, long-term H. pylori colonization and neutralization of the gastric environment may directly contribute to alterations in the gastric microbiota. There are also clinical studies that support this concept, namely that patients treated with acid-suppressive drugs, such as proton pump inhibitors, exhibit a significant increase in the burden of non-H. pylori bacteria within the stomach. Of interest, this increase correlates with increased inflammatory responses, suggesting that non-H. pylori bacteria that colonize an achlorhydric stomach may have the capacity to promote inflammation that could potentially facilitate the progression to cancer [22, 23]. However, definitive evidence for this requires careful interventional studies that have yet to be performed.
...
In addition to the stomach, bacteria within other microbial niches may exert a role in modulating H. pylori-induced gastric inflammatory responses. Two studies have shown that precolonization with intestinal Helicobacters (H. bilis, H. hepaticus, and H. muridarum) can either increase or decrease the severity of gastric inflammation induced by H. pylori by altering T-regulatory cell responses [30, 31]. Another study demonstrated that H. pylori per se is present within the intestine in a coccoid form and that the interaction between phagocytes and H. pylori within intestinal Peyer’s patches plays a critical role in modifying the intensity of H. pylori-induced gastritis [32]. However, other studies have shown that the microflora within the stomach can accelerate the progression of gastric cancer in the presence of H. pylori and do so with no differences detected in the composition of the intestinal microbiota [27, 28]. Addressing whether the resident intestinal microbiome directly contributes to the pathophysiology of H. pylori-induced gastric diseases is an avenue that requires further investigation, and it is important to consider that the effects of bacteria and microbial communities in the intestine and the stomach on gastric pathophysiology may not be mutually exclusive.
...
Evidence that the host microbiota specifically functions to promote health and prevent disease and that dysbiosis contributes to inflammation, susceptibility to pathogens, and diseases (including cancer) is undisputed [3]. As a result, the concept of specific microorganisms solely driving cancer initiation and progression may need to be modified in certain circumstances. Although great advances have been made in understanding the complex interplay between the gastric microbiota and H. pylori in the development of gastric inflammation and cancer, detailed studies are still needed in well-defined human populations to compare differences in the microbiota of H. pylori-infected persons with and without neoplastic lesions. Cross-sectional studies can provide initial insights into microbial associations with cancer; however, reverse effects are a concern, as it is difficult to discern whether carcinogenesis leads to changes in the local microenvironment that creates a new niche for microbes or whether alterations in the microbial population or its functions contribute to carcinogenesis [33]. Due to the acidic nature of the stomach, most bacteria cannot survive in this environment. However, infection with H. pylori leads to achlorhydria of the stomach in a subset of colonized persons; thus, long-term H. pylori colonization and neutralization of the gastric environment may directly contribute to alterations in the gastric microbiota.
Since the gastric microbiota is more austere in terms of microbial breadth and depth compared to the intestinal microbiota, future studies should focus on assessing whether the composition of the gastric microbiome in different anatomical regions of the stomach exerts differential effects on cancer risk. This could be done through site-specific topographical mapping of the microbiota in the presence or absence of H. pylori as well as assessing differences in relation to different disease states along the gastric carcinogenesis cascade. Clearly, longitudinal studies that utilize sequential sampling to elucidate the temporal nature of microbial associations with premalignant lesions are needed. Details regarding patient populations, including age, gender, diet, and other comorbidities need to be assessed and compared in a rigorous fashion to discern whether any of these variables affect the potential for the gastric microbiome to influence disease. Since studies of the gastric microbiota have largely focused on bacterial communities, more in depth studies elucidating effects of other microorganisms that potentially populate the stomach in addition to bacteria, including fungi, protists, archaea, and viruses, are needed to fully characterize the gastric microbiome and its relationship with cancer risk. Furthermore, to more definitively determine cause versus effect, studies may also need to incorporate humanized mouse models to discern effects of the human gastric microbiome on disease. As we begin to understand and elucidate the specific role of the gastric microbiota and its effects on human health and disease, studies of these microbial populations in innovative systems will likely yield translational opportunities to reduce gastric cancer morbidity and mortality by improving screening, prevention, and treatment. It is tempting to speculate that future studies will identify specific combinatorial populations of bacteria that are predictive of pathologic outcomes, yielding strategies to manipulate the microbiota to ultimately prevent disease.
I thought they were separate. See here a paper that I just found randomly:
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006573
Drivers of susceptibility to gastric carcinogenesis include H. pylori strain-specific virulence determinants, host constituents, and environmental factors. Along with these elements, the microbiota of the stomach may also influence the development of gastric malignancies. The acidic environment of the stomach in conjunction with low levels of cultured bacteria from this site previously led to assumptions that the gastric niche was not able to support a diverse microbial community. However, recent advances in DNA sequencing of conserved ribosomal RNA genes, phylogenetic analyses, and computational methods have uncovered a complex microbiota within the human stomach with the potential for disease induction [2].
...
A first step in establishing causation is to take inventory of a particular resident microbial population, and several investigations have focused on defining microbial communities within the human stomach and the interactions of these populations with H. pylori (Fig 1A). Numerous groups have used PCR- and sequencing-based approaches to demonstrate that H. pylori-negative individuals harbor a highly diverse gastric microbiota dominated by 5 predominant phyla: Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria [13–15]. In contrast, among H. pylori-positive subjects, H. pylori is the single most abundant bacterium present in the stomach and accounts for between 72% and 97% of all sequence reads [13, 14].
...
Most bacteria cannot survive in the acidic environment of the stomach. However, it has been well established that, in a subset of persons, infection with H. pylori leads to achlorhydria and decreased acid secretion. Thus, long-term H. pylori colonization and neutralization of the gastric environment may directly contribute to alterations in the gastric microbiota. There are also clinical studies that support this concept, namely that patients treated with acid-suppressive drugs, such as proton pump inhibitors, exhibit a significant increase in the burden of non-H. pylori bacteria within the stomach. Of interest, this increase correlates with increased inflammatory responses, suggesting that non-H. pylori bacteria that colonize an achlorhydric stomach may have the capacity to promote inflammation that could potentially facilitate the progression to cancer [22, 23]. However, definitive evidence for this requires careful interventional studies that have yet to be performed.
...
In addition to the stomach, bacteria within other microbial niches may exert a role in modulating H. pylori-induced gastric inflammatory responses. Two studies have shown that precolonization with intestinal Helicobacters (H. bilis, H. hepaticus, and H. muridarum) can either increase or decrease the severity of gastric inflammation induced by H. pylori by altering T-regulatory cell responses [30, 31]. Another study demonstrated that H. pylori per se is present within the intestine in a coccoid form and that the interaction between phagocytes and H. pylori within intestinal Peyer’s patches plays a critical role in modifying the intensity of H. pylori-induced gastritis [32]. However, other studies have shown that the microflora within the stomach can accelerate the progression of gastric cancer in the presence of H. pylori and do so with no differences detected in the composition of the intestinal microbiota [27, 28]. Addressing whether the resident intestinal microbiome directly contributes to the pathophysiology of H. pylori-induced gastric diseases is an avenue that requires further investigation, and it is important to consider that the effects of bacteria and microbial communities in the intestine and the stomach on gastric pathophysiology may not be mutually exclusive.
...
Evidence that the host microbiota specifically functions to promote health and prevent disease and that dysbiosis contributes to inflammation, susceptibility to pathogens, and diseases (including cancer) is undisputed [3]. As a result, the concept of specific microorganisms solely driving cancer initiation and progression may need to be modified in certain circumstances. Although great advances have been made in understanding the complex interplay between the gastric microbiota and H. pylori in the development of gastric inflammation and cancer, detailed studies are still needed in well-defined human populations to compare differences in the microbiota of H. pylori-infected persons with and without neoplastic lesions. Cross-sectional studies can provide initial insights into microbial associations with cancer; however, reverse effects are a concern, as it is difficult to discern whether carcinogenesis leads to changes in the local microenvironment that creates a new niche for microbes or whether alterations in the microbial population or its functions contribute to carcinogenesis [33]. Due to the acidic nature of the stomach, most bacteria cannot survive in this environment. However, infection with H. pylori leads to achlorhydria of the stomach in a subset of colonized persons; thus, long-term H. pylori colonization and neutralization of the gastric environment may directly contribute to alterations in the gastric microbiota.
Since the gastric microbiota is more austere in terms of microbial breadth and depth compared to the intestinal microbiota, future studies should focus on assessing whether the composition of the gastric microbiome in different anatomical regions of the stomach exerts differential effects on cancer risk. This could be done through site-specific topographical mapping of the microbiota in the presence or absence of H. pylori as well as assessing differences in relation to different disease states along the gastric carcinogenesis cascade. Clearly, longitudinal studies that utilize sequential sampling to elucidate the temporal nature of microbial associations with premalignant lesions are needed. Details regarding patient populations, including age, gender, diet, and other comorbidities need to be assessed and compared in a rigorous fashion to discern whether any of these variables affect the potential for the gastric microbiome to influence disease. Since studies of the gastric microbiota have largely focused on bacterial communities, more in depth studies elucidating effects of other microorganisms that potentially populate the stomach in addition to bacteria, including fungi, protists, archaea, and viruses, are needed to fully characterize the gastric microbiome and its relationship with cancer risk. Furthermore, to more definitively determine cause versus effect, studies may also need to incorporate humanized mouse models to discern effects of the human gastric microbiome on disease. As we begin to understand and elucidate the specific role of the gastric microbiota and its effects on human health and disease, studies of these microbial populations in innovative systems will likely yield translational opportunities to reduce gastric cancer morbidity and mortality by improving screening, prevention, and treatment. It is tempting to speculate that future studies will identify specific combinatorial populations of bacteria that are predictive of pathologic outcomes, yielding strategies to manipulate the microbiota to ultimately prevent disease.
Michael Harrop
Active member
It is connected physically and via a wide range of mechanisms. https://humanmicrobiome.info/intro/#mechanisms
Also relevant: https://humanmicrobiome.info/oral/#does-the-oral-microbiome-colonize-the-gut
OP
GutBrainAxis
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- #87
Thanks.
I took a probiotic pill a couple days in a row. When I took the probiotic yesterday, it messed me up quite a bit. Is it normal for probiotics to make things worse at first? I can imagine that introducing new microbiota to your GI system could be disruptive.
I took a probiotic pill a couple days in a row. When I took the probiotic yesterday, it messed me up quite a bit. Is it normal for probiotics to make things worse at first? I can imagine that introducing new microbiota to your GI system could be disruptive.
Michael Harrop
Active member
I shared info on that numerous times in this thread. You don't seem to be processing the information you're given.
OP
GutBrainAxis
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1: Where was the info on disruption, sorry? My apologies about not reading information; my mental health is often really bad.
2: Was your previous point just that the gastric and intestinal microbiomes are connected? They're still talked about as distinct things in the literature, right?
3: H. pylori is a very famous (and rightly so) stomach thing. But there's not really any literature on gastric dysbiosis that doesn't involve H. pylori infection, correct? I remember reading once that gastric dysbiosis is a mysterious domain.
2: Was your previous point just that the gastric and intestinal microbiomes are connected? They're still talked about as distinct things in the literature, right?
3: H. pylori is a very famous (and rightly so) stomach thing. But there's not really any literature on gastric dysbiosis that doesn't involve H. pylori infection, correct? I remember reading once that gastric dysbiosis is a mysterious domain.
Michael Harrop
Active member
1. https://humanmicrobiome.info/probiotic-guide
2. Each part of the gut microbiome can have unique problems, but the whole thing is tightly interconnected.
3. I don't know.
2. Each part of the gut microbiome can have unique problems, but the whole thing is tightly interconnected.
3. I don't know.
OP
GutBrainAxis
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- #91
What do you make of this paper?
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.578386/full
Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host–microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host’s metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota–host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.
I also wonder what you make of this paper here:
https://www.nature.com/articles/s41570-023-00471-4
The human gut microbiome is a complex microbial community that is strongly linked to both host health and disease. However, the detailed molecular mechanisms underlying the effects of these microorganisms on host biology remain largely uncharacterized. The development of non-lethal, small-molecule inhibitors that target specific gut microbial activities enables a powerful but underutilized approach to studying the gut microbiome and a promising therapeutic strategy. In this Review, we will discuss the challenges of studying this microbial community, the historic use of small-molecule inhibitors in microbial ecology, and recent applications of this strategy. We also discuss the evidence suggesting that host-targeted drugs can affect the growth and metabolism of gut microbes. Finally, we address the issues of developing and implementing microbiome-targeted small-molecule inhibitors and define important future directions for this research.
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.578386/full
Hosting millions of microorganisms, the digestive tract is the primary and most important part of bacterial colonization. On one side, in cases of opportunistic invasion, the abundant bacterial population inside intestinal tissues may face potential health problems such as inflammation and infections. Therefore, the immune system has evolved to sustain the host–microbiota symbiotic relationship. On the other hand, to maintain host immune homeostasis, the intestinal microflora often exerts an immunoregulatory function that cannot be ignored. A field of great interest is the association of either microbiota or probiotics with the immune system concerning clinical uses. This microbial community regulates some of the host’s metabolic and physiological functions and drives early-life immune system maturation, contributing to their homeostasis throughout life. Changes in gut microbiota can occur through modification in function, composition (dysbiosis), or microbiota–host interplays. Studies on animals and humans show that probiotics can have a pivotal effect on the modulation of immune and inflammatory mechanisms; however, the precise mechanisms have not yet been well defined. Diet, age, BMI (body mass index), medications, and stress may confound the benefits of probiotic intake. In addition to host gut functions (permeability and physiology), all these agents have profound implications for the gut microbiome composition. The use of probiotics could improve the gut microbial population, increase mucus-secretion, and prevent the destruction of tight junction proteins by decreasing the number of lipopolysaccharides (LPSs). When LPS binds endothelial cells to toll-like receptors (TLR 2, 4), dendritic cells and macrophage cells are activated, and inflammatory markers are increased. Furthermore, a decrease in gut dysbiosis and intestinal leakage after probiotic therapy may minimize the development of inflammatory biomarkers and blunt unnecessary activation of the immune system. In turn, probiotics improve the differentiation of T-cells against Th2 and development of Th2 cytokines such as IL-4 and IL-10. The present narrative review explores the interactions between gut microflora/probiotics and the immune system starting from the general perspective of a biological plausibility to get to the in vitro and in vivo demonstrations of a probiotic-based approach up to the possible uses for novel therapeutic strategies.
I also wonder what you make of this paper here:
https://www.nature.com/articles/s41570-023-00471-4
The human gut microbiome is a complex microbial community that is strongly linked to both host health and disease. However, the detailed molecular mechanisms underlying the effects of these microorganisms on host biology remain largely uncharacterized. The development of non-lethal, small-molecule inhibitors that target specific gut microbial activities enables a powerful but underutilized approach to studying the gut microbiome and a promising therapeutic strategy. In this Review, we will discuss the challenges of studying this microbial community, the historic use of small-molecule inhibitors in microbial ecology, and recent applications of this strategy. We also discuss the evidence suggesting that host-targeted drugs can affect the growth and metabolism of gut microbes. Finally, we address the issues of developing and implementing microbiome-targeted small-molecule inhibitors and define important future directions for this research.
Michael Harrop
Active member
From a quick glance, they look like pretty standard papers. Why?
OP
GutBrainAxis
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I just wanted to know if you'd find anything interesting in those papers.
Have you tried pectin? What are your favorite prebiotics? I found this interesting:
https://www.sciencedirect.com/science/article/pii/S0268005X22004787
Have you tried pectin? What are your favorite prebiotics? I found this interesting:
https://www.sciencedirect.com/science/article/pii/S0268005X22004787
OP
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I apologize if I asked this previously, but why can't SCFAs just be supplemented directly? Why can't one just take pills that contain SCFAs? I know that that might not be as healthy as producing SCFAs the natural way in your colon, but nevertheless I wonder about whether direct supplementation of SCFAs might be informative; you could quickly find out whether you have a problem in the SCFA domain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005631/
The gut microbiota has attracted considerable attention in recent years, putting it in the spotlight of biomedical research. Recent studies have suggested that an intestinal bacteria imbalance plays a role in the development of several disorders. The bidirectional communication that occurs between the microbiota and its mammalian host can be mediated through a variety of mechanisms, and it is clear that the biochemical messengers produced by the microbiota are an important facet of this crosstalk. Convincing evidence exists that SCFAs produced by the intestinal microbiota are involved in gastrointestinal physiology, immune function, host metabolism, and even in development and homeostasis of the CNS.
Although our understanding of microbiota-host interactions has considerably increased over recent years, there is still an unmet requirement for a deeper understanding of the complex microbiota-gut-brain communication. Furthermore, since most studies have been conducted in rodents, one must be cautious when translating the effects of SCFAs on humans. Given that SCFAs can regulate CNS processes through direct and indirect means and ultimately shape behavior and cognitive function, a thorough comprehension of how these metabolites participate in these complex gut-brain interactions may aid in developing novel therapeutic targets for treating CNS disorders. Further, through their effects on the development and maintenance of healthy brain function, these metabolites hold the potential for use as dietary interventions with a range of psychological functions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005631/
The gut microbiota has attracted considerable attention in recent years, putting it in the spotlight of biomedical research. Recent studies have suggested that an intestinal bacteria imbalance plays a role in the development of several disorders. The bidirectional communication that occurs between the microbiota and its mammalian host can be mediated through a variety of mechanisms, and it is clear that the biochemical messengers produced by the microbiota are an important facet of this crosstalk. Convincing evidence exists that SCFAs produced by the intestinal microbiota are involved in gastrointestinal physiology, immune function, host metabolism, and even in development and homeostasis of the CNS.
Although our understanding of microbiota-host interactions has considerably increased over recent years, there is still an unmet requirement for a deeper understanding of the complex microbiota-gut-brain communication. Furthermore, since most studies have been conducted in rodents, one must be cautious when translating the effects of SCFAs on humans. Given that SCFAs can regulate CNS processes through direct and indirect means and ultimately shape behavior and cognitive function, a thorough comprehension of how these metabolites participate in these complex gut-brain interactions may aid in developing novel therapeutic targets for treating CNS disorders. Further, through their effects on the development and maintenance of healthy brain function, these metabolites hold the potential for use as dietary interventions with a range of psychological functions.
OP
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I just tried this today for the first time and so far it's been a smashing success: https://en.wikipedia.org/wiki/Quercetin.
I want to try bromelain too.
Do you know about bromelain and quercetin? Have you tried them yourself?
I want to try bromelain too.
Do you know about bromelain and quercetin? Have you tried them yourself?
OP
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Doesn't the below information provide some very clear ideas about what to try?
And yet doctors won't be able to recommend ideas to patients on the basis of the below information, right? Large-scale clinical trials are needed before doctors can recommend things, correct?
https://www.mdpi.com/1422-0067/25/1/38
Several research studies have shown that dysbiosis is a contributing factor to the development of neurological and psychiatric diseases. These include anxiety, depression, major depressive disorder (MDD), schizophrenia, bipolar disorder, autism, and obsessive-compulsive disorder (OCD) [117]. Acetate, lactate, butyrate, and propionate produced by anaerobic bacteria in the large intestine have a profound effect on reactions causing mental health issues. Experiments on animals have shown that butyrate inhibits histone deacetylase (HDAC) [56,118]. Overproduction of HDAC is associated with neurological disorders such as Parkinson’s disease, schizophrenia, and depression [118]. The inhibition of HDAC may thus be important in the treatment of brain trauma and dementia [118]. An increase in acetylated histones (ACHs), on the other hand, elevates the expression of the bdnf (brain-derived neurotrophic factor) gene in the frontal cortex and hippocampus and stimulates brain development [119,120]. Low levels of BDNF are associated with mood changes, depression, and anxiety [94,121,122,123]. Activation of G-protein-coupled receptors (GPCRs) by butyrate may lead to the development of multiple neurodegenerative disorders [56,118] and an increase in the production of inflammatory cytokines [124]. Butyrate (and other SCFAs) modifies the integrity of the blood–brain barrier (BBB) and the maturation of microglia [125,126]. In germ-free (GF) mice, the malfunctioning of microglia could be reversed by administering high levels of a combination of butyrate, propionate, and acetate [127]. The function of acetate is different in that it crosses the BBB and accumulates in the hypothalamus, where it controls appetite [79].
Oscillobacter spp. are known to produce valeric acid, a compound that closely resembles GABA and binds to GABA receptors [128]. With the binding of valeric acid to these receptors, GABA binding is inhibited, and the CNS signals are no longer blocked, resulting in anxiety. Of interest is that patients who suffer from anxiety and depression have lower Lactobacillus cell numbers. This is an important observation as certain Lactobacillus spp. stimulates the secretion of GABA as well as the neurotransmitter acetylcholine [129,130].
Hormone production regulated by gut microbiota interacts with EECs [131,132] and generates chemical signals that, in turn, react with the ENS. Bodily functions affected by changes in hormone levels include digestion, salivation, lacrimation, urination, defecation, and sexual arousal [133]. A clear association exists between chronic stress and gut inflammation disorders, such as IBD and IBS [115].
Inflammatory factors produced by Alistipes spp. could play a role in depression, anxiety, IBD, and chronic fatigue [134,135,136]. Prevotella spp. are often associated with pro-inflammatory responses characteristics, but low numbers of the species have also been associated with anxiety and depression [137]. Faecalibacterium prausnitzii (ATCC 27766) relieved anxiety and depression, suggesting that the strain may have psychobiotic properties [138]. This may have to do with increased levels of SCFA in the cecum, elevated plasma IL-10 levels, and lower levels of corticosterone and IL-6 [139]. Ruminococcus flavefaciens upregulated genes involved in mitochondrial oxidative phosphorylation whilst downregulating genes involved in synaptic signaling and neurogenesis [140]. Significantly lower levels of Proteobacteria, Haemophilus, Sutterella, and Clostridium spp. were reported in schizophrenic patients, whilst cell numbers of Anaerococcus spp. remained unchanged. Not all studies came to the same conclusion. In another study [141], high levels of Proteobacteria, Succinivibrio, Collinsella, Clostridium, and Klebsiella spp. but low levels of Blautia, Coprococcus, and Roseburia spp. were reported in schizophrenic patients [142,143]. Concluded from the study conducted by Qing et al. [144], Firmicutes live in synergy with actinobacteria, fusobacteria, and Acidobacteria, especially during the early stages of schizophrenia. High cell numbers of Firmicutes were reported to be present in the saliva of patients with primary Sjögren’s syndrome [145]. High levels of lactic acid bacteria, especially Lactobacillus gasseri, were reported in schizophrenic patients. Bacteriodetes and Acinetobacteria, on the other hand, were in the minority [146]. In contrast to previous studies, the presence of Proteobacteria did not differ significantly between schizophrenic and non-schizophrenic patients.
Anaerococcus and Collinsella isolated from schizophrenic individuals are known to produce high levels of butyrate [142,143]. In bipolar and autistic patients, butyrate-producing Faecalibacterium spp. was present in low numbers [147]. Patients with bipolar disorder are often diagnosed with an increase in gut wall permeability [148] and an increase in Flavonifractor [149]. Species in this genus cleave the flavonoid quercetin [149]. The latter has antioxidative and anti-inflammatory properties [150], and changes in its levels could lead to bipolar disorder. Other changes in bacterial populations included a decrease in Faecalibacterium and an increase in Actinobacteria and Coriobacteriaceae [151]. Evans et al. [152] reported a decrease in Faecalibacterium and Ruminococcaceae in bipolar patients. The decrease in Faecalibacterium resulted in a decline in anti-inflammatory reactions [153].
An increase in Clostridium spp. was reported in patients diagnosed with autism [154]. In a more detailed study on the complete microbiome of autistic patients, Finegold et al. [155] reported a significant increase in Bacteroidetes, Acintobacterium, and Proteobacterium spp. but a decline in Firmicutes in autistic patients. High cell numbers of Clostridium defense, Clostridium hathewayi, and Clostridium orbiscindens were isolated from autistic patients. Faecalibacterium and Ruminococcus spp. were less abundant, which is an important observation given the anti-inflammatory properties of these species.
Obsessive-compulsive disorder (OCD), diagnosed in 2.3% of the population (mostly men), with a predominance in men [156], was originally classified as an anxiety disorder, similar to autism. Little is known about the gut microbial composition of individuals with OCD. Turna et al. [157] reported low numbers of Oscillospira, Odoribacter, and Anaerostipes spp. in OCD patients. Odoribacter produces butyrate, and low cell numbers may lead to an increase in inflammation, which may be the onset of OCD [158]. Experiments on mice showed a decrease in OCD when treated with Lactobacillus rhamnosus. In humans, similar findings were reported with the administration of Lactobacillus helveticus [159,160]. Findings such as these may provide valuable information in future research aimed at developing psychobiotics. For more information on probiotics and the effect on the nervous system, the reader is referred to the review published by Cryan et al. [161].
The production of trace amines β-phenylethylamine (PEA), p-tyramine (TYR), and tryptamine (TRP) by commensal gut microbiota is well-documented [162,163,164] as many gut bacteria can produce aromatic L-amino acid decarboxylase (AADC; EC 4.1.1.28) [165]. Unlike DOPA, NE, EPI, and 5-HT, PEA, TYR, and TRP are not stored and rapidly diffuse across membranes [166,167]. PEA diffuses across the blood–brain barrier and TYR passes through IECs [168]. Tyrosine is converted to l-3,4-dihydroxyphenylalanine (l-DOPA), the precursor of DOPA, NE, and EPI [168]. A deficiency in L-tyrosine may thus lead to anxiety and low mood [168]. Treatments that increase monoamine neurotransmitter receptor activation lead to a decrease in PEA and TYR synthesis. Likewise, treatments that decrease receptor activation result in an increase in PEA and TYR synthesis. Reports on changes in AADC activity are almost exclusively based on L-DOPA as a substrate. Binding of PEA, TYR, TRP, and OCT to the trace-amine-associated receptor TAAR1 in the brain regulates the release of neurotransmitters dopamine and serotonin [169]. Under- or overexpression of TAAR1 may lead to schizophrenia, depression, and addiction [170].
The gut microbiota has a vast effect on our mental health. Chemicals secreted by these bacteria, such as GABA, in addition to other metabolites, play an important role in anti-inflammatory responses and help to alleviate psychiatric symptoms stemming from inflammation. Treatment of schizophrenic and bipolar patients with probiotics alleviated symptoms associated with IBD, autistic children benefitted from probiotic treatment, and OCD-like behavior could be controlled (reviewed by Dicks et al.) [117]. The same review addresses the role that specific gut microbiota play in mental health and lists the species responsible for each mental condition.
And yet doctors won't be able to recommend ideas to patients on the basis of the below information, right? Large-scale clinical trials are needed before doctors can recommend things, correct?
https://www.mdpi.com/1422-0067/25/1/38
Several research studies have shown that dysbiosis is a contributing factor to the development of neurological and psychiatric diseases. These include anxiety, depression, major depressive disorder (MDD), schizophrenia, bipolar disorder, autism, and obsessive-compulsive disorder (OCD) [117]. Acetate, lactate, butyrate, and propionate produced by anaerobic bacteria in the large intestine have a profound effect on reactions causing mental health issues. Experiments on animals have shown that butyrate inhibits histone deacetylase (HDAC) [56,118]. Overproduction of HDAC is associated with neurological disorders such as Parkinson’s disease, schizophrenia, and depression [118]. The inhibition of HDAC may thus be important in the treatment of brain trauma and dementia [118]. An increase in acetylated histones (ACHs), on the other hand, elevates the expression of the bdnf (brain-derived neurotrophic factor) gene in the frontal cortex and hippocampus and stimulates brain development [119,120]. Low levels of BDNF are associated with mood changes, depression, and anxiety [94,121,122,123]. Activation of G-protein-coupled receptors (GPCRs) by butyrate may lead to the development of multiple neurodegenerative disorders [56,118] and an increase in the production of inflammatory cytokines [124]. Butyrate (and other SCFAs) modifies the integrity of the blood–brain barrier (BBB) and the maturation of microglia [125,126]. In germ-free (GF) mice, the malfunctioning of microglia could be reversed by administering high levels of a combination of butyrate, propionate, and acetate [127]. The function of acetate is different in that it crosses the BBB and accumulates in the hypothalamus, where it controls appetite [79].
Oscillobacter spp. are known to produce valeric acid, a compound that closely resembles GABA and binds to GABA receptors [128]. With the binding of valeric acid to these receptors, GABA binding is inhibited, and the CNS signals are no longer blocked, resulting in anxiety. Of interest is that patients who suffer from anxiety and depression have lower Lactobacillus cell numbers. This is an important observation as certain Lactobacillus spp. stimulates the secretion of GABA as well as the neurotransmitter acetylcholine [129,130].
Hormone production regulated by gut microbiota interacts with EECs [131,132] and generates chemical signals that, in turn, react with the ENS. Bodily functions affected by changes in hormone levels include digestion, salivation, lacrimation, urination, defecation, and sexual arousal [133]. A clear association exists between chronic stress and gut inflammation disorders, such as IBD and IBS [115].
Inflammatory factors produced by Alistipes spp. could play a role in depression, anxiety, IBD, and chronic fatigue [134,135,136]. Prevotella spp. are often associated with pro-inflammatory responses characteristics, but low numbers of the species have also been associated with anxiety and depression [137]. Faecalibacterium prausnitzii (ATCC 27766) relieved anxiety and depression, suggesting that the strain may have psychobiotic properties [138]. This may have to do with increased levels of SCFA in the cecum, elevated plasma IL-10 levels, and lower levels of corticosterone and IL-6 [139]. Ruminococcus flavefaciens upregulated genes involved in mitochondrial oxidative phosphorylation whilst downregulating genes involved in synaptic signaling and neurogenesis [140]. Significantly lower levels of Proteobacteria, Haemophilus, Sutterella, and Clostridium spp. were reported in schizophrenic patients, whilst cell numbers of Anaerococcus spp. remained unchanged. Not all studies came to the same conclusion. In another study [141], high levels of Proteobacteria, Succinivibrio, Collinsella, Clostridium, and Klebsiella spp. but low levels of Blautia, Coprococcus, and Roseburia spp. were reported in schizophrenic patients [142,143]. Concluded from the study conducted by Qing et al. [144], Firmicutes live in synergy with actinobacteria, fusobacteria, and Acidobacteria, especially during the early stages of schizophrenia. High cell numbers of Firmicutes were reported to be present in the saliva of patients with primary Sjögren’s syndrome [145]. High levels of lactic acid bacteria, especially Lactobacillus gasseri, were reported in schizophrenic patients. Bacteriodetes and Acinetobacteria, on the other hand, were in the minority [146]. In contrast to previous studies, the presence of Proteobacteria did not differ significantly between schizophrenic and non-schizophrenic patients.
Anaerococcus and Collinsella isolated from schizophrenic individuals are known to produce high levels of butyrate [142,143]. In bipolar and autistic patients, butyrate-producing Faecalibacterium spp. was present in low numbers [147]. Patients with bipolar disorder are often diagnosed with an increase in gut wall permeability [148] and an increase in Flavonifractor [149]. Species in this genus cleave the flavonoid quercetin [149]. The latter has antioxidative and anti-inflammatory properties [150], and changes in its levels could lead to bipolar disorder. Other changes in bacterial populations included a decrease in Faecalibacterium and an increase in Actinobacteria and Coriobacteriaceae [151]. Evans et al. [152] reported a decrease in Faecalibacterium and Ruminococcaceae in bipolar patients. The decrease in Faecalibacterium resulted in a decline in anti-inflammatory reactions [153].
An increase in Clostridium spp. was reported in patients diagnosed with autism [154]. In a more detailed study on the complete microbiome of autistic patients, Finegold et al. [155] reported a significant increase in Bacteroidetes, Acintobacterium, and Proteobacterium spp. but a decline in Firmicutes in autistic patients. High cell numbers of Clostridium defense, Clostridium hathewayi, and Clostridium orbiscindens were isolated from autistic patients. Faecalibacterium and Ruminococcus spp. were less abundant, which is an important observation given the anti-inflammatory properties of these species.
Obsessive-compulsive disorder (OCD), diagnosed in 2.3% of the population (mostly men), with a predominance in men [156], was originally classified as an anxiety disorder, similar to autism. Little is known about the gut microbial composition of individuals with OCD. Turna et al. [157] reported low numbers of Oscillospira, Odoribacter, and Anaerostipes spp. in OCD patients. Odoribacter produces butyrate, and low cell numbers may lead to an increase in inflammation, which may be the onset of OCD [158]. Experiments on mice showed a decrease in OCD when treated with Lactobacillus rhamnosus. In humans, similar findings were reported with the administration of Lactobacillus helveticus [159,160]. Findings such as these may provide valuable information in future research aimed at developing psychobiotics. For more information on probiotics and the effect on the nervous system, the reader is referred to the review published by Cryan et al. [161].
The production of trace amines β-phenylethylamine (PEA), p-tyramine (TYR), and tryptamine (TRP) by commensal gut microbiota is well-documented [162,163,164] as many gut bacteria can produce aromatic L-amino acid decarboxylase (AADC; EC 4.1.1.28) [165]. Unlike DOPA, NE, EPI, and 5-HT, PEA, TYR, and TRP are not stored and rapidly diffuse across membranes [166,167]. PEA diffuses across the blood–brain barrier and TYR passes through IECs [168]. Tyrosine is converted to l-3,4-dihydroxyphenylalanine (l-DOPA), the precursor of DOPA, NE, and EPI [168]. A deficiency in L-tyrosine may thus lead to anxiety and low mood [168]. Treatments that increase monoamine neurotransmitter receptor activation lead to a decrease in PEA and TYR synthesis. Likewise, treatments that decrease receptor activation result in an increase in PEA and TYR synthesis. Reports on changes in AADC activity are almost exclusively based on L-DOPA as a substrate. Binding of PEA, TYR, TRP, and OCT to the trace-amine-associated receptor TAAR1 in the brain regulates the release of neurotransmitters dopamine and serotonin [169]. Under- or overexpression of TAAR1 may lead to schizophrenia, depression, and addiction [170].
The gut microbiota has a vast effect on our mental health. Chemicals secreted by these bacteria, such as GABA, in addition to other metabolites, play an important role in anti-inflammatory responses and help to alleviate psychiatric symptoms stemming from inflammation. Treatment of schizophrenic and bipolar patients with probiotics alleviated symptoms associated with IBD, autistic children benefitted from probiotic treatment, and OCD-like behavior could be controlled (reviewed by Dicks et al.) [117]. The same review addresses the role that specific gut microbiota play in mental health and lists the species responsible for each mental condition.
Michael Harrop
Active member
I eat lots of fruit.
I think GOS is the only one that has been significantly helpful for me at any point. But it's not anymore. https://humanmicrobiome.info/probiotic-guide/#recommendations
Yes, I think you did.
I started taking Quercetin many years ago when I was close to death and it seemed like intestinal permeability was the main issue. I saw research that said quercetin was good for that. I tried it along with other similar supplements that had some evidence to help with permeability. None of them helped. FMT is what saved me. I've tried virtually everything over the past two decades and I'm convinced that FMT is the only intervention worth focusing on.
Correct.
Using quotes is better than bolding. I find large chunks of bolded text to be hard to read.
OP
GutBrainAxis
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- #98
1: Just to reiterate something we talked about previously, we can't possibly know how much impact on the human brain and body the loss of various bacterial strains has had, correct?
2: What is the "ceiling" in terms of the maximum impact that the loss of a single strain could have on the human brain and body?
3: I will try all of your recommendations; thanks for those. This looks neat:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296087/
4: Why (in your own case) do you think that some treatments have worked well but then faded?
5: What do you imagine is actually wrong with your gut biota? I haven't ever in my life heard of such a severe case of dysbiosis as what you describe; not sure how that came about.
I've been doing amazingly well (so far) with quercetin. Just a couple questions; not sure if you know about this stuff.
1: I have a form of quercetin that has "40 TIMES GREATER ABSORPTION THAN QUERCETIN". But why does quercetin even need to absorb in order to take action within the GI system? I think that some substances are referred to as "locally acting", which means that no absorption is necessary, since the substances just move through the GI tract and take action within the GI tract.
2: Regarding the below, is there any danger at all that sending quercetin into the gut will "feed" Flavonifractor and lead to undesirable proliferation of Flavonifractor? The below says that the "bacterial genus responsible for the breakdown of quercetin"; not sure if that means that quercetin is actually its food or not.
https://www.mdpi.com/1422-0067/22/7/3723
2: What is the "ceiling" in terms of the maximum impact that the loss of a single strain could have on the human brain and body?
3: I will try all of your recommendations; thanks for those. This looks neat:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296087/
4: Why (in your own case) do you think that some treatments have worked well but then faded?
5: What do you imagine is actually wrong with your gut biota? I haven't ever in my life heard of such a severe case of dysbiosis as what you describe; not sure how that came about.
I've been doing amazingly well (so far) with quercetin. Just a couple questions; not sure if you know about this stuff.
1: I have a form of quercetin that has "40 TIMES GREATER ABSORPTION THAN QUERCETIN". But why does quercetin even need to absorb in order to take action within the GI system? I think that some substances are referred to as "locally acting", which means that no absorption is necessary, since the substances just move through the GI tract and take action within the GI tract.
2: Regarding the below, is there any danger at all that sending quercetin into the gut will "feed" Flavonifractor and lead to undesirable proliferation of Flavonifractor? The below says that the "bacterial genus responsible for the breakdown of quercetin"; not sure if that means that quercetin is actually its food or not.
https://www.mdpi.com/1422-0067/22/7/3723
OP
GutBrainAxis
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- #99
Have you tried this and is it worth trying? https://seed.com/daily-synbiotic
1: Have you tried a VERY high dose of bromelain? And of quercetin? And of both of the two?
2: Why did the below work so well for you but then stop working? I don't get it. Have you asked scientists why something might work so well and then stop working? How long did it work for?
https://jarrow.com/products/saccharomyces-boulardii-mos-5-billion-cfu-delayed-release-veggie-caps
The yeast that you recommended has been life-changing for me. Thank you SO much for telling me about that; it truly has changed my life and I might not have found it for a long time without your recommendation. I used this one here: https://aor.ca/product/saccharomyces-boulardii/.
I guess the other heavy-hitter for me has been this (VERY high doses of it): https://nowfoods.ca/product/bromelain-500-mg-2400-gdu-g/.
Do you know any other major weapons against gut inflammation that I can try? For me it's all about combatting gut inflammation; anything that's renowned for doing that and has really good science behind it (science that shows that it combats inflammation really effectively) will probably be a huge deal for me. Let me know.
I wonder if some people don't take enough of the yeast? Or don't take enough of the bromelain?
How well do probiotics displace the resident microbiota? Do you know any good literature on that topic?
Someone suggested to me that maybe the biota that are best able to colonize one's gut (given the current diet) are already present in one's gut. Is that incorrect?
Apparently this study shows that the effect on the composition of the microbiome is basically negligible: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303609/
Have you tried this? https://aor.ca/product/probiotic-3/
Do you think that it's a good product? It contains three probiotics that apparently have some kind of synergy together and that apparently are popular in Asia but not in North America.
1: Have you tried a VERY high dose of bromelain? And of quercetin? And of both of the two?
2: Why did the below work so well for you but then stop working? I don't get it. Have you asked scientists why something might work so well and then stop working? How long did it work for?
https://jarrow.com/products/saccharomyces-boulardii-mos-5-billion-cfu-delayed-release-veggie-caps
The yeast that you recommended has been life-changing for me. Thank you SO much for telling me about that; it truly has changed my life and I might not have found it for a long time without your recommendation. I used this one here: https://aor.ca/product/saccharomyces-boulardii/.
I guess the other heavy-hitter for me has been this (VERY high doses of it): https://nowfoods.ca/product/bromelain-500-mg-2400-gdu-g/.
Do you know any other major weapons against gut inflammation that I can try? For me it's all about combatting gut inflammation; anything that's renowned for doing that and has really good science behind it (science that shows that it combats inflammation really effectively) will probably be a huge deal for me. Let me know.
I wonder if some people don't take enough of the yeast? Or don't take enough of the bromelain?
How well do probiotics displace the resident microbiota? Do you know any good literature on that topic?
Someone suggested to me that maybe the biota that are best able to colonize one's gut (given the current diet) are already present in one's gut. Is that incorrect?
Apparently this study shows that the effect on the composition of the microbiome is basically negligible: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3303609/
Have you tried this? https://aor.ca/product/probiotic-3/
Do you think that it's a good product? It contains three probiotics that apparently have some kind of synergy together and that apparently are popular in Asia but not in North America.
Michael Harrop
Active member
You can study and learn the impacts of the gut microbiome on the whole body. You can do FMT studies in animals to see what happens when you damage or restore the gut microbiome. You can compare modern urban populations to rural ones like the Hadza.
This has all been done, and you can read Martin Blaser's book "Missing Microbes" that covers it.
Covered below.
"Gut dysbiosis". There are plenty (millions) of people as bad or worse than me. They just haven't identified their problems as stemming from gut dysbiosis.
There is always the possibility that any "prebiotic" or "beneficial" compound will have detrimental impacts on some individuals.
Essentially, yes.
All I know is they heavily market their product. There is a lot of "activity", good and bad, about them on social media. But it's hard to know what's real and what's astroturfing.
No.
As noted in the probiotic guide, I took a soil-based probiotic that completely changed my gut microbiome (in a detrimental way). And then did FMT from donors which also caused major changes.
Their impacts are generally temporary, for as long as you keep taking them. https://humanmicrobiome.info/probiotics/
There are some reports in FMT studies that the strains most likely to colonize are similar to the ones in the recipient's gut. I don't recall the exact study. You can check the FMT wiki page.
I don't recall if I tried it. It looks like it may be worth trying.