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
- 42
- 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
- 42
- 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
- 42
- 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
New member
- Joined
- Jan 22, 2024
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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.