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?

1: If there's a microbe that "eats" quercetin and you pump quercetin in your body, that's a great thing. But do you know any actual papers on the notion that pumping nutrients into your gut will end up expanding the population of whichever microbes eat that nutrient? Maybe there aren't any papers on this topic, but I'd be curious to see any that exist. Every nutrient, you'd think, would have a liability attached to it in this regard. Including quercetin and everything else.

2: You seem like the type of person who's not shy about trying high doses of bromelain or S. boulardii or whatever else. Is my impression correct? I myself am not shy about trying high doses or quercetin, bromelain, S. boulardii, and so on. I often wonder to myself whether others out there were so close to having a breakthrough but they just didn't increase the dose enough regarding a given product.

3: I have this product ( https://aor.ca/product/probiotic-3/ ) in my fridge but I don't want to try it because right now I'm taking S. boulardii and Align. If I add a third product, it'll "muddy the waters", correct?

4: Is it OK to put probiotics in your fridge before (!!!) you open them?

5: I don't really get the whole dynamic regarding probiotics. I'm currently sending two probiotic products (S. boulardii and Align) into my gut daily. Why are neither of those "taking root"? Why are neither of those things able to either displace other biota or occupy uncolonized space?

6: It's expensive if you have to take a probiotic product forever because it never "takes root" in your gut, correct?
 
GutBrainAxis said:
do you know any actual papers on the notion that
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You can check the "diet" section of the wiki. It probably covers that.

2. True, anything is possible. I haven't tried it.

3. You'd have to try and see.

4. ??

5. Covered in the probiotic guide and probiotics wiki page.

6. Indeed, cost is a factor for #2 as well.
 
1: My curiosity about "muddying the waters" was that if you resist the temptation to add another probiotic to the ones you''re taking then you'll get better information than if you rush ahead. Do you see the conundrum? Adding new probiotics might improve things but also "muddies the waters" in terms of getting clear information about how things are impacting you.

2: Is it harmless to put a probiotic in the fridge before opening it? I thought that maybe you were only supposed to put them in the fridge after opening them; maybe a dumb question, so I apologize.

3: Did you try the below one?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10301191/
The scientific interest on Akkermansia muciniphila arises from evidence highlighting that its abundance in the gut correlates with host health, while its alterations with several dysfunctions [9,10,11]. This is the case of metabolic diseases including obesity, type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD) and non-alcoholic fatty liver disease (NAFLD), in which the levels of Akkermansia muciniphila decrease. However, at the same time, an excessive enrichment in Akkermansia muciniphila, in specific intestinal microenvironments, may exacerbate local inflammation caused by damages on the epithelial barrier [12,13,14]. For instance, increasing Akkermansia in a condition of Salmonella typhimurium infection or in a condition of intestinal bowel diseases could have no expected beneficial effects [14,15].
In addition, a cautionary note on its wide use has come from the neurologic field since in some pathological contexts, including Parkinson’s disease (PD) and multiple sclerosis (MS), the intestinal microbiota exhibits a characteristic signature of Akkermansia municiphila abundance [16].
Therefore, in light of these controversial points, evaluating the use of Akkermansia on an individual basis should be critically considered.
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I wonder if the microbes in my probiotics only reside in my gut for a brief duration. That's possible, correct? Maybe you have to take more of a probiotic very soon in order to maintain the beneficial effects.
 
GutBrainAxis said:
I wonder if the microbes in my probiotics only reside in my gut for a brief duration. That's possible, correct? Maybe you have to take more of a probiotic very soon in order to maintain the beneficial effects.
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Even my gastroenterologist who performed my most successful FMT (back when I had C. diff) said this much. We get certain bacteria from our parents and other people we are around as babies, either directly through the birth process and/or close contact, or indirectly through the shared home environment. These are the strains that colonize us for life.

Also, the currently available probiotics encompass a VERY small fraction of the bacterial world. Over 90% of probiotic strains are from one small group of bacteria, the lactic acid bacteria, that convert sugars to lactic acid. The reason these became probiotics was because they had already been used by humans to ferment and preserve food for centuries. In other words, the path wasn't "Here are bacteria that are missing in people given antibiotics, let's culture and take those", it was much more like, "We already eat these bacteria in food, let's try to find all the good things they do for us". Essentially, these bacteria are regarded as "beneficial" because those are the ones we studied for their beneficial effects.

Probably the best thing that can be said about them is A), they are safe in the don't-put-you-in-the-hospital sense (unless you have some physically--not just microbially dysbiotic, and not just "leaky" to things like allergens, but actually failing outright to keep the inside and outside separated--gut, and likely immunosuppression on top of it, in those cases serious blood infections even with LAB are occasionally a thing), and B) they crowd out certain bad bacteria you might ingest by just being there and creating lactic acid. But they don't really grow on anything other than sugars, they have "gaps" (missing enzymes) in major metabolic pathways like respiration, and are just generally low diversity. The probiotic companies love to claim that their "pet" strain is worlds better than all the others, but it doesn't change the fact that they are all essentially cousins.

There are a FEW other bacteria represented--like various Bacillus species, a few Clostridia (found in Pendulum brand probiotics only), Akkermansia muciniphila (again Pendulum only) a few strains of E. coli (Nissle, Symbioflor) you need to order from Europe to get, most recently a strain of Propionibacterium (the bacteria that make holes in Swiss cheese) and the soil-based bacteria Michael mentioned (the Bacillus species are soil bacteria too--however there are many OTHER soil-dwelling organisms found in a true "soil based" probiotic like Prescript-Assist). And there are yeast, you mention Saccharomyces boulardii, which is really just a special strain of ordinary baker's/brewer's yeast, S. cervisiae. While somewhat more diverse, again there's the caveat that (with the possible exception of Akkermansia), there's no reason to believe that these are major keystone species lost from the gut when you take antibiotics and whose absence is the cause of the "missing microbes" phenomenon.

The situation with FMT is you get a community of bacteria that already form a functioning gut. Even if their species are known bacteria that are somewhat studied, it's likely they have adapted to the donor's gut in ways that even a strain of the same species that you get off of an unwashed plant leaf or from the soil hasn't.
 
I posted the below:

What is the best and latest science on how long a given probiotic will (for better or for worse) remain in your system?

I get the sense that people will take a probiotic on a daily basis for a long period of time (or even forever). Doing that is expensive. But if a probiotic won't remain in your system then you have no choice but to keep taking it, I guess.

I have a probiotic that I took for a week or so and that I'm unsure about; it might turn out to be a "winner" for me or it might turn out to be useless or even harmful. It's mildly worrying that a harmful probiotic will remain in your system for a long time; how do you "dislodge" it if you want to remove it from your system?

1: A given probiotic microbe is supposed to reside in a certain GI-tract location like the colon (or some specific part of the colon), so what ensures that a given probiotic microbe (that's been ingested) will get to and then stay at the appropriate location in the GI tract? What if the microbe travels too far or not far enough?

2: Does the body "get used to" a probiotic microbe such that the body's reaction to the microbe changes a lot over time? By what mechanisms does this "adaptation" occur? Regarding the ingestion of probiotic microbes, it would be great if one could expect to see better and better and faster and faster results over time.

I've been taking an Align product and a Culturelle product. You know how those brands each have a major probiotic bacteria? In fact, I don't even know if each of those brands sells anything other than their one probiotic bacteria.

I've also been talking S. boulardii.

Regarding the three probiotic microbes that I referred to above, it seems like I took them for a week or so and then stopped. And it seems like the benefits showed up some time after I stopped taking them; it's like they "took hold" in my GI tract and then the benefits showed up later on. What do you make of that?

I just felt really tired when I was taking them so I got the sense that my body was getting overwhelmed. I stopped taking them, and then the benefits showed up later.
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I got this response so far:

Probiotics almost never truly colonize the gut - with some exceptions (see below). Most probiotics act transiently, if they act at all, and then pass on. It’s very difficult to manipulate the gut microbiome in adults to a meaningful degree, especially with bacteria that aren’t dominant components of the adult gut microbiome.

Probiotics aren’t harmful by definition - to be a probiotic, it needs to provide a benefit to the host. (See here: https://pubmed.ncbi.nlm.nih.gov/24912386/)

There is evidence you can get some probiotic strains to colonize (establish long term), but only in selected cases with specific organisms:

  1. There’s one study I’m familiar with in adults, but only in people with “vacancy” in their gut microbiome: https://pubmed.ncbi.nlm.nih.gov/27693307/
  2. Infants can be durably colonized by some infant associated bifidobacteria, if that organism is something like B. infantis: https://pubmed.ncbi.nlm.nih.gov/29242832/ and https://pubmed.ncbi.nlm.nih.gov/33762689/
And yes, it’s very good for the infant: https://pubmed.ncbi.nlm.nih.gov/34143954/

Source: I’m a PhD microbial ecologist who studies host-microbe interactions in humans.
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I wonder what limitations the studies linked above (by the PhD guy) have.

And to what extent can those studies' conclusions really be generalized? People are different, right?

I really hope that I can change my gut-biota situation. Otherwise I'm in a bit of trouble.

The FMT option is obviously way way way less convenient than just taking pills that contain probiotics.

SFBayFMT5 said:
Even my gastroenterologist who performed my most successful FMT (back when I had C. diff) said this much. We get certain bacteria from our parents and other people we are around as babies, either directly through the birth process and/or close contact, or indirectly through the shared home environment. These are the strains that colonize us for life.

Also, the currently available probiotics encompass a VERY small fraction of the bacterial world. Over 90% of probiotic strains are from one small group of bacteria, the lactic acid bacteria, that convert sugars to lactic acid. The reason these became probiotics was because they had already been used by humans to ferment and preserve food for centuries. In other words, the path wasn't "Here are bacteria that are missing in people given antibiotics, let's culture and take those", it was much more like, "We already eat these bacteria in food, let's try to find all the good things they do for us". Essentially, these bacteria are regarded as "beneficial" because those are the ones we studied for their beneficial effects.

Probably the best thing that can be said about them is A), they are safe in the don't-put-you-in-the-hospital sense (unless you have some physically--not just microbially dysbiotic, and not just "leaky" to things like allergens, but actually failing outright to keep the inside and outside separated--gut, and likely immunosuppression on top of it, in those cases serious blood infections even with LAB are occasionally a thing), and B) they crowd out certain bad bacteria you might ingest by just being there and creating lactic acid. But they don't really grow on anything other than sugars, they have "gaps" (missing enzymes) in major metabolic pathways like respiration, and are just generally low diversity. The probiotic companies love to claim that their "pet" strain is worlds better than all the others, but it doesn't change the fact that they are all essentially cousins.

There are a FEW other bacteria represented--like various Bacillus species, a few Clostridia (found in Pendulum brand probiotics only), Akkermansia muciniphila (again Pendulum only) a few strains of E. coli (Nissle, Symbioflor) you need to order from Europe to get, most recently a strain of Propionibacterium (the bacteria that make holes in Swiss cheese) and the soil-based bacteria Michael mentioned (the Bacillus species are soil bacteria too--however there are many OTHER soil-dwelling organisms found in a true "soil based" probiotic like Prescript-Assist). And there are yeast, you mention Saccharomyces boulardii, which is really just a special strain of ordinary baker's/brewer's yeast, S. cervisiae. While somewhat more diverse, again there's the caveat that (with the possible exception of Akkermansia), there's no reason to believe that these are major keystone species lost from the gut when you take antibiotics and whose absence is the cause of the "missing microbes" phenomenon.

The situation with FMT is you get a community of bacteria that already form a functioning gut. Even if their species are known bacteria that are somewhat studied, it's likely they have adapted to the donor's gut in ways that even a strain of the same species that you get off of an unwashed plant leaf or from the soil hasn't.
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Thanks for this excellent comment; I will definitely explore all of these topics.

I want to try all of the probiotics that you mention here.

What are your favorite probiotics, by the way? I know that people are different, but I wonder which probiotics have been "winners" for you personally.

I heard that probiotics don't "take hold" in one's body in the way that one might wish. But I'm happy to take probiotics on a daily basis forever if necessary.

I'm even willing to do FMT, but I have no idea where I'll get the money for that. I'm not sure what the whole process is that you have to go through in order to get FMT.
 
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I wonder about this:
https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.993451/full
The use of Bacillus licheniformis as a probiotic has increased significantly in recent years. Published reports demonstrate that it provides multiple benefits for health. Although there are already studies in humans and is marketed, it is mostly used in the veterinary industry still. However, its benefits could be extrapolated to humans in future. This review addresses the application of B. licheniformis, its sporulation, mechanisms of action, and its role in the resolution, treatment, and prevention of different conditions and diseases. It focuses on scientific advances from 2016 to mid-2022 and emphasizes the most common diseases in the general population. Most of the 70% of published studies about the health benefits of B. licheniformis have been published from 2016 until now. The intake of B. licheniformis has been related to the effects of modulation of the intestinal microbiota, antimicrobial activity, growth promotion, anti-inflammatory and immunostimulatory effects, promotion of the regulation of the lipid profile, increase of neurotransmitters, and stress reduction, among others. These results provide novel possible applications of this and other probiotics in general. Although many benefits can be reported on a microorganism, the combination with others could provide a better effect. Further studies like this need to be done to understand the specific advantages of each probiotic and its strains and therefore achieve a better selection of them for a specific disease or disorder.
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Some probiotics are mentioned below that I haven't heard much about. I'd love to try some of these less-known probiotics eventually if the better-known ones aren't sufficient.

https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1118529/full

In contrast, both experimental and clinical studies revealed that probiotics based on Bacillus licheniformis, Saccharomyces boulardii, Lactobacillus rhamnosus, and Bifidobacterium spp. contributed to the inhibition of stress-induced HPA axis hyperactivity, as well as alleviated depressive-like behavior and anxiety-related behavior (Eutamene et al., 2007; Gareau et al., 2007; Desbonnet et al., 2010).
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...

However, the results of studies on the effect of probiotics on symptom improvement in patients with AD are inconclusive. Akbari et al. (2016) showed that after 12 weeks of daily administration of a mixture of Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum, AD patients showed a significant improvement in mini-mental state exam results. On the other hand, the administration of two different probiotic mixtures: one containing Lactobacillus fermentum, Lactobacillus plantarum, and Bifidobacterium lactis and the other containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum, did not contribute to the improvement of cognitive functions in patients with severe Alzheimer’s disease (Agahi et al., 2018). Moreover, numerous studies indicate a well-chosen diet as a quick way to modify the composition and metabolism of the gut microbiota, reduce inflammation, and help maintain eubiosis and proper dependencies in the gut-brain axis (Metta et al., 2022; Varesi et al., 2022).
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Pepto Bismol has a huge effect on me. My endoscopy apparently indicated that I don't have an H. pylori infection, but there's some uncertainty; the report itself says that the test is not perfect.

Suppose I don't have H. pylori. How is the Pepto Bismol impacting me? What's the mechanism? Is there some other microbe (not H. pylori) that the Pepto Bismol is killing? Or...? Big mystery.

What do you guys think about the strains included in this product? https://www.nowfoods.com/products/supplements/probiotic-10-25-billion-veg-capsules
 
GutBrainAxis said:
I wonder what limitations the studies linked above (by the PhD guy) have.

And to what extent can those studies' conclusions really be generalized? People are different, right?
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As the probiotics, diet, and prebiotics pages all indicate, things vary quite a bit and you often cannot make broad generalizations.

GutBrainAxis said:
The FMT option is obviously way way way less convenient than just taking pills that contain probiotics.
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Why? Both involve swallowing capsules. https://humanmicrobiome.info/fmt/

GutBrainAxis said:
I'm even willing to do FMT, but I have no idea where I'll get the money for that. I'm not sure what the whole process is that you have to go through in order to get FMT.
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It used to be easy, but now you'll have to read the blogs and get involved: https://forum.humanmicrobiome.info/threads/the-fda-and-fmt-regulation-part-2-jul-2024-humanmicrobes-org-i-met-wit.520/

If the FDA approves it your insurance might cover it.

GutBrainAxis said:
What do you guys think about the strains included in this product?
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You would have to review the probiotic guide.
 
1: Anyone here heard of combining apple-cider vinegar with probiotics? Not sure if there's any experience showing that that combo can be useful. Or any science that would point toward a potential synergy there.

2: What explains the seemingly weird precariousness regarding the fact that a human is seeded with certain biota during birth (from the vagina? from any other location?) such that those born by C-section will have to deal with lifelong health issues? It seems to me like a weird precariousness; am I missing something? Why did Mother Nature make so much dependent on such a "dicey" process? What if the baby is born the standard way but somehow isn't seeded properly? It just seems weird that there's one chance to "hand off" the microbiota to the baby; that process of "handing off" the microbiota goes wrong, there's no second chance, correct?
 
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GutBrainAxis said:
1: Anyone here heard of combining apple-cider vinegar with probiotics? Not sure if there's any experience showing that that combo can be useful. Or any science that would point toward a potential synergy there.
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I tried apple cider vinegar once, with the idea that Acetobacter species are alpha-proteobacteria and therefore belong to a different part of the bacterial tree of life than nearly all other probiotics. And they are even part of the gut microbiomes of some species, particularly insects. I made sure to get a "live" one that says it still contains the "mother", which is supposed to be a soft disc-like colony of microbes sitting in the bottom. After pouring off most of the vinegar (to get rid of excess organic acids, particularly acetic acid which I suspect are a stressor rather than a help), I unfortunately couldn't find any solid mass at the bottom that I could strain out and take. I tried adding a bit of the liquid to water and drinking it, if anything it made my gut worse. I wouldn't recommend it.

GutBrainAxis said:
2: What explains the seemingly weird precariousness regarding the fact that a human is seeded with certain biota during birth (from the vagina? from any other location?) such that those born by C-section will have to deal with lifelong health issues? It seems to me like a weird precariousness; am I missing something? Why did Mother Nature make so much dependent on such a "dicey" process? What if the baby is born the standard way but somehow isn't seeded properly? It just seems weird that there's one chance to "hand off" the microbiota to the baby; that process of "handing off" the microbiota goes wrong, there's no second chance, correct?
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When humans evolved, C-sections were nowhere near being a thing. That said, I don't think it matters so much how a baby is born as long as he/she has close physical contact with other healthy human beings during the first few months of life when the gut is getting colonized. Bacteria can be transferred through the mouth if the mother kisses them, from the skin when the baby nurses, etc. It's possible that vaginal microbiota are one of the best sources but I doubt it's the only source. And maybe we will find a way to expose even babies born via C-section to those--I mean it likely isn't that hard, the biggest barrier is probably squeamishness.

There's also it seems a natural tendency for very young kids to be curious about other kids and touch and lick each other, share food, etc., with a lack of physical boundaries that is only seen among couples in adults. It's the adults telling kids to NOT be "dirty" that puts a stop to this (and given that there ARE real serious infectious diseases out there, and were even more before vaccines were a thing, this adult behavior has at least a grain of truth behind it as well). So it could well be that children evolved to expose themselves to a wide variety of human-derived microbes as a kid, so even if their parents are ill they still have a chance to pick up healthy flora. The fact that most kids do start life out healthy, and most of our health issues start out after a disruption (a long course of antibiotics, an infection, or possibly just the developmental changes of adolescence) suggests that in fact most of us DO start out with an OK microbiota, it just gets damaged later.

I do agree that it's harder to re-colonize the gut with the right microbes after it already HAS microbes than it is to colonize it the first time at birth--this is just a function of "nature abhors a vacuum". There's probably no way around that, except to have a super immune system that is perfect at letting health microbes in and kicking unhealthy ones out, which is likely just a really hard problem that evolution can't possibly "master" once and for all.
 
1: What do you guys think about this? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10389721/

2: And this?
The active ingredients in ButyraGen® are tributyrin, a butyrate generator, and partially hydrolyzed guar fiber, a short chain fatty acid generator. Tributyrin is broken down in the gut by enzymes to generate high levels of the postbiotic butyrate. Butyrate is then available in the lumen. Butyrate plays an important role in intestinal barrier function and gut health, while also modulating immune and inflammatory responses. Receptors for butyrate are present in most cells in the body. Butyrate is also critical for the effects of the gut system on other organs (e.g. gut-brain axis, gut-skin axis, etc.).
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3: If a given probiotic only benefits you by creating a certain SCFA, is just supplementing that SCFA (by taking a "postbiotic") a superior option?
 
Tributyrin alleviates gut microbiota dysbiosis to repair intestinal damage in antibiotic-treated mice
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Sounds too good to be true. It's found in butter, and I and millions of other people eat plenty of butter and it hasn't done anything special for me/us.

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No, it's covered in the wiki. You can't simplify microbes down to a single function.
 
1: Is there any science (or speculation) that might explain the below scenario?

--someone is taking a couple basic probiotics (Align and Culturelle) and doing extremely well thanks to those probiotics
--the person suddenly undergoes a "collapse" where they lose all the wonderful health benefits that they were getting from the two probiotics
--the person suddenly regains the wonderful health benefits after doubling their dose of Align and Culturelle

2: Is it possible that fluctuations in gut motility might cause people to have to radically change their dose of a given probiotic over time in order to maintain a consistent effect? I mean, gut-motility change means a change in the rate at which a given bacteria either (A) leaves the body or else (B) leaves the location that the bacteria needs to be at in order to work.

Fmt2024 said:
Positive testimonial for FMT used to treat depression.

https://youtu.be/as5Wb7zSwqc?si=X1ofNuT2dAAevCoV
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What was your whole FMT experience? I didn't realize that FMT just involved taking pills; it seems like something that anyone could do as opposed to some "procedure" that involves that putting something into the non-mouth end of the GI tract.
 
I sometimes have these insane (absolutely INSANE) "collapses". I wonder whether phages might cause these collapses ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8764184/ ).

1: Phages might be responsible for a lot of people's dysbiosis, right?

2: But aren't people kind of screwed in the year 2024 when it comes to dealing with phage issues given how little is known about phages?
 
GutBrainAxis said:
1: Phages might be responsible for a lot of people's dysbiosis, right?
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Phages are part of the (normal) microbiome, so they're not by themselves the cause of dysbiosis or any disease. The cause of dysbiosis is essentially always either 1) excessive antibiotics, or 2) an infection of some kind (many people apparently get IBS after a bad bout of food poisoning). Some of us may be missing phages in addition to missing bacteria.

GutBrainAxis said:
2: But aren't people kind of screwed in the year 2024 when it comes to dealing with phage issues given how little is known about phages?
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You could say much the same about bacteria that live in the gut. Yes, we have given scientific species names to a large fraction of them, but how they interact is little known, and particularly importantly, it's not like you can just go and buy any of them.
 
Regarding treatment of dysbiosis, what are the implications of the bold part below?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300896/
Interestingly, several studies have indicated that the outer membrane compounds of A. muciniphila, or pasteurized bacteria, have greater therapeutic potential for metabolic, inflammatory, and autoimmune diseases than live A. muciniphila (36–38). Notably, Kang et al. (2013) reported a change in the composition of EVs in the feces of mice with DSS-induced UC, such as a decrease in the EVs of A. muciniphila and Bacteroides acidifaciens. In the same study, OMVs from A. muciniphila (AmOMV) suppressed the production of IL-6 in colonic epithelial cells (CT26 cell line) stimulated with OMVs from Escherichia coli in vitro, and oral administration of AmOMV, but not viable bacteria, attenuated DSS-induced colitis in vivo (36). Additionally, in a murine model of high-fat diet (HFD)–induced intestinal dysbiosis, AmOMVs improved the intestinal mucosal barrier function, increased the expression of TJs and IL-10, and inhibited inflammatory markers in the colon. AmOMVs are also able to reduce intestinal permeability, increase the expression of TJs via AMP-activated protein kinase (AMPK), inhibit TLR-4 and interferon-alpha (IFN-α) expression, and increase TLR-2 expression and IL-4 production in Caco-2 cell lines in vitro (39, 40). These data indicate that A. muciniphila components and their OMVs may be potential therapeutic targets for IBD.
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How often do people use this type of probiotic? I hadn't heard of it.

https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1304232/full

In this study, we used B. acidifaciens to interfere with dextran sulfate sodium (DSS)-induced colitis in mice, revealing its anti-inflammatory and barrier protection effects on enteritis mice. The effects of B. acidifaciens-mediated microorganisms and their metabolites on alleviating the symptoms of enteritis mice were confirmed by fecal bacteria transplantation (FMT) and aseptic fecal filtrate transplantation (FFT). Finally, we found that EVs of B. acidifaciens can inhibit inflammatory reactions, repair the intestinal mucosal barrier, and finally alleviate colitis in mice. Through proteomic analysis, it was confirmed that the functional proteins of B. acidifaciens and B. acidifaciens-EVs were different.
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I think that someone already linked to the below paper previously. But is the idea that you must continuously take probiotic pills because otherwise the effect will be temporary?

https://www.cell.com/cell/fulltext/S0092-8674(18)31102-4

Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.
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What are the "new personalized probiotic approaches" exactly?

https://www.cell.com/cell/fulltext/S0092-8674(18)31102-4

empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.
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I was just reading about probiotics. Just a couple questions. I know I just posted a few things; my apologies for posting so much. You can glue all my posts together if that's desirable.

1: I read this ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300896/): "Interestingly, several studies have indicated that the outer membrane compounds of A. muciniphila, or pasteurized bacteria, have greater therapeutic potential for metabolic, inflammatory, and autoimmune diseases than live A. muciniphila (36–38)." Am I understanding correctly that the pasteurization process means that you will be ingesting (when you ingest the pasteurized product) the "outer membrane compounds" of the bacterium? And when will it be possible to get such products, assuming that the difference is actually significant?

2: A long time ago I saw a scientific article that went into detail about the microbiota-composition abnormalities associated with all of the various psychiatric conditions. One might imagine that you could look at that paper, find the bacteria that seem to be low in patients who have the same diagnoses that you do, and then supplement those bacteria. Do you guys know of any papers like that? I read this paper ages ago, it seems. There are probably some really good reviews looking at the various psychiatric diseases and the associated abnormalities.

3: I can understand the appeal of FMT. It seems much more intelligent to just transplant a healthy person's microbiome than to try to tinker with your own, right?

4: What is the best review that tackles the issue of what the "keystone" species of bacteria might be regarding human dysbiosis? I'm asking because it makes sense to try to find out what the "keystone" species are as opposed to tinkering with all sorts of non-"keystone" species.

5: What is the best review that goes through all of the non-standard probiotics that one might try? The below paragraph names some non-standard probiotics, but I wonder if there's a review that comprehensively lists the non-standard ones. See here:

There are a FEW other bacteria represented--like various Bacillus species, a few Clostridia (found in Pendulum brand probiotics only), Akkermansia muciniphila (again Pendulum only) a few strains of E. coli (Nissle, Symbioflor) you need to order from Europe to get, most recently a strain of Propionibacterium (the bacteria that make holes in Swiss cheese) and the soil-based bacteria Michael mentioned (the Bacillus species are soil bacteria too--however there are many OTHER soil-dwelling organisms found in a true "soil based" probiotic like Prescript-Assist). And there are yeast, you mention Saccharomyces boulardii, which is really just a special strain of ordinary baker's/brewer's yeast, S. cervisiae. While somewhat more diverse, again there's the caveat that (with the possible exception of Akkermansia), there's no reason to believe that these are major keystone species lost from the gut when you take antibiotics and whose absence is the cause of the "missing microbes" phenomenon.
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1: What does everyone think of the products discussed here ( https://www.healthline.com/nutrition/seed-probiotics-review )?

2: The review that I just linked mentions various bacteria that I hadn't ever heard of. Are all of the ones below worth trying? And which of the ones listed below are actually unusual or "exotic"?

Bifidobacterium longum SD-BB536-JP, Bifidobacterium breve SD-BR3-IT, Lactiplantibacillus plantarum SD-LP1-IT, Lacticaseibacillus rhamnosus SD-LR6-IT, Lacticaseibacillus rhamnosus HRVD113-US, Bifidobacterium infantis SD-M63-JP, Bifidobacterium lactis SD-BS5-IT, Bifidobacterium lactis HRVD524-US, Lactobacillus crispatus SD-LCR01-IT, Lacticaseibacillus casei HRVD300-US, Bifidobacterium breve HRVD521-US, Bifidobacterium longum HRVD90b-US, Bifidobacterium lactis SD150-BE, Limosilactobacillus fermentum SD-LF8-IT, Lacticaseibacillus rhamnosus SD-GG-BE, Limosilactobacillus reuteri RD830-FR
Ligilactobacillus salivarius SD-LS1-IT, Bifidobacterium lactis SD-CECT8145-SP, Bifidobacterium longum SD-CECT7347-SP, Lacticaseibacillus casei SD-CECT9104-SP
Lactiplantibacillus plantarum SD-LPLDL-UK, Bifidobacterium lactis SD-MB2409-IT
Bifidobacterium adolescentis SD-BA5-IT, Limosilactobacillus reuteri SD-LRE2-IT
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A few more things. Sorry to stack so many things up.

1: I found this paper to be very impressive and interesting: https://www.sciencedirect.com/science/article/pii/S0278584623001471. Do you guys also find it to be an excellent paper?

2: Are any useful probiotics mentioned in the paper that aren’t yet available for consumers to purchase?

3: Is the type of probiotic talked about in this ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787120/ ) paper worth trying?

4: Why would it make sense to supplement Akkermansia instead of just supplementing other bacteria whose presence will then lead to an increase in one's levels of Akkermansia?

5: What do you guys think of this video that talks about Akkermansia? https://www.youtube.com/watch?v=c656V9omekw

6: There's no way to know which one will be more effective for you if a given probiotic product comes in two different "strengths", right? It looks like this ( https://nowfoods.ca/product/probiotic-10-25-billion/ ) product comes in a 25 billion, a 50 billion, and a 100 billion "strength". It's just a matter of trial and error if you want to find out which one works best, since there are unpredictable dynamics that might make one "strength" too "weak" and another "strength" too "strong", correct?

7: Not sure if it's known for certain that there is indeed a parabola for every single probiotic product when it comes to "strength", but if there is in fact a parabola for a given product then it's unpredictable where the optimum of the parabola (past which the product is less effective because it's too "strong") is, correct?

8: What do you guys think about the importance of trying a "rainbow strategy" where you take 5 different probiotic products all at once? Is there a possible "synergy" that might be unlocked when you take a "rainbow" of 5 different pills at once? The "rainbow" strategy seems like it might work.

9: Is this ( https://aor.ca/product/postbiotic-boost/ ) product worth trying, do you think?

Is it possible to purchase any of the below-mentioned probiotics?

https://www.intechopen.com/chapters/88819

Autism spectrum disorder (ASD) is a disorder characterized by social and behavioral impairment. In addition to neurological symptoms, the patient often suffers from gastrointestinal abnormalities. Some microbial species have been linked to the pathogenesis of this disease; symptoms have been linked to a reduction of Pretovella, Coprococcus, Veillonellaceae, and Bracteroides fragilis and a reduction in the availability of TPH [6, 14].
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And how many of the probiotics mentioned in this ( https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1103836/full ) review, including the ones in this ( https://www.frontiersin.org/files/Articles/1103836/fmicb-13-1103836-HTML/image_m/fmicb-13-1103836-t001.jpg ) table, can be purchased?

I wonder how many of these ( https://www.frontiersin.org/files/Articles/1103836/fmicb-13-1103836-HTML/image_m/fmicb-13-1103836-t003.jpg ) strains are purchasable. And I also wonder about the ones mentioned below:

https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1103836/full

Butyrate-producing gut microbes are of significant therapeutic importance and are believed to be niche-specific next-generation probiotics. Multiple butyrate-producing probiotic strains of Clostridium butyricum (Stoeva et al., 2021) and Butyricicoccus pullicaecorum (Geirnaert et al., 2014; Boesmans et al., 2018) have been used as they exhibit good bile tolerance, viability, and metabolic activity (Table 3). Microbes of interest or butyrate producers can also be genetically manipulated to increase their butyrate-producing capacity. For example, heterologous genes required for butyrate production from acetyl-CoA can be introduced by inactivating the gene encoding the conversion of acetyl-CoA to acetate and the gene encoding the aldehyde/alcohol dehydrogenase for ethanol production or simply disrupting a CoA transferase gene, which may be an alternative route for acetate production (Ueki et al., 2014; Suo et al., 2018). Additionally, a co-culture strategy, that is an interactive microbial population of more than two microbes, can also be implemented to achieve higher levels of butyrate and increased abundance of butyrate producers in the gut. Co-culture of F. prausnitzii and Bifidobacterium catenulatum with fructooligosaccharides as an energy source resulted in a higher viable cell count and butyrate production (Kim et al., 2020). Moreover, butyrate producers of animal origin (ruminants), such as cellulose-degrading Ruminococcus albus and R. flavefaciens (Flint et al., 2008; Chassard et al., 2012), can also be considered to study their impact on human hosts.
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Regarding this ( https://aor.ca/product/probiotic-3/ ) product, why is the ratio so skewed? One of the strains is present to a far higher degree than the other two; one strain is more than 18 times (!!!) more abundant in the product than the other two, which is striking to me.

Lastly, two things about this ( https://pendulumlife.com/blogs/news/what-is-clostridium-butyricum ) product.

1: Pendulum doesn't seem to sell it anymore. I contacted them asking if they no longer sell it and why they stopped selling it.

2: What do you guys make of the fact that this product "contains 15 million AFU of Clostridium butyricum, a powerful bacillus strain naturally found in the human gut"? I read that on another website, not Pendulum's. If it contains 15 million AFU then that's more than 15 times as much as the AOR product ( https://aor.ca/product/probiotic-3/ ) that only contains 0.6 million AFU of that same type of bacteria. It's such a huge difference; I wonder what you guys make of that.
 
GutBrainAxis said:
How often do people use this type of probiotic? I hadn't heard of it.
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There are various bacteria used in studies that haven't made it to products yet. Often due to conflicting or lack of evidence, or difficulty mass producing.

GutBrainAxis said:
is the idea that you must continuously take probiotic pills because otherwise the effect will be temporary?
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That's usually the case.

GutBrainAxis said:
Am I understanding correctly that the pasteurization process means that you will be ingesting (when you ingest the pasteurized product) the "outer membrane compounds" of the bacterium? And when will it be possible to get such products
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Pasteurization just kills the bacteria. "When will it be available" is not answerable.

GutBrainAxis said:
I can understand the appeal of FMT. It seems much more intelligent to just transplant a healthy person's microbiome than to try to tinker with your own, right?
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Currently, there are severe limits to how much you can tinker with your own. FMT is much more powerful than any other intervention.

GutBrainAxis said:
it makes sense to try to find out what the "keystone" species are as opposed to tinkering with all sorts of non-"keystone" species.
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There is little a layperson could do with that info.

GutBrainAxis said:
I wonder if there's a review that comprehensively lists the non-standard probiotics
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You could try searching "next gen probiotics".

GutBrainAxis said:
What does everyone think of the products discussed here (Seed probiotic)
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Seed spends a lot of money on marketing. Their product, and the experiences I've read, don't impress me.

GutBrainAxis said:
Are the probiotics below worth trying?
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It's all highly experimental. Nearly all of your questions are answered in the probiotic guide https://humanmicrobiome.info/probiotic-guide. For others, you'll have to search the web or ask the manufacturer.
 
 
What do you guys think about the cocktail that is mentioned below? And is that cocktail at all close to being available to consumers?

https://www.mdpi.com/2076-2607/12/8/1627

Taken together, the findings from this study demonstrate that the co-occurrence of A. muciniphila with other gut bacterial clades, including Desulfovibrio, Family XIII AD3011 group, and Candidatus Saccharimonas confers beneficial effects on host gut and cardiometabolic health through different molecular pathways and mechanisms. For instance, A. muciniphila and its protein derivatives can regulate TLR signaling, remodel the mucin layer, and provide sulfur sources for Desulfovibrio. Desulfovibrio may provide physiological levels of H2S, which is beneficial for the cardiovascular system, while Candidatus Saccharimonas may provide SCFAs like lactate and acetate. Thus, it is likely that a probiotic consortium containing these four gut bacterial genera would be more effective in a wide range of inflammatory diseases.
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Pendulum started selling an A. muciniphila probiotic just a year or two ago. Candidatus Saccharimonas has not even been cultured, let alone commercialized, it's only known to exist by its DNA sequence that has been caught floating around in samples. Nobody even knows what the cells look like, though they are almost certainly very small (even for bacteria). Desulfovibrio is generally regarded as not that beneficial, in fact most labs that do gut testing will warn you if you have a large amount of Desulfovibrio that you might have dysbiosis.

To add to that, the fact that these (as a community) may be beneficial for cardiovascular health in no way implies that they would also be beneficial for neuropsychiatric health.
 
Thanks for the excellent points. I appreciate it.

1: If you don't mind me asking, what are your credentials? You seem to have professional knowledge.

2: What do you think about Pendulum's products? Some of their products seem to be redundant. I think that the "Metabolic Daily" one contains literally all of their strains, though I could be wrong. I want to try the "Metabolic Daily" one and also their product that is just Akkermansia.

3: How long a trial is necessary regarding the Pendulum products, though?

4: How long till the strains that Pendulum sells are available from various companies? It's not like the strains are proprietary. I can't wait till the Pendulum strains can be obtained more conveniently.

5: What are your favorite probiotics and supplements and drugs when it comes to improving gut health and brain health and general health? I know it's a broad question, but I'm curious, since you seem to know a lot.

6: Do you by chance happen to know a lot about melatonin? And about agomelatine? I know it's random to ask about this domain, but I'm just curious.
 
1. I have a degree in biochemistry and work in a neurobiology lab, and I've also looked into a lot of things as possible treatments for my own condition (which is some sort of neuro-immune condition that has never been formally diagnosed, though I see similarities to experiences of families with PANS https://pansaustralia.com/what-is-pans-pandas/--the original infection was Lyme disease but the antibiotic treatment for that is what really made my health go downhill).

2. I don't have any opinion on Pendulum's products in terms of effectiveness, I've never tried any of them and don't know anyone who has. They DO have some unique bacteria that aren't found in other probiotics, which makes them at least somewhat worthy of respect. In the world of probiotics, 90% of them are in one of two genera (Lactobacillus and Bifidobacterium), and they are differentiating themselves on specific strains within that, but relative to the diversity of bacteria on Earth that whole world is SUPER tiny.

It's like someone is trying to restore a wasteland to a forest and everyone is selling him ferns. One of them says "well my fern has fronds that are 20% longer than the ones this other guy is selling you"--but it's still just a fern. Where are the conifers? the mosses? the shrubs? So whenever someone sells a completely different kind of plant, that's putting them in a class apart from the rest, which most companies in this area are afraid to/don't care to do.

3. Who knows?

4. It seems most companies aren't willing to stick their necks out to set up a culture system for these bacteria, have testing to be sure they are not contaminated with other microbes, etc. Particularly when they can sell other, more readily available bacteria to the masses of people looking for a digestive aid. At least there's a company you can order them from--if you're interested in trying them why not order? It's still much cheaper and easier to obtain than FMT!

5. No probiotics have really made a noticeable dent in either my gut symptoms (food sensitivities, pain, etc.) or my neuropsychiatric symptoms. There is one strain of E. coli that you need to order from Germany (Symbioflor 2) that helped a bit more than the usual probiotics, but not decisively so. Again, this is in a totally different group of probiotics than the typical ones. And none even comes CLOSE to a FMT--particularly the OpenBiome FMT I got in the hospital, which was ostensibly to treat C. diff, but which radically improved much more, the neuropsychiatric changes being the most dramatic.

As far as non-probiotic supplements, again very few made a significant difference, and NONE have made a difference when I was at my worst. By far the most impactful supplement I've ever taken is the serotonin precursor 5-HTP, which improved mood, concentration, and even gut motility very significantly when I started it. However, this was started AFTER my first FMT had already brought me a good part of the way back to normal, and even THAT eventually (after ~9 months) ended up making things worse, driving me toward a weird manic-like state with almost psychotic-like feelings of unreality.

The takeaway of all this is, if you have a dysbiotic gut, it can make any other treatment you do "hit a wall". You eventually get to the point where everything makes you worse, because you're effectively trying to make your system "run on empty". You can find things that maybe give you a temporary "high" but eventually everything will crash. Like if you're starving, you can maybe fill your stomach with something other than food so you don't feel hungry, you can drink coffee to artificially raise your energy, but eventually it will catch up with you because a fundamental need is going unmet. One of the signs of starting to restore my gut health is that I can actually tolerate and benefit from more supplements.

6. Melatonin is like a placebo for me--it does absolutely nothing. I haven't tried agomelatine, but my mom, who has had insomnia for decades, tried ramelteon (another melatonin agonist) and it made her very depressed while not helping her insomnia at all. She and I both have much better success for sleep with antihistamine-type drugs, when those don't work then benzodiazepines are the only thing that works. For depression, I'd recommend 5-HTP greatly over melatonin (and 5-HTP could help produce melatonin as well, since it's also a precursor of that--but melatonin can't convert BACK to help with serotonin levels). For dopamine and norepinephrine, taking tyrosine helps--though I have the opposite issue (tending for dopamine/norepinephrine to exceed serotonin) so for me it is not helpful to take tyrosine.
 
1: I get a huge reaction from melatonin. That's why I'm interested in agomelatine, which apparently has a superior melatonin-receptor effect to melatonin's, though I can't remember what exactly the advantage is supposed to be.

2: Melatonin is a fascinating thing...see this paper here: https://pmc.ncbi.nlm.nih.gov/articles/PMC7694322/.

3: What advantages (if any) does 5-HTP supplementation have over tryptophan supplementation?

4: If 5-HTP was a huge help to you then it's very important that you find a way to get 5-HTP to work for you again, right?

5: What might have caused the 5-HTP to stop working? You can look at what events in your life coincided with the cessation of 5-HTP's effectiveness.

6: I experience a lot of "tachyphylaxis". But with me we're talking about a day or a week of effectiveness. I find it fascinating that something would work for months and then stop working; I wonder why the effect would be so stable and then suddenly disappear.

7: Any ideas as to why "Symbioflor 2" helped you so much?

8: What can I read on the possible explanations regarding why supplementation of tryptophan and of tyrosine helps people? Isn't your food supposed to contain tons of amino acids? What could yield a situation where you're eating a good diet and yet you somehow lack certain amino acids?

Just some extra questions regarding amino acids.

1: What about arginine? Is it worth trying?

2: What about various amino acids other than arginine, tyrosine, and tryptophan?

3: Is there any big review paper that talks about which amino acids are the most important ones to try? I mean, there are so many amino acids, so it would be great to know which ones to prioritize when it comes to trying supplements.

Is there anything I can read on the below concept?

The takeaway of all this is, if you have a dysbiotic gut, it can make any other treatment you do "hit a wall". You eventually get to the point where everything makes you worse, because you're effectively trying to make your system "run on empty". You can find things that maybe give you a temporary "high" but eventually everything will crash. Like if you're starving, you can maybe fill your stomach with something other than food so you don't feel hungry, you can drink coffee to artificially raise your energy, but eventually it will catch up with you because a fundamental need is going unmet. One of the signs of starting to restore my gut health is that I can actually tolerate and benefit from more supplements.
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1: Do you guys know a lot about butyrate and butyrate supplementation? See this excellent paper: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.893567/full. The paper says interesting things about butyrate, including the following:

SCFAs (including acetate, propionate and butyrate), which are typical anti-inflammatory molecules produced by the gut microbiota, can exert anti-inflammatory effects by inhibiting interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) expression through the FFAR2 (GPR43) receptor (Pirozzi et al., 2018). Animal studies have provided evidence on the effects of SCFAs on cognitive function through immunological pathways. The effects of butyrate on cognitive function have been described above. Additionally, decreased absolute concentrations of acetate, propionic acid, and butyrate lead to blood-brain barrier dysfunction, microglial activation, and elevated cortical IL-1β, IL-6, and TNF-α expression levels in mice maintained on a high-salt diet, exhibiting a reduced number of organisms in the Bacteroidetes and Proteobacteria phyla and an increased number of those in the Firmicutes phylum, respectively (Hu et al., 2020). Mice with a deficiency of the SCFA receptor FFAR2 showed global defects in microglia similar to those of germ-free mice, suggesting that the gut microbiota regulates microglia maturation and function (Borre et al., 2014; Erny et al., 2015). Microglia cells mediate neuroinflammation as the major innate immune cell population in the brain, playing an important role in the pathophysiology of BD (Maletic and Raison, 2014) and cognitive impairment (Feng et al., 2017; Zhao et al., 2019). However, to our knowledge, studies directly linking SCFAs to cognitive impairment in BD are still scarce. Indirectly, butyrate has been tested as a potential treatment for mood disorders, including BD and major depressive disorder, acting by controlling epigenetic programming associated with cognitive and behavioral regulation as a histone deacetylase inhibitor (Machado-Vieira et al., 2011). Lithium carbonate, one of the most commonly used drugs for treating BD, may activate anti-inflammatory regulatory T-cell responses through an FFAR2-dependent mechanism by altering the SCFA-producing gut microbiota (e.g., through upregulation of the butyric acid-producing bacterium Akkermansia muciniphila) to change SCFA profiles (Huang et al., 2022). With the support of some clinical studies, given the positive effects of lithium carbonate on cognitive functions, including memory and attention (Dias et al., 2012), disruption of the SCFA profile may impair cognitive function in BD patients through systemic inflammation. Marizzoni et al. (2020) found that both cognitive function and endothelial dysfunction in older adults are positively correlated with the pro-inflammatory cytokines acetate and valerate but negatively correlated with the levels of butyric acid and IL-10. The gut microbiota with reduced SCFA production can also trigger an intestinal inflammatory response and progression of Parkinson’s disease (Unger et al., 2016; Vascellari et al., 2020; Aho et al., 2021). Such clinical evidence suggests that SCFAs are involved in the development of cognitive impairment through systemic inflammation caused by endothelial dysfunction.
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2: I took some butyrate pills and something puzzling happened that I don't have an explanation for; I wonder if you guys can help me hypothesize about what might've happened. Basically I felt terrible for about two hours or so; I was mentally foggy and I had some mild nausea and I was very tired. I was lying in bed; I was about to go to sleep. Then suddenly I snapped out of it. Since I snapped out of it, I've been sharp and energetic and feeling great from head to toe. My mental visualization and my mental math aren't like blowing me away or anything but I need more time to evaluate just how strong I am in these domains right now. Any ideas as to what happened?

3: I guess that some process (that requires two hours) had to be completed before the butyrate could be helpful to me. Why did I feel so terrible during that process? Was the issue simply that the butyrate had to (e.g.) get past my small intestine? Was the process related to the butyrate's having to move from one location in my gut to another location in my gut?

4: I wonder if the butyrate was killing bad microbes in my gut. Why would the process of killing bad microbes cause me to feel so terrible for a couple hours? See here ( https://pmc.ncbi.nlm.nih.gov/articles/PMC7192831/ ):

An excessive hyperinflammatory response-caused septic shock is a major medical problem that is associated with pathogenic bacterial infections leading to high mortality rates. The intestinal microbiota and the associated elaborated metabolites such as short chain fatty acid butyrate have been shown to relieve pathogenic bacterial-caused acute inflammation. Butyrate can down-regulate inflammation by inhibiting the growth of pathobionts, increasing mucosal barrier integrity, encouraging obligate anaerobic bacterial dominance and decreasing oxygen availability in the gut. Butyrate can also decrease excessive inflammation through modulation of immune cells such as increasing functionalities of M2 macrophages and regulatory T cells and inhibiting infiltration by neutrophils. Therefore, various approaches can be used to increase butyrate to relieve pathogenic bacterial-caused hyperinflammation. In this review we summarize the roles of butyrate in attenuating pathogenic bacterial-caused hyperinflammatory responses and discuss the associated plausible mechanisms.
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I wonder if the bad feeling that I had had anything to do with mast cells. See here:

In summary, butyrate can affect above immune cells to exert anti-inflammatory effect through the various mechanisms such as HDAC inhibition and butyrate receptor activation. In addition to these cells, other immune cells are also affected by butyrate but less studied such as mast cells, dendritic cells and T cells. Mast cells are inflammatory immune cells, which produce various inflammatory factors including TNF-α, IL-6, histamine and tryptase. Butyrate can reduce mast cells to secret these pro-inflammatory factors through HDAC inhibition (75). It also inhibits dendritic cell maturation and function to secret pro-inflammatory factors IL-6 and TNF-α (76,77). Furthermore, butyrate causes T cell apoptosis through HDAC inhibition and associated cell death receptor Fas activation (78). Further studies are warranted to understand the effects of butyrate on these immune cells.
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GutBrainAxis said:
1: I get a huge reaction from melatonin. That's why I'm interested in agomelatine, which apparently has a superior melatonin-receptor effect to melatonin's, though I can't remember what exactly the advantage is supposed to be.
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It's also a 5-HT2C (one of the serotonin receptors, that plays a role in limiting the effectiveness of SSRIs) antagonist.
GutBrainAxis said:
2: Melatonin is a fascinating thing...see this paper here: https://pmc.ncbi.nlm.nih.gov/articles/PMC7694322/.

3: What advantages (if any) does 5-HTP supplementation have over tryptophan supplementation?
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There are multiple fates of tryptophan--being made into protein, acting as a NAD precursor, etc. 5-HTP can ONLY be used to make serotonin and melatonin. Provided that's what you need, having some tryptophan that is effectively "earmarked" for that purpose can make a tremendous difference.
GutBrainAxis said:
4: If 5-HTP was a huge help to you then it's very important that you find a way to get 5-HTP to work for you again, right?
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All that's important is to get well, one way or another.
GutBrainAxis said:
5: What might have caused the 5-HTP to stop working? You can look at what events in your life coincided with the cessation of 5-HTP's effectiveness.
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It didn't "stop working" (in the sense of developing tolerance)--it went from providing a productive, calm, focused, happy state to an almost derealized dysphoric state with awful executive function, somewhat along the lines of a weird type of mania (but not the hyper-productive energetic kind). When I stopped taking it, I felt significantly more depressed for a month or so, but then that went away. I'm still in the process of trying to get out of that dysphoric, reality-detached state I was in, through FMT.

The fact that it was so beneficial in the beginning, and then these other effects slowly crept in over more than a year, made it if anything more insidious, because it was difficult to perceive the change and to realize that I was going downhill. My life was also at a turning point where my next direction was uncertain--that contributed to allowing this descent to continue without me fully being cognizant of it and searching for causes.

An analogy I'd use is, say you had gone years eating a severely deficient diet, and being sick as a result. Then you realized you were low in vitamin B1, and started taking it. The B1 deficiency symptoms might disappear within days, which would seem like a miracle, but you still have lots of other deficiencies. Some of those would likely cause MORE symptoms now that the B1 is normal, because at least before the nutrients were somewhat in balance relative to each other, just low, but now the processes using vitamin B1 are going too fast relative to all the other processes, causing more pressure on those other pathways as they try to keep up. That's my best way of conceptualizing what happened.

GutBrainAxis said:
7: Any ideas as to why "Symbioflor 2" helped you so much?
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It didn't help "so much"--it actually did SOMETHING positive, which is more than can be said of all the lactic acid bacteria I've tried. It was not any kind of "game changer" though. This difference is likely due to having many more metabolic pathways (E. coli can grow on almost anything organic--not JUST sugars, or amino acids, or whatever).
GutBrainAxis said:
8: What can I read on the possible explanations regarding why supplementation of tryptophan and of tyrosine helps people? Isn't your food supposed to contain tons of amino acids? What could yield a situation where you're eating a good diet and yet you somehow lack certain amino acids?
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The problem is likely in your body's ability to divert the amino acids to the proper pathways. That's why having something like 5-HTP (or L-DOPA for the tyrosine-derived neurotransmitters) can be much more helpful than the amino acids themselves.
 
1: I took some 5-HTP last night and it made a huge (!!!) difference. I really hope that this quite miraculous improvement doesn't go away.

2: When was the last time you took some 5-HTP? Baffling to me why it stopped working for you; hope you can get the effect back.

3: What can one say about the difference between blocking reuptake of serotonin (with escitalopram, say) and supplementing 5-HTP? How are those two approaches equivalent and how are they different?

4: I know someone who took some 5-HTP while at a music festival; people use 5-HTP in order to combat the bad effects of the recreational drugs that they take at music festivals or something. It wasn't a big dose of 5-HTP apparently and it was apparently the exact same dose that everyone else took, but for some reason the 5-HTP induced serotonin syndrome in this person. Can you think of any reason why that might occur? It's a weird phenomenon to consider but it also might say something about what this person should do in order to improve their brain function.

5: Are there good studies on how effective 5-HTP and L-DOPA supplementation are when it comes to treating psychiatric symptoms? I wonder what the statistics show when it comes to using 5-HTP and L-DOPA to treat psychiatric symptoms.

6: Is L-DOPA actually gettable as a supplement?

7: Why does it seem like L-DOPA is harder to obtain than 5-HTP?

8: Why can't my body just send the tryptophan into my brain? And why can't my brain then make serotonin from the tryptophan? Maybe I have an issue with this: https://en.wikipedia.org/wiki/TPH1. Or with this: https://en.wikipedia.org/wiki/TPH2.

9: I hope that I don't have any issue with BH4 ( https://en.wikipedia.org/wiki/Tetrahydrobiopterin ) because that sounds tricky to deal with.

10: Apparently BH4 issues are super rare. What are the odds that I have an issue with BH4?
 
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