Serotonin Production (gut) Depends On Bacteria

haidut

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I think this study may finally answer why Peat favors the germ free gut. In addition, in light of the recent study I posted that inhibiting gut serotonin cures obesity, this study essentially suggests that things like charcoal, carrot and antibiotics can be used for weight loss purposes since they all inhibit (kill) gut bacteria.
So, for anybody still having questions about how to balance the gut microbiome - the answer is you don't. The more germ free you keep your gut, the lower your peripheral serotonin levels will be, the higher your metabolism will be and the healthier you will be.
The study also says that specific microbial metabolites also stimulate gut serotonin production. I will try to get the full study and see what those metabolites are. For the people feeling ambivalent about keeping their gut sterile, the more acceptable option may be to reduce those metabolites and not mess with the bacteria directly. The study says that inhibiting those metabolites also reduces serotonin production.

http://scicasts.com/disease-processes/2 ... in-in-gut/
http://www.cell.com/abstract/S0092-8674%2815%2900248-2

"...Although serotonin is well known as a brain neurotransmitter, it is estimated that 90 percent of the body's serotonin is made in the digestive tract. In fact, altered levels of this peripheral serotonin have been linked to diseases such as irritable bowel syndrome, cardiovascular disease, and osteoporosis."

"...Researchers at Caltech have now found that certain bacteria in the gut are important for the production of peripheral serotonin. They reported their findings in the April 9 issue of the journal Cell."

"...Peripheral serotonin is produced in the digestive tract by enterochromaffin (EC) cells and also by particular types of immune cells and neurons. Hsiao and her colleagues first wanted to know if gut microbes have any effect on serotonin production in the gut and, if so, in which types of cells. They began by measuring peripheral serotonin levels in mice with normal populations of gut bacteria and also in germ-free mice that lack these resident microbes."

"...The researchers found that the EC cells from germ-free mice produced approximately 60 percent less serotonin than did their peers with conventional bacterial colonies. When these germ-free mice were recolonized with normal gut microbes, the serotonin levels went back up--showing that the deficit in serotonin can be reversed."

"...EC cells are rich sources of serotonin in the gut. What we saw in this experiment is that they appear to depend on microbes to make serotonin--or at least a large portion of it," says Jessica Yano, first author on the paper and a research technician working with Hsiao."

"...After testing several different single species and groups of known gut microbes, Yano, Hsiao, and colleagues observed that one condition--the presence of a group of approximately 20 species of spore-forming bacteria--elevated serotonin levels in germ-free mice. The mice treated with this group also showed an increase in gastrointestinal motility compared to their germ-free counterparts, and changes in the activation of blood platelets, which are known to use serotonin to promote clotting."

"...Wanting to home in on mechanisms that could be involved in this interesting collaboration between microbe and host, the researchers began looking for molecules that might be key. They identified several particular metabolites--products of the microbes' metabolism--that were regulated by spore-forming bacteria and that elevated serotonin from EC cells in culture. Furthermore, increasing these metabolites in germ-free mice increased their serotonin levels."

"...Previous work in the field indicated that some bacteria can make serotonin all by themselves. However, this new study suggests that much of the body's serotonin relies on particular bacteria that interact with the host to produce serotonin, says Yano. "Our work demonstrates that microbes normally present in the gut stimulate host intestinal cells to produce serotonin," she explains."
 

jyb

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haidut said:
I think this study may finally answer why Peat favors the germ free gut. In addition, in light of the recent study I posted that inhibiting gut serotonin cures obesity, this study essentially suggests that things like charcoal, carrot and antibiotics can be used for weight loss purposes since they all inhibit (kill) gut bacteria.

Does charcoal really kill bacteria (affect bacteria count)? I know it's a very powerful toxin cleaner.
 
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haidut

haidut

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jyb said:
haidut said:
I think this study may finally answer why Peat favors the germ free gut. In addition, in light of the recent study I posted that inhibiting gut serotonin cures obesity, this study essentially suggests that things like charcoal, carrot and antibiotics can be used for weight loss purposes since they all inhibit (kill) gut bacteria.

Does charcoal really kill bacteria (affect bacteria count)? I know it's a very powerful toxin cleaner.

This study says that it does not kill bacteria but it binds it and helps remove it from the body:
http://www.ncbi.nlm.nih.gov/pubmed/3052639
 

jyb

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haidut said:
jyb said:
haidut said:
I think this study may finally answer why Peat favors the germ free gut. In addition, in light of the recent study I posted that inhibiting gut serotonin cures obesity, this study essentially suggests that things like charcoal, carrot and antibiotics can be used for weight loss purposes since they all inhibit (kill) gut bacteria.

Does charcoal really kill bacteria (affect bacteria count)? I know it's a very powerful toxin cleaner.

This study says that it does not kill bacteria but it binds it and helps remove it from the body:
http://www.ncbi.nlm.nih.gov/pubmed/3052639

Same effect then. Maybe a few days of charcoal can be used as a safe (and easy to obtain over the counter) antibiotic instead of the usual drugs.
 
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haidut

haidut

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jyb said:
haidut said:
jyb said:
haidut said:
I think this study may finally answer why Peat favors the germ free gut. In addition, in light of the recent study I posted that inhibiting gut serotonin cures obesity, this study essentially suggests that things like charcoal, carrot and antibiotics can be used for weight loss purposes since they all inhibit (kill) gut bacteria.

Does charcoal really kill bacteria (affect bacteria count)? I know it's a very powerful toxin cleaner.

This study says that it does not kill bacteria but it binds it and helps remove it from the body:
http://www.ncbi.nlm.nih.gov/pubmed/3052639

Same effect then. Maybe a few days of charcoal can be used as a safe (and easy to obtain over the counter) antibiotic instead of the usual drugs.

Charcoal does a lot more than remove bacteria and toxins. It stimulates liver and kidney function and helps the body protects itself from endotoxin. So, unless you need real antibiotic to handle infection I'd say charcoal is preferable to antibiotics for intestinal health.
Here is something from Peat:
http://raypeat.com/articles/nutrition/carrageenan.shtml

"...I have previously discussed the use of antibiotics (and/or carrot fiber and/or charcoal) to relieve the premenstrual syndrome, and have mentioned the study in which the lifespan was extended by occasionally adding charcoal to the diet. A few years ago, I heard about a Mexican farmer who collected his neighbors' runt pigs, and got them to grow normally by adding charcoal to their diet. This probably achieves the same thing as adding antibiotics to their food, which is practiced by pig farmers in the US to promote growth and efficient use of food. Charcoal, besides binding and removing toxins, is also a powerful catalyst for the oxidative destruction of many toxic chemicals. In a sense, it anticipates the action of the protective enzymes of the intestinal wall and the liver."

Given the many benefits of charcoal on the detox system, it is not surprising that charcoal is actually approved as a drug for end-stage kidney disease.
http://www.eurekalert.org/pub_releases/ ... 102009.php
http://www.ncbi.nlm.nih.gov/pubmed/23689670
http://www.ncbi.nlm.nih.gov/pubmed/20061701
 

jyb

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haidut said:
"...I have previously discussed the use of antibiotics (and/or carrot fiber and/or charcoal) to relieve the premenstrual syndrome, and have mentioned the study in which the lifespan was extended by occasionally adding charcoal to the diet. A few years ago, I heard about a Mexican farmer who collected his neighbors' runt pigs, and got them to grow normally by adding charcoal to their diet. This probably achieves the same thing as adding antibiotics to their food, which is practiced by pig farmers in the US to promote growth and efficient use of food. Charcoal, besides binding and removing toxins, is also a powerful catalyst for the oxidative destruction of many toxic chemicals. In a sense, it anticipates the action of the protective enzymes of the intestinal wall and the liver."

A catalyst to toxin destruction...I wonder why charcoal in particular would do that. A provider of carbon for a chemical reaction? Wikipedia on charcoal:
Carbon source[edit]
Charcoal may be used as a source of carbon in chemical reactions. One example of this is the production of carbon disulphide through the reaction of sulfur vapors with hot charcoal. In that case the wood should be charred at high temperature to reduce the residual amounts of hydrogen and oxygen that lead to side reactions.
 

Dean

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This sterile gut thing just doesn't make sense to me. Sure, if we all could live in the land of milk and honey (mmm,yum)--where all our food sources were immaculate and food suppliers could be trusted. Or, if we could live in a clinical vacuum (or test tube)--though I'm not sure why anyone would want to. But given the real world, our degraded food supply and the stark reality that it is only going to get worse...much worse, I just don't get how it will work. In fact, I would argue a lot of the problem with our food supply (in the developed world) is it has become too sterile already.
 
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haidut

haidut

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jyb said:
haidut said:
"...I have previously discussed the use of antibiotics (and/or carrot fiber and/or charcoal) to relieve the premenstrual syndrome, and have mentioned the study in which the lifespan was extended by occasionally adding charcoal to the diet. A few years ago, I heard about a Mexican farmer who collected his neighbors' runt pigs, and got them to grow normally by adding charcoal to their diet. This probably achieves the same thing as adding antibiotics to their food, which is practiced by pig farmers in the US to promote growth and efficient use of food. Charcoal, besides binding and removing toxins, is also a powerful catalyst for the oxidative destruction of many toxic chemicals. In a sense, it anticipates the action of the protective enzymes of the intestinal wall and the liver."

A catalyst to toxin destruction...I wonder why charcoal in particular would do that. A provider of carbon for a chemical reaction? Wikipedia on charcoal:
Carbon source[edit]
Charcoal may be used as a source of carbon in chemical reactions. One example of this is the production of carbon disulphide through the reaction of sulfur vapors with hot charcoal. In that case the wood should be charred at high temperature to reduce the residual amounts of hydrogen and oxygen that lead to side reactions.

I think Peat agrees as well that achieving fully sterile gut is not practical. Or maybe it is possible to achieve it but it will only last for several days before it gets invaded by bacteria again. That's probably why he does the gut sterilization only occasionally.
That being said, his recommendation of taking charcoal 2-3 times a week will come pretty close to keeping the gut germ-free most of the time.
 

narouz

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I know where you're coming from with this, haidut.
In practice, I've run into problems with it tho.
 

jyb

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haidut said:
I think Peat agrees as well that achieving fully sterile gut is not practical. Or maybe it is possible to achieve it but it will only last for several days before it gets invaded by bacteria again. That's probably why he does the gut sterilization only occasionally.
That being said, his recommendation of taking charcoal 2-3 times a week will come pretty close to keeping the gut germ-free most of the time.

Actually, isn't the point that the count is reduced by all these measures? It's not about being 100% or 0% sterile...but reduce the count, hypothetically the serotonin production being proportional to the number of bacteria. And here hypothetically taking charcoal regularly keeps a lower count.

haidut, you're saying taking charcoal 2-3 times a week keeps gut close to sterile? That seems powerful and surprising...
 
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haidut

haidut

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jyb said:
haidut said:
I think Peat agrees as well that achieving fully sterile gut is not practical. Or maybe it is possible to achieve it but it will only last for several days before it gets invaded by bacteria again. That's probably why he does the gut sterilization only occasionally.
That being said, his recommendation of taking charcoal 2-3 times a week will come pretty close to keeping the gut germ-free most of the time.

Actually, isn't the point that the count is reduced by all these measures? It's not about being 100% or 0% sterile...but reduce the count, hypothetically the serotonin production being proportional to the number of bacteria. And here hypothetically taking charcoal regularly keeps a lower count.

haidut, you're saying taking charcoal 2-3 times a week keeps gut close to sterile? That seems powerful and surprising...

Powerful - yes. Why surprising?
 

jyb

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haidut said:
Powerful - yes. Why surprising?

Because I read all the time that bacteria in the intestine has a huge weight, we have a lot whether it's mostly good or mostly bad bacteria. So the fact that it can be near eliminated by taking a few pills is surprising...
 
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haidut

haidut

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jyb said:
haidut said:
Powerful - yes. Why surprising?

Because I read all the time that bacteria in the intestine has a huge weight, we have a lot whether it's mostly good or mostly bad bacteria. So the fact that it can be near eliminated by taking a few pills is surprising...

I would not call 50g of charcoal a few pills. That's the amount usually required to flush the colon and absorb most/all of the living gunk in there. If you buy the Solgar charcoal it has 100 pills at 280mg each. If you ingest the entire bottle (something I have done as an experiment) you'd still be consuming only half of the required charcoal for significant bacterial elimination. And let me tell you - ingesting 100 pills (or 28g) of charcoal is not easy or pleasant. So, while the full gut flush with charcoal is possible it's probably not practical for most people. Peat's recommendations were to take about 14-15 pills 3 times a day to stop endotoxin. That I think is much more practical and based on symptoms I have noticed it seems to also lower serotonin big time.
 

narouz

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haidut said:
jyb said:
haidut said:
Powerful - yes. Why surprising?

Because I read all the time that bacteria in the intestine has a huge weight, we have a lot whether it's mostly good or mostly bad bacteria. So the fact that it can be near eliminated by taking a few pills is surprising...

I would not call 50g of charcoal a few pills. That's the amount usually required to flush the colon and absorb most/all of the living gunk in there. If you buy the Solgar charcoal it has 100 pills at 280mg each. If you ingest the entire bottle (something I have done as an experiment) you'd still be consuming only half of the required charcoal for significant bacterial elimination. And let me tell you - ingesting 100 pills (or 28g) of charcoal is not easy or pleasant. So, while the full gut flush with charcoal is possible it's probably not practical for most people. Peat's recommendations were to take about 14-15 pills 3 times a day to stop endotoxin. That I think is much more practical and based on symptoms I have noticed it seems to also lower serotonin big time.

I've done something like that
with Natures Way brand,
only half the bottle at a time.

It seemed to work well.
I really didn't measure temp/pulse as I took it at bedtime.
I have a positive remembrance of my 3 month era of doing charcoal.

But I have my doubts about it being a complete "flush."
The macro biome thing is maybe really just being discovered.
I tend to think it is more complicated than he seems to picture it.
Maybe not!
He does not delve into it very deeply.
I confess this in one area where I don't feel bound by Peat's take absolutely.
I keep to it, mostly.
 

tara

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Peat has said activated charcoal can be very helpful against endotoxin, and has recommended it for particular issues or for occasional use. But he has also voiced concerns about particle size and persorption, and said grated carrot is probably safer for regular use for most people.
I've drunk AC slurry quite a few times. I imagine this is easier (and cheaper) than swallowing dozens of tablets.
 

RPDiciple

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haidut said:
jyb said:
haidut said:
Powerful - yes. Why surprising?

Because I read all the time that bacteria in the intestine has a huge weight, we have a lot whether it's mostly good or mostly bad bacteria. So the fact that it can be near eliminated by taking a few pills is surprising...

I would not call 50g of charcoal a few pills. That's the amount usually required to flush the colon and absorb most/all of the living gunk in there. If you buy the Solgar charcoal it has 100 pills at 280mg each. If you ingest the entire bottle (something I have done as an experiment) you'd still be consuming only half of the required charcoal for significant bacterial elimination. And let me tell you - ingesting 100 pills (or 28g) of charcoal is not easy or pleasant. So, while the full gut flush with charcoal is possible it's probably not practical for most people. Peat's recommendations were to take about 14-15 pills 3 times a day to stop endotoxin. That I think is much more practical and based on symptoms I have noticed it seems to also lower serotonin big time.

Do you get constipated or slower bowels from AC? i took 20 580mg capsules today and it made my bowels alot slower. Im gonna take another 20 before going to bed to see if it helps flushing out ***t
 
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haidut

haidut

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RPDiciple said:
haidut said:
jyb said:
haidut said:
Powerful - yes. Why surprising?

Because I read all the time that bacteria in the intestine has a huge weight, we have a lot whether it's mostly good or mostly bad bacteria. So the fact that it can be near eliminated by taking a few pills is surprising...

I would not call 50g of charcoal a few pills. That's the amount usually required to flush the colon and absorb most/all of the living gunk in there. If you buy the Solgar charcoal it has 100 pills at 280mg each. If you ingest the entire bottle (something I have done as an experiment) you'd still be consuming only half of the required charcoal for significant bacterial elimination. And let me tell you - ingesting 100 pills (or 28g) of charcoal is not easy or pleasant. So, while the full gut flush with charcoal is possible it's probably not practical for most people. Peat's recommendations were to take about 14-15 pills 3 times a day to stop endotoxin. That I think is much more practical and based on symptoms I have noticed it seems to also lower serotonin big time.

Do you get constipated or slower bowels from AC? i took 20 580mg capsules today and it made my bowels alot slower. Im gonna take another 20 before going to bed to see if it helps flushing out s***

Some people get constipation from AC, I usually don't. However, if already constipated AC can definitely make it worse. With lower doses (5-10 capsules) you should not be seeing much effect on bowel regularity.
 

natedawggh

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Taking supplemental lysine would have a similar effect right? By suppressing serotonin? I noticed when I took it that I didn't absorb much water from my digestion, which would be a sign of low serotonin.
 
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haidut

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OK, here is a follow up on the study above, which I read carefully. Couple of VERY interesting facts and observations.

1. Serotonin depletion can be achieved by administering an antibiotic mixture for only 14 days.
"...To assess the reversibility of microbial effects on host 5-HT metabolism, we depleted the gut microbiota in SPF mice via bi-daily antibiotic treatment beginning on P0, P21, or P42 and until P56. Treatment of P42 SPF mice with a cocktail of ampicillin, vancomycin, neomycin, and metronidazole (Reikvam et al., 2011) sufficiently recapitulates GF-associated deficits in serum and colon 5-HT and alterations in host colonic TPH1 and SLC6A4 expression (Figures 1 and 2). Interestingly, P0 and P21 antibiotic treatment also induces GF-related deficits in colonic 5-HT, but the effects on serum 5-HT are more pronounced when administered at P42, compared to P0 and P21 (Figure 1), suggesting potential confounding effects of early life or prolonged antibiotic treatment on microbiota-mediated modulation of peripheral 5-HT."

The study that discussed the microbiota depletion is this (and I will post a separate thread with it):

http://journals.plos.org/plosone/articl ... ne.0017996

"...Previously published protocols for depleting mice of their intestinal microbiota by administering broad-spectrum antibiotics in drinking water were difficult to reproduce. We show that twice daily delivery of antibiotics by gavage depleted mice of their cultivable fecal microbiota and reduced the fecal bacterial DNA load by 400 fold while ensuring the animals' health. Mice subjected to the protocol for 17 days displayed enlarged ceca, reduced Peyer's patches and small spleens. Antibiotic treatment significantly reduced the expression of antimicrobial factors to a level similar to that of germ-free mice and altered the expression of 517 genes in total in the colonic epithelium. Genes involved in cell cycle were significantly altered concomitant with reduced epithelial proliferative activity in situ assessed by Ki-67 expression, suggesting that commensal microbiota drives cellular proliferation in colonic epithelium."

As you can see, the antibiotic treatment was not only harmless but actually improved animal's immune health evidenced by their smaller spleen. This was likely due to the depleted 5-HT even though the authors probably did not know of the effects at that time. The antibiotic protocol was as follows:
"...To ensure a safe and stable delivery of the antibiotic concoction to every mouse subjected to the protocol we administered it by gavage every 12 hours. Due to occasional overgrowth of Candida spp. in pilot experiments (data not shown), we initiated our protocol with 3 days treatment of gavaging the antifungal substance amphotericin-B (1 mg/kg bodyweight (BW)) attempting to suppress fungal growth prior to starting the antibacterial treatment (Figure 2A). From day 3, ampicillin 1 mg/ml was added to drinking water and mice were gavaged every 12 hours with the antibiotic concoction consisting of vancomycin 50 mg/kg BW, neomycin 100 mg/kg BW, metronidazol 100 mg/kg BW, and amphotericin-B 1 mg/kg BW."
As you can see, antibiotic treatment produced fungal overgrowth (Candida) and an anti-fungal treatment had to be added. Given the doses used in mice, the human doses are: ampicillin 18mg/kg, vancomycin 3.6mg/kg, neomycin 7.2mg/kg, metronidazol 7.2mg/kg, amphotericin 0.07mg/kg.
As per the study, the full effects were observable by day 13 and there was no significant difference between day 13 and day 24 in terms of bacterial load in the feces.
So, for people willing to dramatically (and persistently) lower their endogenous 5-HT production, this may be a viable protocol. However, the serotonin study says that similar effects are achievable by ingesting pCPA at a human dose of 13mg/kg and it is likely less risky than completely killing off your microbiota.

2. The study discovered that specific bacterial metabolites also trigger 5-HT synthesis.
"...Of 16 metabolites examined, a-tocopherol, butyrate, cholate, deoxycholate, p-aminobenzoate (PABA), propionate, and tyramine elevate 5-HT in RIN14B chromaffin cell cultures (Figure 6D). Elevations in 5-HT correspond to increases in TPH1 expression from RIN14B cells (Figure 6E), suggesting that particular metabolites induced by Sp enhance 5-HT biosynthesis by ECs. We further tested for sufficiency to induce 5-HT in vivo. Notably, raising luminal concentrations of deoxycholate in colons of GF mice to levels seen in SPF mice (Sayin et al., 2013) sufficiently increases colon and serum 5-HT compared to vehicle-injected controls (Figures 6F and S6B). This restoration of peripheral 5-HT correlates with elevations in colonic TPH1 expression (Figure 6F). Increases in colon and serum 5-HT are also seen with injection of a-tocopherol, PABA and tyramine into colons of GF mice (Figures S6B and S6C). Consistent with in vitro RIN14B data, oleanolate has no statistically significant effect on elevating colon or serum 5-HT in GF mice (Figures S6B and S6C). Importantly, the effects of a single rectal injection of deoxycholate or a-tocopherol on raising colon 5-HT levels in GF mice are weak and transient, peaking within 1 hr of injection (Figure S6C). Consistent with this, there is no significant effect of acute colonic metabolite injection on GI transit time (Figure S6D), and there is only a trending improvement on platelet activation (Figure S6E)."
"..."...Consistent with our finding that the microbiota modulates colon and serum 5-HT via interactions with host colonic ECs, we find that particular fecal metabolites are similarly elevated by SPF, Sp, and hSp microbiota and sufficiently promote 5-HT in chromaffin cell cultures and in vivo (Figure 6; Table S1). Deoxycholate is a secondary bile acid, produced by microbial biotransformation of cholate. In addition to facilitating lipid absorption, it has endocrine, immunological, and antibiotic effects and is reported to modulate the microbiota (Islam et al., 2011) and the severity of Clostridium difficile and Camphylobacter jejuni infections (Buffie et al., 2014; Malik-Kale et al., 2008). Detrimental effects are also observed; deoxycholate exhibits carcinogenic properties and is linked to various cancers (Bernstein et al., 2011; Yoshimoto et al., 2013). Notably, deoxycholate is reported to promote GI motility by activating TGR5 G protein-coupled receptors on ECs (Alemi et al., 2013), which is consistent with our finding that Sp-induced metabolites raise 5-HT levels in ECs and that Sp colonization improves GI motility. Particular Clostridium species are known to possess high 7a-dehydroxylation activity required for the production of deoxycholate from cholate (Kitahara et al., 2001; Narushima et al., 2006), which is in line with our finding that Sp microbes, comprised largely of Clostridia, increase deoxycholate levels. Deoxycholate concentrations are substantially higher in the colon versus small intestine (Sayin et al., 2013), which, coupled to the finding that bacterial load and diversity is greater in the colon versus small intestine (Sekirov et al., 2010), could contribute to the regional specificity of microbiota-mediated increases in 5-HT synthesis to colonic ECs."

Some of those are well-known to the forum members. Peat has spoken against PABA and tyramine. However, the more surprising ones are tocopherol, butyrate and cholate. I guess the good news is that the effects of these metabolites were weak and transient. However, I do remember Peat saying butyrate has some strong pro-inflammatory effects and even though has much promise as a cancer or dementia treatment it has to be used sparingly. Alpha tocopherol is a surprising one (at least to me), so I wonder what Peat has to say about it. I guess if it does stimulate synthesis of serotonin in the gut, that would explain why some people on the forum have a consistent GI upset after ingesting larger doses of vitamin E.
Perhaps the most important finding here is cholate and deoxycholate, both of which are released by the liver/gallbladder to stimulate fat absorption. Since these metabolites transiently (but powerfully) stimulate serotonin synthesis, it may provide yet another explanation why Peat tries to steer away from fat, and why high fat diets are carcinogenic. I wonder if there is a study that compares the effects of different types of fat on cholate release. It would be a major win for Peat if PUFA stimulates a lot more cholate release than MUFA and saturated fat.


3. Some bacteria that can be used for colonizing the gut does NOT have stimulating effect on serotonin synthesis.
"...We demonstrate that indigenous spore-forming microbes from colons of SPF mice (Sp) and from a healthy human colon (hSp) sufficiently mediate microbiota effects on colonic and blood 5-HT. While we show that B. fragilis, B. uniformis, SFB, ASF, and a consortium of Bacteroides species cultured from mice, including B. thetaiotaomicron, B. acidifaciens, and B. vulgatus, have no effect on host peripheral 5-HT (Figure 3), whether other non-Sp microbial species or communities are capable of modulating colonic and serum 5-HT remains unclear."

So, people taking antibiotics for whatever reason can then attempt to re-colonize with these bacterial strains as a more permanent way of lowering their serotonin synthesis.

4. Gut serotonin is a major portion of total peripheral serotonin, and serotonin itself promotes the growth of certain pathogenic bacteria.
"...Our finding that colonic PCPA administration blocks the ability of the microbiota to promote colonic and blood 5-HT (Figures 3C and 3D) suggests that gut microbes require host Tph activity to upregulate peripheral 5-HT. Furthermore, SPF Tph1 KO mice lack >90% of intestinal and blood 5-HT levels (Savelieva et al., 2008), indicating that <10% of peripheral 5-HT is contributed directly by microbial synthesis or by Tph2-mediated biosynthesis in these mice. We find that the microbiota regulates relatively high levels of peripheral 5-HT, 64%of colonic (Figure 1), and 49% of serum concentrations (Figure 1) (Sjo¨ gren et al., 2012; Wikoff et al., 2009), further supporting the notion that the microbiota modulates 5-HT metabolism primarily by affecting host colonic ECs. Consistent with the understanding that ECs secrete low levels of 5-HT into the lumen, fecal concentrations of 5-HT are also significantly increased by the microbiota. Interestingly, 5-HT is reported to stimulate the growth of Enterococcus faecalis, E. coli, and Rhodospirillum rubrum in culture (Oleskin et al., 1998; Tsavkelova et al., 2006). In addition, 5-HT is a structural analog of auxins found in E. faecalis, R. rubrum, and Staphylococcus aureus, among other bacteria. Whether particular members of the microbiota alter host 5-HT biosynthesis to, in turn, support colonization, growth, or resilience of particular gut microbes is an interesting question for future study."


Overall, a very very interesting study and some specific practical ideas on how to lower peripheral serotonin with antibiotics or pCPA. I personally think that pCPA is the less risky option, but microbiota depletion has the advantage of being more long lasting as well as potentially having other beneficial effects on immune system (i.e. the smaller spleen seen in animals without microbiota).
Thoughts?
 
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