Serotonin Production In The Gut Is Fully Controlled By Microbiome

[haidut]

A year and a half ago I posted about a study which found that serotonin production in the gut depends on the bacteria living in the colon.
Serotonin Production (gut) Depends On Bacteria
At the time, the study was considered controversial as the role of microbiome in serotonin production was thought to be relatively minor. However, now another study points the finger at the bacteria in the colon as the main regulators of serotonin production through the receptor TLR2.
TLR2 - Wikipedia
The TLR2 receptor is related to the infamous TLR4 (which is the main endotoxin "receptor") but unlike TLR4, the TLR2 gets activated by the mere presence of bacteria in the colon. Thus, any amount of bacteria in the colon will act as agonist at that receptor, and the study below found that TLR2 agonism inhibits the serotonin transporter, which is responsible for the disposal if serotonin. Thus, TLR2 activation results in an effect similar to what the SSRI drugs do in the brain, and these higher gut serotonin levels have been linked to everything from IBD to neurodegenerative disease and even cancer.
Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation
Serotonin Availability Altered By Gut Microbiota Recognition Receptor
http://medicalxpress.com/news/2016-12-gut-microorganisms-affect-physiology.html

"...The finding, published in PLOS ONE, comes as scientists across the world are working to understand the complicated interactions between the "invisible world" of the microbiota in our bodies and the impact they have on our health and even our moods. Recently, scientists in California found evidence that the bacteria in the gut play a role in causing Parkinson's Disease. It may also help explain how the microbiota in our guts affect our physiology. Inflammatory bowel disease is thought to be triggered when TLR2 is not functioning properly, but so far, the mechanisms behind this have not been fully understood. This study aimed to further this understanding, and was supported the Foundation for the Study of Inflammatory Bowel Diseases in Aragón (ARAINF), in Spain. Dr Eva Latorre, a postdoctoral researcher at the University of Exeter Medical School, said the new finding helped to further understanding in a fast-growing research area. She said: "This paper has concluded that the protein TLR2 alters the availability of serotonin, which is important in a range of conditions from depression to inflammatory bowel disease. It is early days in this research though. We need to understand much more about the relationship between the microbiota in our guts and how they interact, before we can hope to harness effective new treatments." The research team examined human cells in a model of the intestine in the laboratory, looking at how they express proteins and RNA - activities which regulate how they behave. They found that TLR2 controls serotonin transporter - obtaining the same result in studies on mice. Principal investigator of this study, Professor José E Mesonero, at the University of Zaragoza, said: "This paper opens our minds about the complex universe of this forgotten organ: the microbiome. We have concluded that TLR2 not only can detect microbiota, but also modulate serotonin transport, one of the crucial mechanism in neurological and inflammatory diseases. Much has to be yet studied, but this work can improve our understanding about the connection between gut and brain thought microbiota.""

 

[Bahaa El wazzan]

Watching

 

[amethyst]

Very interesting study. Stress can affect the bacteria level in your colon. So maybe the higher the stress, the higher the bacteria, the higher the serotonin leading to conditions like IBS?

 

[Mito]

Do TLR4 antagonists antagonize TLR2 receptors also?

 

[yerrag]

I am disposed to see bacteria like I see Popeye and Brutus-good and bad. If the good bacteria is dominant, am I right to assume a correlation to low serotonin levels, and conversely, bad bacteria to high serotonin levels? Perhaps there is really no good or bad bacteria, but a microbiome where there is a healthy balance of microorganisms, with this balance contributing to lower serotonin levels. In the case of candidaiasis, where there is an unhealthy excess of candida albicans in the microbiome, wouldn't there be high serotonin levels? And when we take probiotics after an antibiotic regimen, to reestablish the balance in the biome, can we expect serotonin to go down to healthy levels as well?

 

[Wagner83]

There's a askyourherbdoctor podcast with Ray in which microbiome is mentioned. It makes sense and I think Ray sees all the digestive system as a whole, I wonder if that reinforces the idea that hemorrhoids are a sure sign of important inflammation and serotonin production (and NO).


As for what is good and bad bacteria, good luck on that topic :)

 

[amethyst]

I am disposed to see bacteria like I see Popeye and Brutus-good and bad. If the good bacteria is dominant, am I right to assume a correlation to low serotonin levels, and conversely, bad bacteria to high serotonin levels? Perhaps there is really no good or bad bacteria, but a microbiome where there is a healthy balance of microorganisms, with this balance contributing to lower serotonin levels. In the case of candidaiasis, where there is an unhealthy excess of candida albicans in the microbiome, wouldn't there be high serotonin levels? And when we take probiotics after an antibiotic regimen, to reestablish the balance in the biome, can we expect serotonin to go down to healthy levels as well?

Good questions. I would like to know this as well.- does a dominance of bad bacteria lead to too high serotonin in the gut? I would say yes, if one is having symptoms, ie: irritable bowel syndrome, bloating, SIBO, digestive issues etc.

 

[haidut]

Very interesting study. Stress can affect the bacteria level in your colon. So maybe the higher the stress, the higher the bacteria, the higher the serotonin leading to conditions like IBS?

Yep, Ray said something along those lines in a few interviews and studies have since confirmed it. Anti-serotonin drugs can probably cure IBS and a few TPH inhbitors are in latest stages of clinical trials for IBS and are being cautiously called "curative".

 

[haidut]

Do TLR4 antagonists antagonize TLR2 receptors also?

Some of them do. I think amitriptyline and ketotifen may be the best options to block TLR2 receptors.
Evidence that tricyclic small molecules may possess Toll-like receptor and MD-2 activity
Mast Cells Play a Crucial Role in Staphylococcus aureus Peptidoglycan-Induced Diarrhea

 

[Peater Piper]

This link claims serotonin production occurs in the gut even in germ-free mice, though at a reduced rate:
Microbes Help Produce Serotonin in Gut | Caltech

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.

 

[haidut]

This link claims serotonin production occurs in the gut even in germ-free mice, though at a reduced rate:
Microbes Help Produce Serotonin in Gut | Caltech

I suppose it comes down to how well the microbiome was depleted. Some studies just give antibiotics and assume the flora was killed. The older study I posted more than a year ago I think took samples from the colon tissue to make sure there is no bacteria. In those germ-free mice the serotonin production fell by more than 90%.

 

[jyb]

I suppose it comes down to how well the microbiome was depleted. Some studies just give antibiotics and assume the flora was killed. The older study I posted more than a year ago I think took samples from the colon tissue to make sure there is no bacteria. In those germ-free mice the serotonin production fell by more than 90%.

If gut serotonin is 100% controlled by germs and if you're germ free, how do you digest? Given serotonin's function in bowel movement (cf the blocked gut side effect of Ondansetron). Theoretically speaking.

 

[haidut]

If gut serotonin is 100% controlled by germs and if you're germ free, how do you digest? Given serotonin's function in bowel movement (cf the blocked gut side effect of Ondansetron). Theoretically speaking.

Stretching the intestine by just walking briskly or even a 10sec jog will produce serotonin. Bacteria are the main factor at rest but mechanical stimulation will also make gut cells produce serotonin. Peristalsis is not driven only by serotonin. Serotonin's role is simply to signal a toxic event and thus "urge" bowel emptying. You can digest fine with even 1% of the baseline serotonin in people with gut flora.

 

[raypeatclips]

Stretching the intestine by just walking briskly or even a 10sec jog will produce serotonin.

Do you think stretches like yoga stretches like "the crab" would stretch the intestine and produce serotonin?

 

[haidut]

Do you think stretches like yoga stretches like "the crab" would stretch the intestine and produce serotonin?

Possibly yes. I guess it depends on how long the position is held for. A good indication of how much serotonin a specific activity generates is if you have to go to the bathroom after activity. Running is notorious for giving people "the shits" even mid-run, and definitely after that. I know some people who get the same effects from yoga but don't know much about it to generalize.

 

[lollipop]

Possibly yes. I guess it depends on how long the position is held for. A good indication of how much serotonin a specific activity generates is if you have to go to the bathroom after activity. Running is notorious for giving people "the shits" even mid-run, and definitely after that. I know some people who get the same effects from yoga but don't know much about it to generalize.

Interesting. I have experienced needing to go in the middle of practicing yoga.

 

[raypeatclips]

Interesting. I have experienced needing to go in the middle of practicing yoga.

I bet many perceive this in a positive way, a form of "detox."

 

[lollipop]

I bet many perceive this in a positive way, a form of "detox."

Right?!?! OR even healthy "peristaltic action".

 

[Wagner83]

As far as yoga is concerned I can see how from a pure mechanical point of view it would help hurry digestion.

 

[Peater Piper]

I suppose it comes down to how well the microbiome was depleted. Some studies just give antibiotics and assume the flora was killed. The older study I posted more than a year ago I think took samples from the colon tissue to make sure there is no bacteria. In those germ-free mice the serotonin production fell by more than 90%.

That makes sense, and I've wondered how they know at what point the mice are "sterile." Perhaps they never are completely bacteria free. Do you think serotonin release from strenuous endurance training is the cause of increased intestinal permeability from said exercise?