Our microbiome produces serotonin (5-HT), independently of the GI tract
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The topic of endotoxin/LPS, 5-HT and gut dysbiosis is a recurring one in the bioenergetic sphere and there is hardly a chronic (and acute – i.e. flu, COVID-19) disease that has not been at least partially linked to our gut bacteria overproducing endotoxin, which then acts on the gut lining – enterochromaffin cells (EC) – to trigger 5-HT, histamine and nitric oxide (NO) production, leading to GI and subsequently systemic inflammation and diseases. As such, keeping the gut bacteria (microbiome) under control with antibiotics, insoluble fiber, charcoal, etc is one of the main mechanisms for improving health in the bioenergetic sphere. Another important aspect in the bionergetic view is that one should consume foods that are easily digestible so that they are absorbs easily and early in the GI tract (stomach and upper small intestine) and do not reach the colon where they would feed the microbiome. There is also a focus on not consuming substances that physically or chemically irritate the intestine (e.g. silica, talc, titanium dioxide, gums, vegetable rennet, etc) since irritation (even without presence of food) would also trigger the same serotonin-histamine-NO-inflammation cascade.
Well, the study below demonstrates why keeping the microbiome in check may be a top priority. It shows that human gut bacteria, at least in babies, produces very high amounts of 5-HT independently of the EC in the gut. In fact, about half of the bacterial species contained in the microbiome (both animal and human) apparently produce 5-HT on their own. That bacterial-derived 5-HT has the role of an immunosuppressant for the baby to dampen allergic reactions. Aside from elucidating an additional major source of 5-HT int the human organism, the study also suggests that “exogenous” serotonin is also bioactive, which is something most doctors still refuse to believe. Namely, medicine has focused mostly on the 5-HT produced by the EC in the gut since they claim that mostly such 5-HT enters the circulation and is of systemic importance. Since the externally (bacterially) produced 5-HT in this study most certainly produced systemic (immune) effects, I think it is pretty clear that exogenous 5-HT matters. That corroborates Ray’s views that one should be careful when consuming foods naturally high in 5-HT such as kiwis, dates, and (unripe) bananas.
https://www.science.org/doi/10.1126/sciimmunol.adj4775
https://www.the-scientist.com/gut-serotonin-curbs-the-developing-immune-system-72265
“…The infant gut is packed with a medley of molecules that dictate development during a critical time in a newborns’ life. But how these molecules interact with and influence immune cells early in life isn’t fully understood. Now, in a study published in Science Signaling, a team of scientists revealed how one molecule produced in the gut, the neurotransmitter serotonin, activates a subset of T cells and dampens the immune system.1 The authors linked gut-derived serotonin to the creation of tolerance against allergens, suggesting that the pathway may play a role in the development of conditions such as asthma and food allergies.”
“…However, when Zeng and her team profiled the metabolites in the gut of neonatal mice, they found that the neonatal intestine had an unexpectedly high amount of the neurotransmitter serotonin. But the serotonin was not coming from the enterochromaffin cells, the cells that produce serotonin in adults, but rather from the gut’s resident bacteria. When they isolated bacteria from both neonatal mice and healthy human infants they found that around half of the microbes in their samples produced serotonin.”
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Incredibly interesting study, thanks Haidut.
This does have some interesting implications regarding serotonin though. Could serotonin possibly be preventative in autoimmune conditions? I mean if they are correct that it dampens immune/allergenic responses. Obviously, I'm not advocating that people should seek to increase it, nor am I saying the benefits of that function would outweigh the harm.
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@RandomUser An experience with crohns tells me, it is precisely the imbalance (fast reduction of) serotonin, that triggers inflammtion. I am not saying serotonin is good. However, in the context of balance with dopamine, I think there needs to be some as a mediator and suppressor of hyper reactions (such as crohns!). If we think about it, inflammation is widespread, in many people, but for sure not everybody has the crohns type, more acutely threatening. This must be another paradigm then. I believe this what Dr. Lechin was onto, fixing these neurotransmitters gross imbalances to restore function, regardless of "normal" type inflammation. The U.S. pretty much drove him out of the country btw.
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@bio3nergetic
Dietary supplementation of thiamine enhances colonic integrity and modulates mucosal inflammation injury in goats challenged by lipopolysaccharide and low pH"In the current ruminant production systems, large amounts of high-concentrate (HC) diets are fed to goats or dairy cows to maximise the yield of meats and milk(Reference Kennelly, Robinson and Khorasani1). Although these short-term feeding regimens might be effective to support energy requirements, the excessive amounts of non-structural fermentable carbohydrates lead to a lot of negative influences as the accumulation of SCFA and microbial translocation in rumen and hindgut(Reference Gaebel, Bell and Martens2,Reference Plaizier, Krause and Gozho3) . Moreover, **the decline of pH in the rumen and gastrointestinal tract likely results in the lysis of gram-negative bacteria and the release of lipopolysaccharide (LPS) that translocate into the blood circulation system, which enhances mucosal damage of the hindgut(Reference Khafipour, Krause and Plaizier4). Under normal physiological conditions, only a small amount of LPS penetrates the gastrointestinal epithelial barrier by a special immune mechanism as a consequence of an endocytotic pathway(**Reference Andersen, Hesselholt and Jarlov5,Reference Drewe, Beglinger and Fricker6) . In contrast, under physiological stresses caused by endotoxin and cytokines, the barrier properties of tight junctions (TJ) can be provoked, causing increased epithelial permeability and shift of LPS(Reference Gareau, Silva and Perdue7)."
also: https://www.objectivenutrients.com/insights/when-sibo-ibs-constipation-are-unrecognized/
"The gastrointestinal tract is one of the main systems that can be affected by a deficiency of thiamine (vitamin B1). Clinically, a severe deficiency in this nutrient can produce a condition called “Gastrointestinal Beriberi”, which in my experience is massively underdiagnosed and often mistaken for SIBO or IBS-C"
"The GI tract possesses its own individual enteric nervous system (ENS), often referred to as the "second brain". Although the ENS can perform its job somewhat autonomously, inputs from both the sympathetic and parasympathetic branches of the autonomic nervous system serve to modulate gastrointestinal functions. The upper digestive organs are mainly innervated by the vagus nerve, which exerts a stimulatory effect on digestive secretions, motility, and other functions. Vagal innervation is necessary for dampening inflammatory responses in the gut and maintaining gut barrier integrity [1]"Thiamine and fatigue in inflammatory bowel diseases: an open-label pilot study
"Objectives: To demonstrate that fatigue and other disorders related to ulcerative colitis and Crohn's disease are the manifestation of an intracellular mild thiamine deficiency and not due to malabsorbtion, augmented requirements, or nutritional factors, and that this dysfunction is curable with high doses of thiamine administered orally or parenterally. "https://www.objectivenutrients.com/insights/leaky-gut-syndrome-causes-symptoms-and-solutions-for-gut-healing/
Please read this article.TKT maintains intestinal ATP production and inhibits apoptosis-induced colitis
"Inflammatory bowel disease (IBD) has a close association with transketolase (TKT) that links glycolysis and the pentose phosphate pathway (PPP). However, how TKT functions in the intestinal epithelium remains to be elucidated. To address this question, we specifically delete TKT in intestinal epithelial cells (IECs). IEC TKT-deficient mice are growth retarded and suffer from spontaneous colitis. TKT ablation brings about striking alterations of the intestine, including extensive mucosal erosion, aberrant tight junctions, impaired barrier function, and increased inflammatory cell infiltration. Mechanistically, TKT deficiency significantly accumulates PPP metabolites and decreases glycolytic metabolites, thereby reducing ATP production, which results in excessive apoptosis and defective intestinal barrier. Therefore, our data demonstrate that TKT serves as an essential guardian of intestinal integrity and barrier function as well as a potential therapeutic target for intestinal disorders.""The TKT activity is dependent on thiamine, and thiamine deficiency has a strong association with IBD [19]. Moreover, erythrocyte TKT activity is declined in patients suffering from IBD [20]. Furthermore, lack of transketolase-like 1 (TKTL1), which belongs to the TKT gene family, aggravates murine experimental colitis [21]. "
I suffered for many years with IBS, Leaky Gut, SIBO, multiple food sensitivities, low stomach acid, very poor esophageal peristalsis, strong gluten sensitivity . I'm well now. High dose thiamine hcl resolved all of my digestive tract problems. My gut bacteria normalized too. On their own. I also take other b vitamins (niacinamide, riboflavin, biotin, a little b6, some b5) and I take 3.5 grams of magnesium glycinate, divided into 2 doses daily. I followed Dr. Costantini's protocol to determine my optimum dose of oral thiamine hcl. I've been taking 1 gram of thiamine hcl, twice daily for 4 years now and I continue to have excellent health. If your gut is really a mess, you might need thiamine hcl injections for a while first.
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@mostlylurking Thanks for the post. Yes, B1 was also part of my arsenal as well other B's and other substances, including Progesterone. My life is different now, the digestive thing isnt really a problem any more, save for occasional issue due to something eaten and/or however their butchery surgery from 24 years ago affects me. And that is thanks to finding Peat a little over 10 years ago and changing so many things about how I eat, how I view things and the nuances in between.
My previous post was to reflect on my thinking on serotonin and that it is different slightly, because prior to Peat, my research forced me to see things through slightly different lens. And long story short, I really don't believe talking about "serotonin" without making distinctions between cellular and plasma, and the varying receptors, gut versus brain AND in which certain parts of the brain, as well as the relationship to dopamine, MAO activity, etc., can give us an accurate picture. There is something more. Which is why people like Lechin was helping patients with inflammation and even cancer (probably why he got chased out of the country). but with a slightly different angle. The general ideas on serotonin and inflammation, slowed metabolism, fibrosis, torpor, stimulating cortisol, I think are correct, until the nuances matter. Then, there needs to be an adjustment to the approach. If I was smarter, I would have figured this puzzle out long ago. But I have figured out how to maneuver with this condition, again thanks to Peat and all things and thinking Peat. The ultimate illumination and control however is still to be discovered.
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@haidut I suspect that 5-HT is high in babies because constipation/impaction of the gut would be life threatening for a baby. 5-HT keeps things moving along in the intestine; it increases/intensifies peristalsis.
Serotonin Deficiency Is Associated With Delayed Gastric EmptyingI suspect that the issue of serotonin (5-HT) getting through the intestinal wall and into the blood stream is the primary concern; so long as the 5-HT remains inside the intestine (along with the endotoxin) things should be fine. If the integrity of the intestinal wall is compromised and endotoxin and 5-HT are able to seep through into the blood stream major problems happen (sepsis, high serotonin symptoms).
The health of the epithelial cells that line the intestine are important because if they fail, leaky gut happens. Thiamine is believed to be important for the epithelial cell function. See here: Dietary supplementation of thiamine enhances colonic integrity and modulates mucosal inflammation injury in goats challenged by lipopolysaccharide and low pH "The results show that dietary thiamine supplementation could improve the colon epithelial barrier function and alleviate mucosal inflammation injury in goats after lipopolysaccharide and low pH challenge."
Another important body part that requires excellent epithelial cell function is the blood/brain barrier. Thiamine deficiency compromises the blood/brain barrier too.
Thanks for all you do! I always appreciate your posts.