Hélène Chevallier, Clinical Methodologist at Biofortis Mérieux NutriSciences
How can our diet influence our health and especially our brain? Why can we talk about a gut-brain axis? Is the gut microbiota playing a role in this? These are some questions commonly addressed by the scientific community over the last few years.
This article follows our previous articles entitled “Microbiome involvement in satiety regulation » and “
Feeding the brain: exploring the gut-brain connection
». Here, we discuss one aspect of the gut brain axis: the link between consumption of tryptophan’s rich food, metabolism of the serotonin neurotransmitter in the gut, and the effect of this substance, especially on the brain.
When we talk about serotonin, first we think of the neurotransmitter, so we all see the link between the brain and this substance. However, we must not forget the major role of the gut in its biosynthesis. Indeed, about 90% of all serotonin synthesis is done by enterochromaffin cells in the gastrointestinal epithelium from the tryptophan amino acid (1). By the way, the first scientist who identified this substance (Vittorio Erspamer) called it ‘enteramine’. The location of its biosynthesis involved also mucosal mast cells and myenteric neurons (2). Yet, most research focused on the effect of this substance on the brain, this explains, at least partially, why the data on gastrointestinal function were only recently discovered. The concept of the gut-brain axis may have brought up the current interest for the gut function of serotonin. Serotonin produced in the gut is then transported in the blood by platelets.
Tryptophan is the precursor of peripherally- and centrally- produced serotonin, but it has been estimated that only 3% of dietary tryptophan is used for serotonin synthesis throughout the body and only 1% is used for serotonin synthesis in the brain. Indeed, tryptophan is involved: 1) in protein synthesis; 2) in synthesis of kynurenine, which further leads to the synthesis of nicotinic acids for example (3).
According to Palego et al., “only a very small amount of endogenous/dietary L-Trp (Ed: tryptophan) is converted into serotonin, suggesting that the bioavailability of this AA (Ed: aminoacid) and/or changes in the regulation of its metabolism in tissues might be critical for maintaining a healthy balance between all its different paths and destinies” (4).
The serotonin molecules produced in the intestine and the brain are structurally identical, they are simply located in different places and secreted by different cells, but their local effect can be different. Two different isoenzymes of tryptophan hydroxylase (Tph) are involved, Tph1 and Tph2 (2). In the brain, the biosynthesis of serotonin depends on the amount of tryptophan that enters through the blood-brain barrier. Only free plasma tryptophan (not bound to albumin) enters the brain. In addition, other amino acids compete with free tryptophan and limit its entry into the brain.
Furthermore, transformation of serotonin into melatonin can occur, primarily in the pineal gland or epiphysis.
Tryptophan => 5-hydroxytryptophan (5-HTP) => Serotonin (5-HT) => Melatonin
Yano et al, demonstrated that the microbiota plays a vital role in regulating serotonin in the host (2). They discovered that spore-forming bacteria promote serotonin biosynthesis by elevating Tph1 expression in colonic enterochromaffin cells, in the gut microbiota of mice and humans. Furthermore, they were able to “identify select microbial metabolites that confer the serotonergic effects of indigenous spore-forming microbes”. Among 16 metabolites examined, they found that “α-tocopherol, butyrate, cholate, deoxycholate, p-aminobenzoate (PABA), propionate, and tyramine elevate serotonin in RIN14B chromaffin cell cultures”.
Serotonin is involved in functions including sleep, mood-anxiety, cognition, control of appetite, and body temperature, acting as a paracrine factor, endocrine hormone, neurotransmitter, and growth factor (1,4,5). Others activities have been described, such as effects on immunity and inflammation (contributing to the severity of intestinal inflammation), differentiation of blood stem cells (leading to lower bone mass by inhibiting osteoblast proliferation), the hemodynamic function, endocrine hormone activity, and gut function (6). Regarding the gut function, serotonin released from enterochromaffin cell is involved in peristalsis, motility, vasodilation, and perception of pain or nausea (by activating signals sent to the central nervous system that stimulate digestive reflexes), through activation of a various serotonin receptors on intrinsic and extrinsic afferent nerve fibers that are located in the lamina propria (7).
The serotonin metabolic pathway illustrates the gut-brain axis well and how the diet can influence our health and brain. Tryptophan-rich foods are present in animal and vegetal products: e.g dairy products eggs (white), meat, seafood (fish and crustaceous), potatoes, chickpeas, soybeans, cocoa beans, and nuts (walnuts, hazelnuts, and cashew) (4). Tryptophan needs are covered by a diversified and balanced diet without any supplementation required.
The role of the microbiota on serotonin metabolism needs to be further explored and the biological effect of serotonin better understood.
1. Jenkins TA, Nguyen JCD, Polglaze KE, Bertrand PP. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients [Internet]. 2016 Jan 20 [cited 2019 Jan 8];8(1). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728667/
2. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, et al. Indigenous Bacteria from the Gut Microbiota Regulate Host Serotonin Biosynthesis. Cell. 2015 Apr 9;161(2):264–76.
3. Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009 Mar 23;2:45–60.
4. Palego L, Betti L, Rossi A, Giannaccini G. Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans. J Amino Acids [Internet]. 2016 [cited 2019 Jan 8];2016. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737446/
5. Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes. 2013 Feb;20(1):14–21.
6. Berger M, Gray JA, Roth BL. The Expanded Biology of Serotonin. Annu Rev Med. 2009;60:355–66.
7. Mawe GM, Hoffman JM. Serotonin Signaling in the Gastrointestinal Tract: Nat Rev Gastroenterol Hepatol. 2013 Aug;10(8):473–86.