Serotonin – More than just a mood regulator

Author: Christine Stewart

14 August 2020

 

 

Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter well known for its ability to promote feelings of happiness and wellbeing – however it can also play significant roles within the gastrointestinal tract, pancreas, liver and bones1,2.

The vast majority of the body’s serotonin (approx. 90%) is produced and stored in the gut by enterochromaffin (EC) cells located in the gastrointestinal epithelial layer3,4 with the second major pool of serotonin produced in the brain (approx. 5%)5. Interestingly, serotonin cannot cross the blood-brain barrier and thus the role serotonin plays in the body is somewhat different to the role it plays in the brain5.

 

Differing roles of serotonin

Serotonin produced in the brain acts as a neurotransmitter and is responsible for learning, behaviour, mood and appetite4.  Whereas peripherally produced serotonin acts more like a hormone and regulates a plethora of physiological functions such as glucose and lipid homeostasis, intestinal inflammatory processes, and gut motility2,5 (See Fig. 1). The reason why serotonin can exert its actions throughout the body is largely due to the 14 different receptor types it can activate5.

Fig.1 Gut bacteria and their metabolites in the production of serotonin and its role in gut motility1.

Interested in knowing more about how stress interacts with your microbiome?  Read the blog.


Gut bacteria can influence serotonin production in the gut

EC cells are sensory cells and when stimulated – produce serotonin from the breakdown of tryptophan via the enzyme tryptophan hydroxylase (TpH1)1,6. Several species of gut bacteria have the ability to produce the short chain fatty acids (SCFA) butyrate and propionate – which can bind to free fatty acid receptors on EC cells to stimulate the production of TpH1 and serotonin2,7 (Fig 2). Gut bacteria can also produce secondary bile acids which can trigger the release of serotonin from EC cells through activation of the G-coupled-protein bile acid receptors2(See Fig. 2).

Serotonin is secreted by EC cells into the lamina propria (the thin layer of connective tissue lining the gut epithelium) as well as into the lumen1 where it helps to regulate sensory, motor and secretory functions through interacting with different serotonin receptor subtypes8.

Fig. 2 Synthesis of serotonin from SCFA’s and secondary bile acids stimulating receptors on EC cells2.

 

How serotonin may impact gut bacteria – specifically pathogens

Interestingly, a recent paper detailing a mouse study by Kumar et al. 2020, highlights yet another potential purpose for serotonin. The paper found that serotonin could decrease the gene expression of certain virulence factors produced by pathogenic species such as Escherichia coli. Specifically, serotonin suppressed the gene expression for the LEE pathogenicity island – which activates the mechanism used by some pathogens to inject their virulence factors into the host cells. Essentially, this means serotonin blocks pathogens from invading colon tissue and causing infection. The amount of pathogen gene suppression that occurred in this study was also relative to the amount of serotonin present – i.e. when serotonin levels were decreased in the gut, there was an increased chance the pathogen would infect, whereas when serotonin levels increased, the pathogen’s potential to invade cells was reduced.

The authors also demonstrated that gut bacteria can directly influence serotonin production in the colon lumen. They showed this by measuring the amount of serotonin present in the lumen and in the colon tissue of mice treated with antibiotics, compared to serotonin levels in a control group with an intact gut microbiome. They found serotonin levels were reduced in the lumen but not in the colon tissue in the mice treated with antibiotics compared to control mice. This indicates that the gut microbiota can indeed impact serotonin levels in the lumen.

In summary, this paper presents a novel mechanism whereby the gut microbiota promotes serotonin production in the colon lumen, and this serotonin in turn suppresses the expression of virulence genes by pathogens, influencing whether the pathogen will be able to invade and cause illness9.  

 

How diet can support serotonin production

Tryptophan is the only precursor for both centrally and peripherally made serotonin10. It is one of the nine essential amino acids – meaning the body cannot synthesise tryptophan on its own and it must be obtained through the diet. Oats, bananas, milk, tuna, cheese, bread, poultry and peanuts are common foods that contain tryptophan.

Serotonin synthesis from tryptophan also requires nutrients such as vitamin B6 (pyridoxine) and vitamin B3 (niacin) plus glutathione (an antioxidant predominantly produced by the body[11) . Common foods that contain vitamin B6 and niacin can be seen in the table below.

 

Increasing consumption of fermentable prebiotic fibres commonly found in an array of plant foods will support the growth of specialised species and ultimately increase the production of SCFA’s which will help to support the production of serotonin by stimulating EC cells.

Table 1. Foods and associated nutrients that may support serotonin synthesis

 

Serotonin in summary

Serotonin plays many roles in the human body. Not only can serotonin influence our mood and learning, and various physiological processes including gut motility, recent research shows its presence in the gut lumen may also reduce the ability for opportunistic pathogens to invade. Many common foods contain the nutrients to support serotonin production both in the central nervous system and peripherally in the gut. Consuming a wide variety of foods in our diet from across all five food groups can help support the body in producing adequate serotonin levels.

 


About the Author

Christine Stewart

Christine is a Nutritionist and Registered Nurse and works as a Clinical Application Specialist at Microba. Christine has a passion for obesity-related chronic disease prevention and furthering our understanding of the association between the microbiome and metabolic disease.

References

1. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY (April 2015). “Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis”Cell161 (2): 264–76. doi:10.1016/j.cell.2015.02.047PMC 4393509PMID 25860609.
2. Martin AM, Young RL, Leong L, Rogers GB, Spencer NJ, Jessup CF, Keating DJ. The Diverse Metabolic Roles of Peripheral Serotonin, Endocrinology, 2017; Volume 158, Issue 5, Pages 1049–1063, https://doi.org/10.1210/en.2016-1839.
3. Bertrand, Paul P.; Bertrand, Rebecca L. (2010). “Serotonin release and uptake in the gastrointestinal tract”Autonomic Neuroscience153 (1–2): 47–57. doi:10.1016/j.autneu.2009.08.002PMID 19729349.
4. Jenkins TA, Nguyen JC, Polglaze KE, Bertrand PP. Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis. Nutrients. 2016;8(1):56. Published 2016 Jan 20. doi:10.3390/nu8010056.
5. El-Merahbi R, Löffler M, Mayer A, Sumara G. The roles of peripheral serotonin in metabolic homeostasis. FEBS Lett. 2015;589(15):1728-1734. doi:10.1016/j.febslet.2015.05.054.
6. McKinney, J., Knappskog, P.M. and Haavik, J. (2005), Different properties of the central and peripheral forms of human tryptophan hydroxylase. Journal of Neurochemistry, 92: 311-320. doi:10.1111/j.1471-4159.2004.02850.x.
7. Fukumoto S, Tatewaki M, Yamada T, et al. Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol. 2003;284(5):R1269-R1276. doi:10.1152/ajpregu.00442.2002.
8. Stasi C, Bellini M, Bassotti G, Blandizzi C, Milani S. Serotonin receptors and their role in the pathophysiology and therapy of irritable bowel syndrome. Tech Coloproctol. 2014;18(7):613-621. doi:10.1007/s10151-013-1106-8.
9. Kumar A, Russell RM, Pifer R, Menezes-Garcia Z, Cuesta S, Narayanan S, MacMillan JB, Sperandio V. The serotonin neurotransmitter modulates virulence of enteric pathogens. Cell Host & Microbe. 2020;28:1-13. doi:10.1016/j.chom.2020.05.004.
10. 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;2:45-60. doi:10.4137/ijtr.s2129.
11. National Center for Biotechnology Information. PubChem Compound Summary for CID 6305, Tryptophan. https://pubchem.ncbi.nlm.nih.gov/compound/Tryptophan. Accessed Aug. 5, 2020.