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, serotonin 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.


Find out more about the gut-brain axis from the article, Stress and the gut microbiome.


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 (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 motility.1


Gut bacteria can influence serotonin production in the gut

EC cells are sensory cells and when stimulated, they 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 (SCFAs), 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 (Fig. 2).

EC cells secrete serotonin into the lamina propria (the thin layer of connective tissue lining the gut epithelium), as well as into the lumen1. Here, serotonin 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. 20209, 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. 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 it is this serotonin that in turn, suppresses the expression of virulence genes by pathogens. These genes influence whether a 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 which means the body cannot synthesise tryptophan on its own and therefore, it must be obtained through 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), vitamin B3 (niacin), and glutathione (an antioxidant predominantly produced by the body11). Common foods that contain vitamins B6 and B3 can be seen in the table below (Fig. 3).

Increasing the consumption of fermentable prebiotic fibres commonly found in an array of plant foods will support the growth of specialised microbial species in the gut. These species can increase SCFA production which will ultimately help stimulate EC cells and thereby support serotonin production.


Fig 3. 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 various neurological and cognitive functions, as well as many physiological processes, but 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 from across all five food groups can help support the body in producing adequate serotonin levels.


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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.


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