Scientists have long known that most of the body’s serotonin—a neurotransmitter that helps regulate mood, digestion, and other functions—comes from the gut. Now, a new study shows that specific strains of gut bacteria can produce serotonin in the gut, where it promotes nerve growth and regulates intestinal motility. 

The findings, published in Cell Reports, suggest that targeting serotonin-producing bacteria could be a strategy to improve digestive health.

Gut microbes are known to influence serotonin production indirectly, but until now, it was unclear whether specific bacteria could produce serotonin in the gut and affect intestinal nerve growth and function.

Chiara Moretti at the University of Gothenburg in Sweden and her colleagues set out to address this question by focusing on two bacteria, Limosilactobacillus mucosae and Ligilactobacillus ruminis, that have been consistently found in human gut samples.

Producing serotonin

When germ-free mice genetically engineered to lack the enzyme needed to make serotonin were colonized with a bacterial mix containing L. mucosae and L. ruminis, serotonin levels in the gut increased, but blood levels remained unchanged. This finding indicates that the bacteria mainly influence gut serotonin rather than circulating serotonin. 

The colonized mice also showed improved nerve density in the gut and faster transit times, suggesting that microbial serotonin directly affects gut function.

In cells grown in a lab dish, the bacterial mix converted a serotonin precursor into serotonin. However, L. mucosae or L. ruminis strains alone could not produce serotonin, the researchers found. The team also identified an enzyme in L. mucosae that helps produce serotonin, revealing a molecular mechanism behind microbial serotonin production.

Gut function

Next, the researchers found that people with irritable bowel syndrome have lower levels of L. mucosae, which is associated  with harder stools—a sign of slower intestinal transit. Although the overall fecal and blood serotonin levels of people with irritable bowel syndrome were not dramatically different from those of healthy people, these findings suggest that reduced levels of serotonin-producing bacteria may affect gut function.

“In conclusion, we identified human co-isolated L. mucosae and L. ruminis strains that synthesize serotonin in vitro and modulate enteric serotonin levels, enteric innervation, and intestinal transit time in vivo,” the authors say.

Future research, they add, should focus on understanding which conditions promote microbial serotonin production in the gut and whether supplementing serotonin-producing bacteria could help people with constipation or other intestinal motility conditions.