The human gut microbiota can synthesize bioactive serotonin!

Fascinating article ("Identification of human gut bacteria that produce bioactive serotonin and promote colonic innervation", link) by a University of Gothenburg-led group (although I recognize many great scientists from other labs, including Jan-Peter van Pijkeren of University of Wisconsin-Madison) showing that human gut bacteria can synthesize bioactive serotonin.

It was not clear until now whether and how the gut microbiota might be able to "produce" this important molecule, which is primarily produced by gut lining cells (95% of serotonin is produced in the gut) called enterochromaffin (EC) cells. EC cells act as chemosensors, detecting nutrients, irritants, and mechanical forces, and play a crucial role in regulating digestion by influencing motility, secretion, and nutrient absorption. They also communicate with the nervous system and immune cells to affect processes like gut-brain axis signaling, visceral pain, and immune response. Dysfunction of EC cells can contribute to various gastrointestinal disorders, and specifically lower serotonin levels have been associated with irritable bowel syndrome (IBS).

"The study identified a consortium of two human gut bacteria that synthesizes serotonin in vitro and elevates fecal serotonin levels, colonic neuronal density, and serotonin-immunoreactive neurons when introduced into germ-free, serotonin-deficient mice. The consortium normalizes intestinal transit time in germ-free wild-type mice." Individuals with IBS also had decreased fecal abundance in one of the two bacterial species. Identifying and validating the consortium of two bacterial species is an enormous amount of work. The ability of one of the bacterial species (Limosilactobacillus mucosae) to decarboxylate

5-hydroxytryptophan (5-HTP) into serotonin (5-HT) is the key. The other species (Ligilactobacillus ruminis) does not produce serotonin is required to enable the other consortium member's decarboxylase activity. The nature of the context-dependent interaction(s) between the consortium members is not elucidated: metabolic cross-feeding, environmental modification and/or indirect metabolic support may play a role. Knowing under what conditions this consortium is "activated" to produce serotonin remains a key question with exciting downstream clinical potential.

This also suggests a genetic engineering route to turbo-charge serotonin production in bacterial species that already have the biosynthetic decarboxylase ability.