Bacteria Engineered\nto Produce Serotonin Modulate\nHost Intestinal Physiology

Bacteria in the gastrointestinal tract play a crucial\nrole in intestinal\nmotility, homeostasis, and dysfunction. Unraveling the mechanisms\nby which microbes impact the host poses many challenges due to the\nextensive array of metabolites produced or metabolized by bacteria\nin the gut. Here, we describe the engineering of a gut commensal bacterium, Escherichia coli Nissle 1917, to biosynthesize the\nhuman metabolite serotonin for examining the effects of microbially\nproduced biogenic amines on host physiology. Upon oral administration\nto mice, our engineered bacteria reach the large intestine, where\nthey produce serotonin. Mice treated with serotonin-producing bacteria\nexhibited biological changes in the gut at transcriptional and physiological\nlevels. This work establishes a novel framework employing engineered\nbacteria to modulate luminal serotonin levels and suggests potential\nclinical applications of modified microbial therapeutics to address\ngut disorders in humans.