Bacteria Engineered to Produce Serotonin Modulate Host Intestinal Physiology

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