SAT-657 The Gut Microbiome Regulates Host Glucose Homeostasis via Peripheral Serotonin

The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find [1] that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin. [1] The gut microbiome regulates host glucose homeostasis via peripheral serotonin. Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19802-19804. Martin AM, Yabut JM, Choo JM, Page AJ, Sun EW, Jessup CF, Wesselingh SL, Khan WI, Rogers GB, Steinberg GR, Keating DJ.