Antibiotic induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism. AIMD

Antibiotic induced microbiome depletion (AIMD) has been used frequently to study the role of the gut microbiome in pathological conditions. However, unlike germ-free mice, the effects of AIMD on host metabolic homeostasis is unknown. We investigated the effects of AIMD in normal-chow fed mice to understand its effects on gut homeostasis, luminal signaling, and metabolism. We show that AIMD decreases baseline serum glucose levels, reduces glucose surge in a tolerance test, and improves insulin sensitivity without altering food intake or body adiposity. These occur in the setting of decreased luminal SCFAs, especially butyrate, and secondary bile acid (BA) pool, which affects whole-body BA metabolism. AIMD mice have altered cecal gene expression and gut signaling, particularly of GLP-1. Extensive tissue remodeling and decreased availability of SCFAs shift enterocyte metabolism toward glucose utilization. Hence, AIMD alters whole-body glucose homeostasis by potentially converting the gut into a glucose sink.