Cecal transcriptome by Next Generation Sequencing of WT C57Bl/6 mice treated with water (vehicle) or with antibiotics (AIMD) to induce microbiome depletion .

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 metabolism 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, which decreases luminal Firmicutes and Bacteroidetes species, decreases baseline serum glucose levels, reduces glucose surge in a tolerance test, and improves insulin sensitivity without altering adiposity. These occur in the setting of decreased luminal short-chain fatty acids (SCFAs), especially butyrate, and secondary bile acid (BA) pool, which affects whole-body BA metabolism. In mice, AIMD alters cecal gene expression and gut GLP-1 signaling. Extensive tissue remodeling and decreased availability of SCFAs shift colonocyte metabolism toward glucose utilization. Hence, AIMD alters whole-body glucose homeostasis by potentially shifting colonocyte energy utilization from SCFAs to glucose. Cecum mRNA profile of WT C57Bl/6 mice treated for 30 days with a cocktail of antibiotics twice daily by oral gavage (AIMD) or water (vehicle).