Impaired enteroendocrine cells differentiation signaling pathways through microbiota transfer (1107.12)

Abstract

Recently, we showed that susceptibility to obesity is characterized by an unfavorable microbiome and that the gut chemosensory signature can be transferred via microbiota. To examine whether changes in the signaling pathways controlling differentiation of enteroendocrine cells (EEC) are transmitted through gut microbiota, we assessed gene and protein expression of intestinal bHLH transcription factors, in germ free mice conventionalized with microbiota from obese prone and resistant rats. Gut permeability, intestinal lipid and carbohydrates transporters as well as circulating levels and intestinal protein expression of gut peptides were determined. We showed that obese animals exhibited decreased expression of bHLH transcription factors controlling EECs differentiation (MATH1, NGN3, NEUROD1), increased expression of bHLH factors modulating absorptive enterocyte expression. and decreased number of total EECs L‐, I‐ and S‐cells. This was accompanied by increased gut permeability and expression of lipid and carbohydrates transporters. Transfer of obese gut microbiota replicated obesity‐associated decreased in bHLH transcription factors in germ free mice. These findings demonstrate that gut microbiota modulates complex molecular signaling machinery responsible for EECs differentiation pathways. It shows that susceptibility to obesity and associated microbiome impacts EEC differentiation through downregulation of bHLH transcription factors resulting in reduced EEC number and satiety gut hormone levels.