Background and Aims: Diabetes mellitus involves many metabolic disorders including a decrease in incretin effect. One of the incretine hormones, Glucagon-Like Peptide-1 (GLP-1) is produced and secreted by enteroendocrine L cells which represent 1% of the intestinal epithelial cells. We have recently shown that bile acid nuclear receptor Farnesoid X Receptor (FXR) activation in enteroendocrine L cells decreases glucose-induced ChREBP-dependant proglucagon gene transcription. By inhibiting glycolysis pathway, FXR also decreases glucose-induced GLP-1 secretion (Trabelsi et al., 2015). The aim of this study is to investigate the role of FXR in the L cell response to other GLP-1 secretagogues and especially to short chain fatty acids (SCFA). SCFA, acetate, propionate and butyrate are metabolites produced by the gut microbiota by fermentation of non digestible polysaccharides (Tremaroli & Bäckhed, 2012). Indeed, in addition to their contribution of 5 to 10% of the daily energetic resources, SCFA are also signalling molecules as they bind to the transmembrane receptor GPR43/FFAR2, thereby promoting GLP-1 secretion by L cells (Psichas et al., 2015 ; Wichmann et al., 2013 ; Tolhurst et al., 2012). Materials and Methods: FXR was activated in vitro in the murine cell line GLUTag and in vivo in C57Bl6/J mice by the synthetic agonist GW4064. GLP-1 secretion tests (ELISA) in response to Butyrate, one of the SCFA, were performed in vitro in GLUTag cells and ex vivo on murine colonic explants. GPR43 mRNA levels were evaluated by qPCR in GLUTag cells incubated with GW4064, in colon from mice treated with GW4064, KO FXR mice and mice treated 3 weeks with colesevelam, a bile acid sequestrant, which display a drastic down regulation of FXR transcriptional activity. Results: FXR activation decreases GLP-1 secretion in response to butyrate both in vitro in GLUTag cells and ex vivo in mouse colonic explants from C57Bl6/J mice treated 5 days by the synthetic FXR agonist GW4064. In parallel, FXR activation in vitro and in vivo decreases GPR43 mRNA levels. As a mirror effect, FXR KO mice and colesevelam treated mice exhibit an increased GPR43 mRNA level in colon. Conclusion: FXR activation decreases GPR43 expression and L cell capacity to respond to SCFA in terms of GLP-1 secretion. Disregulation of FXR in intestine seems to be a good way to increase L cell capacity to respond to glucose and to gut microbiota metabolites and thus to improves metabolic control.