Small intestinal taurochenodeoxycholic acid-FXR axis alters local nutrient-sensing glucoregulatory pathways in rats

•Upper small intestinal infusion of oleic acid or glucose increases glucose tolerance in healthy but not HF-fed rats.•Ileal infusion of oleic acid or glucose increases glucose tolerance in healthy but not HF-fed rats.•Upper small intestinal healthy microbiome transplant enhances nutrient sensing and inhibits FXR via reduced TCDCA levels.•Inhibition of FXR in the upper small intestine or ileum enhances oleic acid sensing to increase glucose tolerance.•Inhibition of upper small intestinal bile salt hydrolase negates oleic acid sensing and activates FXR in the small intestine.