NUTRITION: Edited by Eamonn M.M. QuigleyBile acids as metabolic regulatorsLi, Tianganga; Chiang, John Y.L.bAuthor Information aDepartment of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, Kansas bDepartment of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA Correspondence to Tiangang Li, Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA. Tel: +1 913 588 9974; e-mail: [email protected] Current Opinion in Gastroenterology: March 2015 - Volume 31 - Issue 2 - p 159-165 doi: 10.1097/MOG.0000000000000156 Buy Metrics Abstract Purpose of review This review focuses on the latest understanding of the molecular mechanisms underlying the complex interactions between intestine and liver bile acid signaling, gut microbiota, and their impact on whole-body lipid, glucose and energy metabolism. Recent findings Hepatic bile acid synthesis is tightly regulated by the bile acid negative feedback mechanisms. Modulating the enterohepatic bile acid signaling greatly impacts the whole-body metabolic homeostasis. Recently, a positive feedback mechanism through intestine farnesoid X receptor (FXR) antagonism has been proposed to link gut microbiota to the regulation of bile acid composition and pool size. Two studies identified intestine Diet1 and hepatic SHP-2 as novel regulators of CYP7A1 and bile acid synthesis through the gut–liver FXR–fibroblast growth factor 15/19–FGF receptor four signaling axis. New evidence suggests that enhancing bile acid signaling in the distal ileum and colon contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery. Summary Small-molecule ligands that target TGR5 and FXR have shown promise in treating various metabolic and inflammation-related human diseases. New insights into the mechanisms underlying the bariatric surgery and bile acid sequestrant treatment suggest that targeting the enterohepatic circulation to modulate gut–liver bile acid signaling, incretin production and microbiota represents a new strategy to treat obesity and type 2 diabetes. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.