Role of Bile Acids in Metabolic Control

• Published in: Trends in endocrinology and metabolism 2018-01, Vol.29 (1), p.31-41
• Main Authors: Molinaro, Antonio, Wahlström, Annika, Marschall, Hanns-Ulrich
• Format: Article
• Language: English
• Subjects: Animals; bile acids; Bile Acids and Salts - metabolism; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - therapy; farnesoid X receptor; Gastroenterologi; Gastroenterology and Hepatology; Gastrointestinal Microbiome - physiology; gut microbiota; Humans; non-alcoholic fatty liver disease; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - therapy; non-alcoholic steatohepatitis; Obesity - metabolism; Obesity - therapy; obesity surgery; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, G-Protein-Coupled - metabolism; Takeda G protein-coupled receptor 5
• ISSN: 1043-2760; 1879-3061; 1879-3061
• DOI: 10.1016/j.tem.2017.11.002

Bile acids are endocrine molecules that in addition to facilitating the absorption of fat-soluble nutrients regulate numerous metabolic processes, including glucose, lipid, and energy homeostasis. The signaling actions of bile acids are mediated through specific bile-acid-activated nuclear and membrane-bound receptors. These receptors are not only expressed by tissues within the enterohepatic circulation such as the liver and the intestine, but also in other organs where bile acids mediate their systemic actions. In this review, we discuss bile acid signaling and the interplay with the gut microbiota in the pathophysiology of obesity, type 2 diabetes, and non-alcoholic fatty liver disease, and the role of surgical and pharmacological interventions on bile acid profiles and metabolism. Bile acids are endocrine signaling molecules that affect host physiology via activation of bile acid receptors such as FXR and TGR5. Microbes in the gut are responsible for the intestinal modification of bile acids and for the regulation of several hepatic key enzymes involved in bile acid synthesis. Alterations in bile acid homeostasis are often associated with metabolic disease. Bile acid and microbiota interactions via FXR and TGR5 are fundamental for host metabolism and bile acid signaling regulate metabolic pathways in a tissue specific manner. Modulation of intestinal microbiota and consequently of bile acid profiles might affect the treatment of metabolic diseases and the outcome of bariatric surgery, indicating new possible therapeutic avenues. Pre/probiotics and fecal transplantation are tools available to manipulate microbiota and bile acid composition in the host. This has been shown to have a profound effect on host physiology. Improving these techniques could be a reasonable approach to treat metabolic disease.