Bile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders.
The composition of the bile acid pool is a function of the microbial metabolism of bile acids in the intestine. Perturbations of the microbiota shape the bile acid pool and modulate the activity of bile acid-activated receptors (BARs) even beyond the gastrointestinal tract, triggering various metabolic axes and altering host metabolism. Bile acids, in turn, can also regulate the composition of the gut microbiome at the highest taxonomic levels. Primary bile acids from the host are preferential ligands for the farnesoid X receptor (FXR), while secondary bile acids from the microbiota are ligands for G-protein-coupled bile acid receptor 1 (GPBAR1). In this review, we examine the role of bile acid signaling in the regulation of intestinal microbiota and how changes in bile acid composition affect human metabolism. Bile acids may offer novel therapeutic modalities in inflammation, obesity, and diabetes.
University of Perugia Medical School, Department of Surgery and Biomedical Sciences, Nuova Facoltà di Medicina, Via L. Severi 1-06132, Perugia, Italy. Electronic address: stefano.fiorucci@unipg.it.
Stefano
S
Fiorucci
Azienda Ospedaliera di Perugia, Via L. Severi 1-06132, Perugia, Italy.
Eleonora
E
Distrutti
D050110:Bariatric Surgery / Q000379:methods; D001647:Bile Acids and Salts / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D009765:Obesity / Q000378:metabolism / Q000382:microbiology / Q000601:surgery; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000099150:Receptor, Farnesoid X-Activated
D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; D043562:Receptors, G-Protein-Coupled; D000099150:Receptor, Farnesoid X-Activated; C473772:GPBAR1 protein, human