Bile acids and microbes in metabolic disease

Figure 3 Mechanism by which bile acid metabolites and gut microbes alleviate metabolic diseases. Bile acid metabolites, e.g., bile acid sequestrants (BASs), enter the liver via receptor-mediated pathways. As a result of their effects, mitochondrial oxidative phosphorylation is stimulated; HMGCoAR, LDLR, and SREBP2 gene expression is induced; incretin and cholecystokinin levels are increased; and the abundance of intestinal bacteria is increased, reducing the levels of triglyceride (TG), very-low-density lipoprotein (VLDL), and cholesterol in the blood. By increasing the expression of ZO-1, occludin, and claudin-3 in the gut lumen, probiotics facilitate tight junction proteins, preventing macrophage infiltration and metabolic endotoxemia. In contrast, BAS improves colonic motility; increases glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin secretion; and regulates carbohydrate, fat, and energy metabolism, thereby reducing blood glucose, TG, cholesterol, and VLDL levels and improving insulin sensitivity and liver function. Because of their anti-inflammatory, antidiabetic, and antiobesity properties, BASs and gut microbes alleviate metabolic diseases. CDCA: Chenodeoxycholic acid; TDCA: Taurodeoxycholic acid; GLP-1: Glucagon-like peptide-1; SCFAs: Short-chain fatty acids; LPS: Lipopolysaccharide; PYY: Peptide YY; FXR: Farnesoid X receptor; CCK: Cholecystokinin; TG: Triglycerides; LDLR: Low-density lipoprotein; NKT: natural killer T.