Bile acids are signaling molecules, which coordinately regulate metabolism and inflammation via the nuclear farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in bile acid, lipid and carbohydrate metabolism, energy expenditure, and inflammation by acting predominantly in entero-hepatic tissues, but also in peripheral organs. In this review, we discuss the most recent findings on the inter-organ signaling and interplay with the gut microbiota of bile acids and their receptors in meta-inflammation, with a focus on their pathophysiological roles in obesity, type 2 diabetes, dyslipidemia and non-alcoholic steatohepatitis and their potential therapeutic applications.