Chen F, Esmaili S, Rogers GB, et al. - Among 538 Caucasian patients with nonalcoholic fatty liver disease (NAFLD) and 30 lean healthy controls, researchers tested the assumption that the pathogenesis of lean and obese NAFLD and their distinct metabolic and histological profiles was caused by more than just differences in body weight and BMI. The role of bile acids (BAs) and the gut microbiome in the pathogenesis of lean NAFLD were examined. According to findings, lean NAFLD patients had a more favorable metabolic and histological profile as compared with nonlean NAFLD patients. In NAFLD, the BA levels were significantly higher with advanced vs earlier stages of liver fibrosis. Treating mice with an apical sodium-dependent BA transporter inhibitor (SC-435) led to marked increases in fgf15, a shift in BA and microbiota profiles, and improved steatohepatitis in the lean model. Differences in metabolic adaptation between patients with lean and nonlean NAFLD clarify the pathophysiology and provide treatment options, at least in part.