Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease

• Published in: Gut Vol. 68; no. 2; pp. 359 - 370
• Main Authors: Chu, Huikuan, Duan, Yi, Yang, Ling, Schnabl, Bernd
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.02.2019
• Subjects: Bacteria; Bile acids; Body mass index; Cirrhosis; Diet; Ethanol; Exercise; Fatty acids; Fatty liver; Fibrosis; Hepatocellular carcinoma; Hepatology; Immunoglobulins; Intestinal microflora; Intestine; Liver cirrhosis; Liver diseases; Medical research; Metabolism; Metabolites; Microbiota; Microorganisms; Pathogenesis; Pathophysiology; Pediatrics; Permeability; Physical fitness; Signal transduction; Steatosis; Therapeutic applications; Trimethylamine; Veins & arteries; VOCs; Volatile organic compounds; United States > US; nonalcoholic steatohepatitis; intestinal barrier function; intestinal bacteria
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2018-316307

The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis, commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD pathophysiology involves environmental, genetic and metabolic factors, as well as changes in the intestinal microbiota and their products. Dysfunction of the intestinal barrier can contribute to NAFLD development and progression. Although there are technical limitations in assessing intestinal permeability in humans and the number of patients in these studies is rather small, fewer than half of the patients have increased intestinal permeability and translocation of bacterial products. Microbe-derived metabolites and the signalling pathways they affect might play more important roles in development of NAFLD. We review the microbial metabolites that contribute to the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. We discuss the mechanisms by which metabolites produced by microbes might affect disease progression and/or serve as therapeutic targets or biomarkers for NAFLD.