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Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease
  1. Huikuan Chu1,2,
  2. Yi Duan2,3,
  3. Ling Yang1,
  4. Bernd Schnabl2,3
  1. 1 Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  2. 2 Department of Medicine, University of California San Diego, San Diego, California, USA
  3. 3 Department of Medicine, VA San Diego Healthcare System, San Diego, California, USA
  1. Correspondence to Professor Bernd Schnabl, Department of Medicine, University of California, San Diego, CA 92093, USA; beschnabl{at}


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.

  • nonalcoholic steatohepatitis
  • intestinal bacteria
  • intestinal barrier function

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  • Contributors HC, YD and BS: contributed to the conception and design of the work. All authors wrote and critically reviewed and edited the manuscript; approved the final version of the manuscript.

  • Funding This work was supported by National Natural Science Foundation of China (No.81570530, 81370550; to LY) and NIH grants R01 AA020703, R01 AA024726, U01 AA021856 (to BS).

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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