Role of Microbiota-Derived Metabolites in Alcoholic and Non-Alcoholic Fatty Liver Diseases

Int J Mol Sci. 2021 Dec 31;23(1):426. doi: 10.3390/ijms23010426.

Abstract

Chronic liver disease encompasses diseases that have various causes, such as alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Gut microbiota dysregulation plays a key role in the pathogenesis of ALD and NAFLD through the gut-liver axis. The gut microbiota consists of various microorganisms that play a role in maintaining the homeostasis of the host and release a wide number of metabolites, including short-chain fatty acids (SCFAs), peptides, and hormones, continually shaping the host's immunity and metabolism. The integrity of the intestinal mucosal and vascular barriers is crucial to protect liver cells from exposure to harmful metabolites and pathogen-associated molecular pattern molecules. Dysbiosis and increased intestinal permeability may allow the liver to be exposed to abundant harmful metabolites that promote liver inflammation and fibrosis. In this review, we introduce the metabolites and components derived from the gut microbiota and discuss their pathologic effect in the liver alongside recent advances in molecular-based therapeutics and novel mechanistic findings associated with the gut-liver axis in ALD and NAFLD.

Keywords: alcoholic liver disease; dysbiosis; gut microbiota; gut–liver axis; metabolites; non-alcoholic fatty liver disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Dysbiosis / microbiology
  • Dysbiosis / therapy
  • Gastrointestinal Microbiome*
  • Humans
  • Liver Diseases, Alcoholic / metabolism*
  • Liver Diseases, Alcoholic / microbiology*
  • Liver Diseases, Alcoholic / therapy
  • Metabolome*
  • Models, Biological
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / microbiology*
  • Non-alcoholic Fatty Liver Disease / therapy