Gut dysbiosis as a driver in alcohol-induced liver injury

Abstract

Alcohol-related liver disease characterises a broad spectrum of hepatic diseases that result from heavy alcohol use, and include alcohol-related steatosis, steatohepatitis, fibrosis, cirrhosis, and alcoholic hepatitis. Amongst heavy drinkers, progression to more severe forms of alcohol-related liver disease is not universal, with only 20% developing cirrhosis and up to one-third developing alcoholic hepatitis. Non-alcohol-related triggers for severe disease are not well understood, but the intestinal microbiome is thought to be a contributing factor. This review examines the role of the microbiome in mild alcohol-related liver disease, cirrhosis, and alcoholic hepatitis. While most of the literature discusses bacterial dysbiosis, we also discuss the available evidence on fungal (mycobiome) and virome alterations in patients with alcohol-related liver disease. Additionally, we explore the mechanisms by which the microbiome contributes to the pathogenesis of alcohol-related liver disease, including effects on intestinal permeability, bile acid dysregulation, and production of hepatotoxic virulence factors.

Keywords: AH, alcoholic hepatitis; ALD, Alcohol-related liver disease; AUD, alcohol use disorder; Alcohol; Bile acids; CDR, cirrhosis dysbiosis ratio; Cirrhosis; FGF19, fibroblast growth factor 19; FXR, farnesoid X receptor; Hepatitis; LPS, lipopolysaccharide; MELD, model for end-stage liver disease; Microbiome; Mycobiome; PAMPs, pathogen-associated molecular patterns; PPI, proton pump inhibitor; SCFA, short-chain fatty acid; Virome.

Fig. 1

Summary of major microbial changes associated with progression of alcohol-related liver disease. Alcohol-associated dysbiosis is characterised by changes in bacteria, fungi and viruses during the onset and progression of ALD. Dysbiosis contributes to liver disease via different mechanisms, which include increased intestinal permeability, changes in bile acids and in bacterial metabolites such as short-chain fatty acids. ∗Active drinking is independently associated with an increase in faecal secondary bile acids regardless of disease stage. 1^o, primary; 2^o, secondary; ALD, alcohol-related liver disease; BA, bile acid; g, genus; f, family; SCFA, short-chain fatty acid.