Alcoholic liver disease, which ranges from mild disease to alcoholic hepatitis and cirrhosis, is a leading cause of morbidity and mortality worldwide. Alcohol intake can lead to changes in gut microbiota composition, even before liver disease development. These alterations worsen with advancing disease and could be complicit in disease progression. Microbial function, especially related to bile acid metabolism, can modulate alcohol-associated injury even in the presence of cirrhosis and alcoholic hepatitis. Microbiota changes might also alter brain function, and the gut–brain axis might be a potential target to reduce alcoholic relapse risk. Gut microbiota manipulation including probiotics, faecal microbial transplant and antibiotics has been studied in alcoholic liver disease with varying success. Further investigation of the modulation of the gut–liver axis is relevant, as most of these patients are not candidates for liver transplantation. This Review focuses on clinical studies involving the gut microbiota in patients with alcoholic liver disease across the spectrum from alcoholic fatty liver to cirrhosis and alcoholic hepatitis. Specific alterations in the gut–liver–brain axis that are complicit in the interactions between the gut microbiota and alcohol addiction are also reviewed.
Alcohol affects many organ systems, but alcoholic liver disease develops in selected patients and ranges from simple steatosis to inflammation, cirrhosis and alcoholic hepatitis.
Gut microbiota composition and function, especially bile acid physiology, are affected throughout the spectrum of alcohol use disorder, and these changes can improve after alcohol cessation in patients without alcoholic liver disease.
In patients who have substantial liver fibrosis, gut microbial changes occur in parallel to liver injury, with an increase in endotoxin-producing and a reduction in autochthonous bacterial taxa, which continue through active drinking in cirrhosis until alcoholic hepatitis.
Functional microbial changes, in particular, hepatic bile acid production and bacterial biotransformation, are altered in parallel with the disease stages and differ between actively drinking patients with cirrhosis and those with alcoholic hepatitis.
Alcohol use disorder can also affect the gut–brain axis, which could potentiate further misuse and affective disorders and hasten the development of hepatic encephalopathy.
Strategies that address both alcohol cessation and microbiota alteration are needed for meaningful improvement in the natural history of this multifaceted disorder.
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This manuscript was partly supported by VA Merit Review I0CX001076, NCATS R21TR002024 to J.S.B.
J.S.B. declares no competing interests.
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Bajaj, J.S. Alcohol, liver disease and the gut microbiota. Nat Rev Gastroenterol Hepatol 16, 235–246 (2019). https://doi.org/10.1038/s41575-018-0099-1
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