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Alcohol, fungal dysbiosis in the gut and alcoholic liver disease

September 04 2017

Alcohol liver disease (ALD) due to chronic alcohol abuse is characterised by fatty liver and it can lead to severe complications such as alcohol hepatitis, fibrosis and cirrhosis. An-Ming Yang of UCSD, La Jolla, California, USA and many co-authors demonstrate the presence of fungal dysbiosis and systemic antigenaemia in the guts of mice and humans during chronic alcohol abuse (ref). Fungal overgrowth in the gut and translocation of fungal β-glucan into the systemic circulation was observed. These could be controlled by antifungal treatment which also improved the ALD.

ALD has previoulsy been associated with intestinal bacterial dysbiosis including intestinal bacterial overgrowth and a leaky gut barrier. The latter leads to increased translocation of microbial products from the gut into the systemic circulation, which contributes to the progression of ALD. The role of intestinal fungi in ALD has not been studied until recently.

The authors also found a link between β-glucanaemia and hepatic damage by demonstrating that binding of the translocated β-glucan to Dectin 1 on inflammatory cells promoted ALD and hepatic inflammation in an NLRP3- and caspase-1- dependent manner evidenced by increased levels of IL-1β and other secretary components. The immune response to intestinal fungi was found to correlate with the survival of patients. Candida albicans was the most abundant fungal species in the faeces of these patient populations.

In addition to ALD, heavy alcohol consumption has also been linked to oral and gastrointestinal cancers (REF). Ethanol itself is not carcinogenic but its first metabolite acetaldehyde is. Ethanol is mainly metabolised in the liver and this metabolism exposes it to carcinogenic acetaldehyde contributing to hepatic carcinomas. Many gut microorganisms, especially Candida species such as Candida albicans, can also metabolise ethanol to acetaldehyde. This extra-hepatic microbial acetaldehyde production contributes to alcohol related carcinogenesis in the gastrointestinal tract.

Article

Seitz HK, Stickel F. Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer. 2007 Aug;7(8):599-612.