Abstract
Alcohol-related liver disease is one of the most prevalent types of chronic liver diseases globally. Alcohol-related liver disease begins with fatty liver, which further develops into hepatic inflammation, hepatocyte injury, and progresses to fibrosis and cirrhosis. Compositional changes of gut bacteria and fungi were found in patients with alcohol-related liver disease. However, the functional changes of fungi and correlations between fungi and bacteria have not been investigated. In this study, we first examined the functional capacity of fungi in patients with alcohol-related liver disease using shotgun metagenomics. Among 24 MetaCyc pathways contributed by fungi, superpathway of allantoin degradation in yeast was enriched in patients with alcoholic hepatitis. Furthermore, we compared the predictive power of bacteria versus fungi and found that bacteria performed better than fungi to separate patients with alcoholic hepatitis from non-alcoholic controls and patients with alcohol use disorder. Finally, we investigated the associations between the intestinal fungi and bacteria in alcoholic hepatitis patients. Positive association between fungi and bacteria was found between Cladosporium and Gemmiger, meanwhile negative association was found between Cryptococcus and Pseudomonas in alcoholic hepatitis patients.
Highlights
The human gut microbiota consists of bacteria, eukaryotes, archaea, and viruses, which live symbiotically in the gastrointestinal tract [1]
Body mass index was higher in patients with alcoholic hepatitis compared with patients with alcohol use disorder
We found an altered fungal pathway in patients with alcoholic hepatitis, predicted the diagnosis of alcoholic hepatitis using random forest model, and identified the association between fungi and bacteria in patients with alcoholic hepatitis
Summary
The human gut microbiota consists of bacteria, eukaryotes, archaea, and viruses, which live symbiotically in the gastrointestinal tract [1]. The gut microbiota plays a key role in human health and disease. Alcohol-related liver disease is one of the most prevalent liver diseases worldwide. Alcohol-related liver disease progresses from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Alcoholic hepatitis is a severe form of alcohol-related liver disease and most commonly arises acutely on the background of cirrhosis [2]. Treatment strategies are limited for patients with alcoholic hepatitis
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