Microbiome as a potential diagnostic and predictive biomarker in severe alcoholic hepatitis

Abstract

BACKGROUND: Severe alcoholic hepatitis (AH) is the most aggressive form of alcohol-related liver disease with high mortality. The microbiome is an emerging therapeutic target in alcohol-related liver disease. AIMS: To investigate the microbiome composition in patients with severe AH, and to determine microbiome recovery after rifaximin treatment in gut bacteria and bacteria derived-extracellular vesicles. METHODS: We enrolled 24 patients with severe AH and 24 healthy controls. Additional faecal samples were collected after 4 weeks in 8 patients with severe AH who completed rifaximin treatment. Treatment response was defined based on Lille score model after 7 days of treatment. Metagenomic profiling was performed using 16S ribosomal RNA amplicon sequencing. RESULTS: Faecal microbiomes of patients with severe AH had lower alpha diversity and higher beta diversity than those of healthy controls in both gut bacteria and extracellular vesicles. Bacilli, Lactobacillales and Veillonella were significantly increased in the gut bacteria of patients with severe AH, and Veillonella, Veillonella parvula group and Lactobacillales were significantly increased in the extracellular vesicles of patients with severe AH. Eubacterium_g23, Oscillibacter and Clostridiales decreased in the gut bacteria of patients with severe AH, and Eubacterium_g23, Oscillibacter and Christensenellaceae decreased in the extracellular vesicles of patients with severe AH. After rifaximin treatment, 17 taxa in the gut bacteria and 23 taxa in extracellular vesicles were significantly restored in patients with severe AH. In common, Veillonella and Veillonella parvula group increased in patients with severe AH and decreased after rifaximin treatment, and Prevotella and Prevotellaceae decreased in patients with severe AH and increased after rifaximin treatment. Treatment non-responders showed a significantly lower abundance of Prevotella at baseline than did treatment responders. CONCLUSION: Dysbiosis was confirmed in severe AH but was alleviated by rifaximin treatment. Taxa associated with severe AH can be candidate biomarkers or therapeutic targets.