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Manipulation of the gut microbiome to treat alcoholic hepatitis
Duan Y, Llorente C, Lang S, et al. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature 2019;575:505–511.
Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease with limited therapeutic options and a high associated mortality. While perturbation of the gut microbiota and gut barrier dysfunction have been previously associated with AH, their specific contribution to the pathogenesis of the condition have been poorly understood until now. In this study, using microbial sequencing and quantitative PCR, the authors identified an increase in levels of the bacterium Enterococcus faecalis in the stool of patients with AH compared with comparator arms. They further demonstrated that an exotoxin produced by these bacteria, cytolysin, is of particular significance, since 89% of cytolysin-positive AH patients died within 180 days compared with 3.8% of cytolysin-negative patients (p<0.0001), with deaths predominantly attributable to liver failure. In alcohol-fed mice, those animals administered a cytolysin-positive strain of E. faecalis developed more severe liver inflammation than those receiving a cytolysin-negative strain of the same bacterium, with cytolysin shown to cause injury to hepatocytes directly. Additionally, germ-free mice colonised with faeces from cytolysin-positive AH patients developed more severe ethanol-induced liver injury, steatosis, inflammation and fibrosis than mice colonised with faeces from cytolysin-negative patients. The authors further demonstrated that administration to these humanised mice of a bacteriophage that specifically targets cytolysin-positive E. faecalis resulted in reduced cytolysin within the liver, and markedly reversed the alcohol-induced liver injury. Not only is cytolysin a potential new biomarker for AH, this study also opens the possibility of ‘precision editing’ of the gut microbiome as a novel targeted approach to treating AH.
Targeting oxidised phospholipids in non-alcoholic steatohepatitis
Sun X, Seidman JS, Zhao P, et al . Neutralization of oxidized phospholipids ameliorates non-alcoholic steatohepatitis. Cell Metab 2020;31(1):189–206.e8. doi: 10.1016/j.cmet.2019.10.014.
Non-alcoholic steatohepatitis (NASH) is a major cause of liver …
Funding The author has not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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