Characterization of the gut microbiome in non-alcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH.


Non-alcoholic steatohepatitis (NASH) is a serious liver disease associated with obesity. Characterized by metabolic syndrome, hepatic steatosis and liver inflammation, NASH is believed to be under the influence of the gut microflora. Here the composition of gut bacterial communities of NASH, obese and healthy children was determined by 16S rRNA pyrosequencing. In addition, peripheral blood ethanol was analyzed to monitor endogenous ethanol production of the patients and healthy controls. UniFrac based principle coordinates analysis indicated that most of the microbiome samples clustered by disease status. Each group was associated with a unique pattern of enterotypes. Differences were abundant at phylum, family and genus level between the healthy subjects and the obese patients (with or without NASH) and relatively fewer differences were observed between the obese and the NASH microbiomes. Among those taxa with greater than 1% representation in any of the disease groups, Proteobacteria, Enterobacteriaceae and Escherichia were the only phylum, family and genus exhibiting significant difference between the obese and the NASH microbiome. Similar blood ethanol concentration was observed between healthy subjects and obese non-NASH patients, but NASH patients exhibited significantly elevated blood ethanol level. CONCLUSIONS: The increased abundance of alcohol producing bacteria in NASH microbiome, the elevated blood ethanol concentration in NASH patients, and the well-established role of alcohol metabolism in oxidative stress and consequently liver inflammation suggest a role for alcohol producing microbiota in the pathogenesis of NASH. We postulatae that the distinct composition of the gut microbiome among NASH, obese and normals could offer a target for intervention or a marker for disease. (HEPATOLOGY 2012.).
Copyright © 2012 American Association for the Study of Liver Diseases.

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