Gut microbiome of NASH patients, obese patients and healthy controls. human gut metagenome

Non-alcoholic steatohepatitis (NASH) is the serious form of non-alcoholic fatty liver disease (NAFLD), associated with obesity and responsible for 10% of liver transplants in the US. The development and progression of NASH is believed to be under the influence of the gut microbiota. Here we describe the composition of gut bacterial communities of NASH and obese patients and healthy control individuals. UniFrac based principle coordinates analysis indicated that NASH and obese microbiomes clustered by disease status. A unique pattern of enterotypes was associated with each group. 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 study 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. 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 postulate that the distinct composition of the gut microbiome among the NASH, the obese and the normals could offer a target for intervention. Stool samples collected from adolescents of the following health status: 1) non-alcoholic steatohepatitis; 2) obese; 3) healthy.