Characterization of Gut Microbiomes in Nonalcoholic Steatohepatitis (NASH) Patients: A Connection Between Endogenous Alcohol and NASH

Oct 12, 2012Hepatology (Baltimore, Md.)

Gut bacteria in nonalcoholic fatty liver disease linked to natural alcohol production

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Abstract

NASH patients exhibited significantly elevated blood ethanol levels compared to healthy subjects and obese non-NASH patients.

NASH is associated with a distinct gut microbiome composition compared to obese and healthy children.
Microbiome samples clustered primarily based on disease status, indicating differences in gut bacteria linked to NASH.
Proteobacteria, Enterobacteriaceae, and Escherichia were the only groups showing significant differences between obese and NASH microbiomes.
NASH patients had a higher abundance of alcohol-producing bacteria, which may contribute to liver inflammation.
The unique gut microbial patterns in NASH could serve as potential targets for future interventions or markers for the disease.

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UNLABELLED: Nonalcoholic 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 ribosomal RNA pyrosequencing. In addition, peripheral blood ethanol was analyzed to monitor endogenous ethanol production of 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 levels between healthy subjects and obese patients (with or without NASH), and relatively fewer differences were observed between 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 types exhibiting significant difference between obese and NASH microbiomes. Similar blood-ethanol concentrations were observed between healthy subjects and obese non-NASH patients, but NASH patients exhibited significantly elevated blood ethanol levels.

CONCLUSIONS: The increased abundance of alcohol-producing bacteria in NASH microbiomes, 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 NASH, obese, and healthy controls could offer a target for intervention or a marker for disease.

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Characterization of Gut Microbiomes in Nonalcoholic Steatohepatitis (NASH) Patients: A Connection Between Endogenous Alcohol and NASH

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