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Fecal SCFAs and SCFA-producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T-cell activation and advanced disease.

Abstract：

Background:Intestinal microbiota and their metabolites (e.g. short-chain fatty acids (SCFAs)) may influence nonalcoholic fatty liver disease (NAFLD). Objective:The objective of this article is to analyze gut bacterial diversity together with fecal SCFA concentrations and immunophenotyping of peripheral blood in histology-proven NAFLD patients. Methods:Thirty-two NAFLD patients (14 nonalcoholic fatty liver (NAFL), 18 nonalcoholic steatohepatitis (NASH)) and 27 healthy controls (HCs)) were included in this study. Bacterial communities in feces were profiled by 16S ribosomal RNA gene sequencing of the V3-V4 region. Fecal SCFA levels were analyzed by high-performance liquid chromatography. Fluorescence-activated cell sorting analysis was performed of peripheral blood mononuclear cells. Results:NASH patients were characterized by higher abundance of Fusobacteria and Fusobacteriaceae compared to NAFL and HCs. Conforming to our finding that NAFLD patients had higher fecal acetate and propionate levels, taxonomical differences of fecal bacteria were dominated by SCFA-producing bacteria. Higher fecal propionate and acetate levels were associated with lower resting regulatory T-cells (rTregs) (CD4+CD45RA+CD25++) as well as higher Th17/rTreg ratio in peripheral blood as immunological characteristics of NASH patients. Conclusions:NASH patients are characterized by a different gut microbiome composition with higher fecal SCFA levels and higher abundance of SCFA-producing bacteria in NAFLD. These changes are associated with immunological features of disease progression. Our data suggest an important role of the intestinal microbiome and immunomodulatory bacterial metabolites in human NAFLD.

journal_name

United European Gastroenterol J

journal_title

United European gastroenterology journal

authors

Rau M,Rehman A,Dittrich M,Groen AK,Hermanns HM,Seyfried F,Beyersdorf N,Dandekar T,Rosenstiel P,Geier A

doi

10.1177/2050640618804444

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1496-1507

issue

eissn

2050-6406

issn

2050-6414

pii

10.1177_2050640618804444

journal_volume

pub_type

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Fecal SCFAs and SCFA-producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T-cell activation and advanced disease.