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

Monika Rau; Ateequr Rehman; Marcus Dittrich; Albert K Groen; Heike M Hermanns; Florian Seyfried; Niklas Beyersdorf; Thomas Dandekar; Philip Rosenstiel; Andreas Geier

doi:10.1177/2050640618804444

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

United European Gastroenterol J. 2018 Dec;6(10):1496-1507. doi: 10.1177/2050640618804444. Epub 2018 Sep 30.

Authors

Affiliations

¹ Department of Medicine II, Division of Hepatology, University Hospital Würzburg, Germany.
² Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Germany.
³ Department of Bioinformatics, Biocenter, University of Würzburg, Germany.
⁴ Department of Pediatrics/Laboratory Medicine, UMCG, Groningen, The Netherlands.
⁵ Department of General and Visceral Surgery, University Hospital Würzburg, Germany.
⁶ Institute for Virology and Immunobiology, University of Würzburg, Germany.

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.

Keywords: Microbiome; NAFLD; SCFA; T-cell activation.