Fecal SCFAs and SCFA-producing bacteria in gut microbiome of human NAFLD as a putative link to systemic T-cell activation and advanced disease
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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.
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Patients with NAFLD have taxonomic alterations in the intestinal microbiome favouring short chain fatty acid-producing bacteria, higher faecal levels of choline metabolites and reduced numbers of regulatory T cells.
“In a recent study, patients with NAFLD were found to have taxonomic alterations in the intestinal microbiome favouring short chain fatty acid-producing bacteria, higher faecal levels of choline metabolites and reduced numbers of regulatory T cells.162”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [162]
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- Authors
- Rau, M., Rehman, A., Dittrich, M., Groen, A. K., Hermanns, H. M., Seyfried, F., Beyersdorf, N., Dandekar, T., Rosenstiel, P., & Geier, A.
- Affiliations
- Universitätsklinikum Würzburg (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- University of Würzburg (DE)
- University Medical Center Groningen (NL)
- Corresponding author
- Geier, Andreas
- ORCID
- Venue
- United European Gastroenterology Journal
- Publisher
- Wiley
- Published
- 2018-12
- Volume
- 6
- Issue
- 10
- Pages
- 1496-1507
- ISSN
- 2050-6406 (ISSN-L)
- 2050-6414
- PMC
- PMC6297934
- OpenAlex
- W2894856581
- Cited by
- 334
- References
- 32
- Citations by year
- 2026: 31 · 2025: 51 · 2024: 66 · 2023: 59 · 2022: 42 · 2021: 42 · 2020: 26 · 2019: 16 · 2015: 1
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- United European Gastroenterology Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- IZKF Würzburg
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, short-chain fatty acids, gut microbiota, SCFA-producing bacteria, Fusobacteriaceae, Fusobacteria, regulatory T cells, Th17/Treg ratio, acetate, propionate, peripheral blood mononuclear cells, immunomodulation, disease progression
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