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Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
Open accessAbstract
Background Animal data suggest a role of the gut-liver axis in progression of alcoholic liver disease (ALD), but human data are scarce especially for early disease stages.Methods We included patients with alcohol use disorder (AUD) who follow a rehabilitation program and matched healthy controls. We determined intestinal epithelial and vascular permeability (IP) (using urinary excretion of 51Cr-EDTA, fecal albumin content, and immunohistochemistry in distal duodenal biopsies), epithelial damage (histology, serum iFABP, and intestinal gene expression), and microbial translocation (Gram – and Gram + serum markers by ELISA). Duodenal mucosa-associated microbiota and fecal microbiota were analyzed by 16 S rRNA sequencing. ALD was staged by Fibroscan® (liver stiffness, controlled attenuation parameter) in combination with serum AST, ALT, and CK18-M65.Results Only a subset of AUD patients had increased 51Cr-EDTA and fecal albumin together with disrupted tight junctions and vasculature expression of plasmalemma Vesicle-Associated Protein-1. The so-defined increased intestinal permeability was not related to changes of the duodenal microbiota or alterations of the intestinal epithelium but associated with compositional changes of the fecal microbiota. Leaky gut alone did not explain increased microbial translocation in AUD patients. By contrast, duodenal dysbiosis with a dominance shift toward specific potential pathogenic bacteria genera (Streptococcus, Shuttleworthia, Rothia), increased IP and elevated markers of microbial translocation characterized AUD patients with progressive ALD (steato-hepatitis, steato-fibrosis).Conclusion Progressive ALD already at early disease stages is associated with duodenal mucosa-associated dysbiosis and elevated microbial translocation. Surprisingly, such modifications were not linked with increased IP. Rather, increased IP appears related to fecal microbiota dysbiosis.
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“Alcoholic liver disease (ALD) is associated with gut microbial dysbiosis,113, 114, 115”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [113]
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Background
Metadata
- Authors
- Maccioni, L., Gao, B., Leclercq, S., Pirlot, B., Horsmans, Y., De Timary, P., Leclercq, I., Fouts, D., Schnabl, B., & Stärkel, P.
- Affiliations
- UCLouvain (BE)
- University of California San Diego (US)
- Cliniques Universitaires Saint-Luc (BE)
- Department of Adult Psychiatry, Cliniques Universitaires Saint-Luc, Brussels, Belgium
- J. Craig Venter Institute (US)
- Corresponding author
- Stärkel, Peter
- ORCID
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2020-06-26
- Volume
- 12
- Issue
- 1
- Pages
- 1782157
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC7524402
- OpenAlex
- W3037663071
- Cited by
- 174
- References
- 58
- Citations by year
- 2026: 25 · 2025: 33 · 2024: 31 · 2023: 29 · 2022: 27 · 2021: 22 · 2020: 7
- FWCI
- 6.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Gut Microbes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fonds De La Recherche Scientifique - FNRS (J.0146.17, T.0217.18)
- National Institutes of Health (U01 AA026939, R01 AA24726)
- Université Catholique de Louvain (ARC 2018)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- alcoholic liver disease, alcoholism, intestinal permeability, leaky gut, microbial translocation, gut-liver axis, duodenal microbiota, duodenal mucosa, tight junctions, intestinal epithelial damage, Streptococcus, Shuttleworthia, Rothia, liver fibrosis, steatohepatitis
- MeSH terms
- Gastrointestinal Microbiome, Adult, Alcoholism, Bacteria, Capillary Permeability, Duodenum, Feces, Female, Humans, Intestinal Mucosa, Liver, Liver Diseases, Alcoholic, Male, Middle Aged, RNA, Ribosomal, 16S, Dysbiosis
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