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The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota
Open accessAbstract
Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of NAFLD lesions. We aimed to evaluate the association between gut dysbiosis and severe NAFLD lesions, that is, nonalcoholic steatohepatitis (NASH) and fibrosis, in a well‐characterized population of adult NAFLD. Fifty‐seven patients with biopsy‐proven NAFLD were enrolled. Taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Thirty patients had F0/F1 fibrosis stage at liver biopsy (10 with NASH), and 27 patients had significant F≥2 fibrosis (25 with NASH). Bacteroides abundance was significantly increased in NASH and F≥2 patients, whereas Prevotella abundance was decreased. Ruminococcus abundance was significantly higher in F≥2 patients. By multivariate analysis, Bacteroides abundance was independently associated with NASH and Ruminococcus with F≥2 fibrosis. Stratification according to the abundance of these two bacteria generated three patient subgroups with increasing severity of NAFLD lesions. Based on imputed metagenomic profiles, Kyoto Encyclopedia of Genes and Genomes pathways significantly related to NASH and fibrosis F≥2 were mostly related to carbohydrate, lipid, and amino acid metabolism. Conclusion: NAFLD severity associates with gut dysbiosis and a shift in metabolic function of the gut microbiota. We identified Bacteroides as independently associated with NASH and Ruminococcus with significant fibrosis. Thus, gut microbiota analysis adds information to classical predictors of NAFLD severity and suggests novel metabolic targets for pre‐/probiotics therapies. (H epatology 2016;63:764–775)
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“Boursier et al. found that NAFLD severity was associated with gut dysbiosis and a shift in the metabolic function of the gut microbiota with Bacteroides independently associated with the occurrence of NASH, and Ruminococcus with the presence of significant fibrosis [230].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [230]
In the citing paper
“Likewise, a number of studies have demonstrated alterations of the gut microbiota in earlier stages of liver disease 35,36 as well as in animal models16,31.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [36]
In the citing paper
“However, bacterial abundance patterns were not consistent between studies, with levels of Bacteroidetes increased in some studies36,56 and decreased in other studies57,58, and a substantial overlap with healthy individuals59.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [36]
In the citing paper
“Interestingly, Ruminococcaceae have been found to be enriched in samples from fibrotic patients with NAFLD/NASH36,37, supporting their role in the pathogenesis of other chronic liver diseases that also associate with impaired intestinal barrier function.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [37]
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“As well, in those studies it was shown that NALFD/NASH in patients associated with increased abundance of Bacteroides abundance36,37.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [37]
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Metadata
- Authors
- Boursier, J., Mueller, O., Barret, M., Machado, M., Fizanne, L., Araujo‐Perez, F., Guy, C. D., Seed, P. C., Rawls, J. F., David, L. A., Hunault, G., Oberti, F., Calès, P., & Diehl, A. M.
- Affiliations
- Centre Hospitalier Universitaire d'Angers (FR)
- Duke University (US)
- Institut de Recherche en Horticulture et Semences (FR)
- Duke Medical Center (US)
- HIFIH Laboratory, UPRES 3859, SFR 4208,LUNAM University,Angers,France
- Department of Pediatrics,Duke University Medical Center,Durham,NC
- Corresponding author
- Boursier, Jérôme
- ORCID
- Venue
- Hepatology
- Published
- 2016-01-13
- Volume
- 63
- Issue
- 3
- Pages
- 764-775
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC4975935
- OpenAlex
- W2178380008
- Cited by
- 1,483
- References
- 51
- Citations by year
- 2026: 105 · 2025: 162 · 2024: 180 · 2023: 190 · 2022: 161 · 2021: 191 · 2020: 154 · 2019: 132 · 2018: 91 · 2017: 74 · 2016: 37
- FWCI
- 29.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Association Française pour l'Etude du Foie
- Société Nationale Française de Gastro-Entérologie
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK106633, R56DK106633, R01DK053792)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, liver fibrosis, gut dysbiosis, gut microbiota, Bacteroides, Ruminococcus, Prevotella, NAFLD severity, carbohydrate metabolism, lipid metabolism, amino acid metabolism, probiotics
- MeSH terms
- Gastrointestinal Microbiome, Aged, Feces, Female, Fibrosis, Humans, Liver, Male, Middle Aged, Metagenome, Dysbiosis, Non-alcoholic Fatty Liver Disease
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