The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
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)
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887 · cited 2×
“AST, IU/L 40 (32-59) 36 (30-43) 32 (20-44) 56 (37-71) 0.”
MethodUPARSE: highly accurate OTU sequences from microbial amplicon reads
Edgar, R. C. (2013) · Nature Methods · doi:10.1038/nmeth.2604 · Cited by 16,770 · cited 2×
“0),((23)) and included read error correction, dereplication, chimera filtering, and, finally, de novo clustering into operational taxonomic units (OTUs) at a 97% identity cutoff.”
BackgroundMetagenomic biomarker discovery and explanation
Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W. S., & Huttenhower, C. (2011) · Genome Biology · doi:10.1186/gb-2011-12-6-r60 · Cited by 16,192 · cited 4×
“As assessed with LEfSE at a P value 0.05, the gut microbiome of NASH patients was significantly enriched in six functional categories, compared to those without NASH.”
MethodInfluentialAn obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444 · cited 1×
“Recently, the gut microbiota has gained great attention in metabolic diseases since gut dysbiosis has been demonstrated in obesity,((7,8)) MetS,((9,10)) diabetes,((11,12)) and cardiovascular diseases.”
BackgroundDesign and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791 · cited 1×
“Steatosis, lobular inflammation, ballooning, and liver fibrosis were semiquantitatively evaluated according to the NASH CRN scoring system((19)): F0 5 no fibrosis; F1 5 perisinusoidal or portal/periportal fibrosis; F2 5 perisinusoidal and portal/periportal fibrosis; F3 5 bridging fibrosis; and F4 5 cirrhosis.”
MethodDiet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100 · cited 3×
“AST, IU/L 40 (32-59) 36 (30-43) 32 (20-44) 56 (37-71) 0.”
Self-citationPredictive functional profiling of microbial communities using 16S rRNA marker gene sequences
Langille, M. G. I., Zaneveld, J., Caporaso, J. G., McDonald, D., Knights, D., Reyes, J. A., Clemente, J. C., Burkepile, D. E., Vega Thurber, R. L., Knight, R., et al. (2013) · Nature Biotechnology · doi:10.1038/nbt.2676 · Cited by 9,116 · cited 4×
“To further explore hypotheses linking Bacteroides and Ruminoccocus to severity of NAFLD, we used PICRUSt to estimate the metagenomic profile of the gut microbiota from our patients.((24)) Interestingly, this functional approach showed that more serious NAFLD lesions (i.”
MethodInfluentialUltra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms
Caporaso, J. G., Lauber, C. L., Walters, W. A., Berg-Lyons, D., Huntley, J., Fierer, N., Owens, S. M., Betley, J., Fraser, L., Bauer, M., et al. (2012) · The ISME Journal · doi:10.1038/ismej.2012.8 · Cited by 8,839 · cited 2×
“AST, IU/L 40 (32-59) 36 (30-43) 32 (20-44) 56 (37-71) 0.”
MethodA core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823 · cited 1×
“Recently, the gut microbiota has gained great attention in metabolic diseases since gut dysbiosis has been demonstrated in obesity,((7,8)) MetS,((9,10)) diabetes,((11,12)) and cardiovascular diseases.”
BackgroundHuman gut microbiome viewed across age and geography
Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Dominguez-Bello, M. G., Contreras, M., Magris, M., Hidalgo, G., Baldassano, R. N., Anokhin, A. P., et al. (2012) · Nature · doi:10.1038/nature11053 · Cited by 7,815 · cited 4×
“AST, IU/L 40 (32-59) 36 (30-43) 32 (20-44) 56 (37-71) 0.”
BackgroundInfluential
Flagged first, then by citations
Cited by
Sorted by citations
Mechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
The gut-liver axis in liver disease: Pathophysiological basis for therapy
Albillos, A., de Gottardi, A., & Rescigno, M. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.10.003 · Cited by 2,166
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Noninvasive assessment of liver disease in patients with nonalcoholic fatty liver disease
Castera, L., Friedrich-Rust, M., & Loomba, R. (2019) · Gastroenterology · doi:10.1053/j.gastro.2018.12.036 · Cited by 1,494
The gut-liver axis and the intersection with the microbiome
Tripathi, A., Debelius, J., Brenner, D. A., Karin, M., Loomba, R., Schnabl, B., & Knight, R. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0011-z · Cited by 1,480
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
