The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

26600078

DOI Digital object identifier for electronic documents.

10.1002/hep.28356

URI

Authors

Boursier J, Mueller O, Barret M, Machado M, Fizanne L, Araujo-Perez F, Guy CD, Seed PC, Rawls JF, David LA, Hunault G, Oberti F, Calès P, Diehl AM

Journal

Hepatology (Baltimore, Md.)

Year

2016

UNLABELLED: 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.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Lwaldron, Fatima, WikiWorks, Victoria

Subjects

Location of subjects: France

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Non-alcoholic fatty liver disease fatty liver disease, nonalcoholic,fatty liver disease, nonalcoholic, susceptibility to, 1,liver disease, alcoholic, susceptibility to, 1,NAFLD - Nonalcoholic Fatty Liver Disease,NAFLD - nonalcoholic fatty liver disease,NAFLD1,non-alcoholic fatty liver,non-alcoholic fatty liver disease,Nonalcoholic Fatty Liver Disease,nonalcoholic fatty liver disease,Non-alcoholic fatty liver disease

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Non-NASH

Group 1 name Corresponds to the case (exposed) group for case-control studies: NASH

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: NAFLD was defined as liver steatosis on liver biopsy after exclusion of concomitant steatosis-inducing drugs, excessive alcohol consumption (>210 g/week in men or >140 g/week in women), chronic hepatitis B or C infection, and histological evidence of other concomitant chronic liver disease. NASH was defined as the presence of each of the three following conditions: steatosis grade 1; lobular inflammation grade 1; and ballooning grade 1. “Significant fibrosis” was defined as fibrosis stage F2.

Group 0 sample size Number of subjects in the control (unexposed) group: 22

Group 1 sample size Number of subjects in the case (exposed) group: 35

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 2 months

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Logistic Regression

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.1

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: blood pressure, body mass index, diabetes mellitus, hypertriglyceridemia, metabolic syndrome, HDL cholesterol change measurement

Signature 1

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Source: Table 2 + text

Description: Relative significant Abundance of Gut Microbiome Taxa in Patients With NASH and Without NASH

Abundance in Group 1: increased abundance in NASH

NCBI	Quality Control	Links
Bacteroidaceae
Bacteroides

Revision editor(s): WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks

Source: Table 2 + text

Description: Relative significant Abundance of Gut Microbiome Taxa in Patients With NASH and Without NASH

Abundance in Group 1: decreased abundance in NASH

NCBI	Quality Control	Links
Prevotella
Prevotellaceae

Revision editor(s): WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: mild fibrosis (F 0-1)

Group 1 name Corresponds to the case (exposed) group for case-control studies: significant fibrosis (F>2)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: NAFLD was defined as liver steatosis on liver biopsy after exclusion of concomitant steatosis-inducing drugs, excessive alcohol consumption (>210 g/week in men or >140 g/week in women), chronic hepatitis B or C infection, and histological evidence of other concomitant chronic liver disease. NASH was defined as the presence of each of the three following conditions: steatosis grade 􏰃1; lobular nflammation grade 􏰃1; and ballooning grade 􏰃1. “Significant fibrosis” was defined as fibrosis stage F􏰃2.

Group 0 sample size Number of subjects in the control (unexposed) group: 30

Group 1 sample size Number of subjects in the case (exposed) group: 27

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified