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

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Lwaldron, Fatima, WikiWorks

Subjects

Location of subjects
France
Host species Species from which microbiome was sampled (if applicable)
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
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
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

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

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: increased abundance in NASH

NCBI Quality ControlLinks
Bacteroidaceae
Bacteroides

Revision editor(s): WikiWorks

Signature 2

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 ControlLinks
Prevotella
Prevotellaceae

Revision editor(s): WikiWorks

Experiment 2


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Lwaldron, WikiWorks

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

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05


Signature 1

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 3

Description: Relative significant Abundance of Gut Microbiome Taxa in Patients With Significant F 2 Fibrosis and No/Mild Fibrosis (F0/F1 Stage)

Abundance in Group 1: increased abundance in significant fibrosis (F>2)

NCBI Quality ControlLinks
Ruminococcus
Bacteroidaceae
Bacteroides

Revision editor(s): WikiWorks

Signature 2

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 3

Description: Relative significant Abundance of Gut Microbiome Taxa in Patients With Significant F 2 Fibrosis and No/Mild Fibrosis (F0/F1 Stage)

Abundance in Group 1: decreased abundance in significant fibrosis (F>2)

NCBI Quality ControlLinks
Prevotellaceae
Prevotella
Erysipelotrichaceae

Revision editor(s): WikiWorks