Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease.
Adolescent
Bacteria
/ classification
Case-Control Studies
Child
Cross-Sectional Studies
DNA, Bacterial
/ genetics
Dysbiosis
Feces
/ microbiology
Female
Gastrointestinal Microbiome
Host-Pathogen Interactions
Humans
Intestines
/ microbiology
Liver Cirrhosis
/ diagnosis
Male
Metagenome
Non-alcoholic Fatty Liver Disease
/ complications
Prospective Studies
RNA, Ribosomal, 16S
/ genetics
Ribotyping
Severity of Illness Index
Flagellin
Intestinal Microbiota
Lipopolysaccharide
Pediatric
Journal
Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
28
08
2018
revised:
14
06
2019
accepted:
21
06
2019
pubmed:
1
7
2019
medline:
23
10
2019
entrez:
1
7
2019
Statut:
ppublish
Résumé
The intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD. We performed a prospective, observational, cross-sectional study of 87 children (age range, 8-17 years) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiome composition and functions were assessed using 16S ribosomal RNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis. Fecal microbiomes of children with NAFLD had lower α-diversity than those of control children (3.32 vs 3.52, P = .016). Fecal microbiomes from children with nonalcoholic steatohepatitis (NASH) had the lowest α-diversity (control, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH, 2.97; P = .001). High abundance of Prevotella copri was associated with more severe fibrosis (P = .036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomes from children with NASH (P < .001). Classification and regression tree model with level of alanine aminotransferase and relative abundance of the lipopolysaccharide pathway gene encoding 3-deoxy-d-manno-octulosonate 8-phosphate-phosphatase identified patients with NASH with an area under the receiver operating characteristic curve value of 0.92. Genes involved in flagellar assembly were enriched in the fecal microbiomes of patients with moderate to severe fibrosis (P < .001). Classification and regression tree models based on level of alanine aminotransferase and abundance of genes encoding flagellar biosynthesis protein had good accuracy for identifying case children with moderate to severe fibrosis (area under the receiver operating characteristic curve, 0.87). In an analysis of fecal microbiomes of children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiome might contribute to the pathogenesis of NAFLD and be used as markers of disease or severity.
Sections du résumé
BACKGROUND & AIMS
The intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD.
METHODS
We performed a prospective, observational, cross-sectional study of 87 children (age range, 8-17 years) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiome composition and functions were assessed using 16S ribosomal RNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis.
RESULTS
Fecal microbiomes of children with NAFLD had lower α-diversity than those of control children (3.32 vs 3.52, P = .016). Fecal microbiomes from children with nonalcoholic steatohepatitis (NASH) had the lowest α-diversity (control, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH, 2.97; P = .001). High abundance of Prevotella copri was associated with more severe fibrosis (P = .036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomes from children with NASH (P < .001). Classification and regression tree model with level of alanine aminotransferase and relative abundance of the lipopolysaccharide pathway gene encoding 3-deoxy-d-manno-octulosonate 8-phosphate-phosphatase identified patients with NASH with an area under the receiver operating characteristic curve value of 0.92. Genes involved in flagellar assembly were enriched in the fecal microbiomes of patients with moderate to severe fibrosis (P < .001). Classification and regression tree models based on level of alanine aminotransferase and abundance of genes encoding flagellar biosynthesis protein had good accuracy for identifying case children with moderate to severe fibrosis (area under the receiver operating characteristic curve, 0.87).
CONCLUSIONS
In an analysis of fecal microbiomes of children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiome might contribute to the pathogenesis of NAFLD and be used as markers of disease or severity.
Identifiants
pubmed: 31255652
pii: S0016-5085(19)41037-8
doi: 10.1053/j.gastro.2019.06.028
pmc: PMC6756995
mid: NIHMS1532962
pii:
doi:
Substances chimiques
DNA, Bacterial
0
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Observational Study
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1109-1122Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000100
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK088831
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061713
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061730
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK061730
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
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