Evidence map›Paper›PMID 31255652›Full record

Observational studyGastroenterology2019

Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease.

Jeffrey B Schwimmer, Jethro S Johnson, Jorge E Angeles, Cynthia Behling, Patricia H Belt, Ingrid Borecki, Craig Bross, Janis Durelle, Nidhi P Goyal, Gavin Hamilton and 12 more

Registry-linked trialOpen access · greenAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07731360 (A Non-Invasive Diagnostic Panel for MASLD in Children With Obesity), which is not on this map. Cited by 175 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 6 pooled it
23.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07731360 not yet recruitingnot on this mapstarted 2026, after this paper: background citation

A Non-Invasive Diagnostic Panel for MASLD in Children With Obesity: Evaluation of a Multiparametric Biomarker Panel and Genetic Risk Score Using LASSO-Regularized Logistic Regression - The PedMASLD-MultiOmics Pilot Study

TypeobservationalSponsorKayseri City HospitalRan2026 to 2027Enrolled180ConditionsMetabolic Dysfunction-Associated Steatotic Liver Disease, Pediatric Obesity, Insulin Resistance SyndromeArmsNon-Invasive Multi-Parameter Diagnostic Panel
3 · Its place in the literature

Who cites it

175 citing papers in PubMed, 6 syntheses or guidelines pooled it, 288 citations in OpenAlex.

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  11. Gut Microbial Topology and Metabolic Signatures Associated With Colorectal Neoplasia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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115 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 7 institutions in 1 country.

Jeffrey B SchwimmerDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California.
Jethro S JohnsonThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Jorge E AngelesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.
Cynthia BehlingDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Pathology, Sharp Medical Center, San Diego, California.
Patricia H BeltJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Ingrid BoreckiThe McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri.
Craig BrossDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.
Janis DurelleDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.
Nidhi P GoyalDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California.
Gavin HamiltonLiver Imaging Group, Department of Radiology, University of California, San Diego, California.
Mary L HoltzDepartment of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin; Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
Joel E LavineDepartment of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Columbia University, New York, New York.
Makedonka MitrevaThe McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri.
Kimberly P NewtonDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California; Department of Gastroenterology, Rady Children's Hospital San Diego, San Diego, California.
Amy PanDepartment of Pediatrics, Division of Quantitative Health Sciences, The Medical College of Wisconsin, Milwaukee, Wisconsin.
Pippa M SimpsonDepartment of Pediatrics, Division of Quantitative Health Sciences, The Medical College of Wisconsin, Milwaukee, Wisconsin.
Claude B SirlinLiver Imaging Group, Department of Radiology, University of California, San Diego, California.
Erica SodergrenThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Rahul TyagiThe McDonnell Genome Institute, Washington University in St. Louis, St. Louis, Missouri.
Katherine P YatesJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
George M WeinstockThe Jackson Laboratory for Genomic Medicine, Farmington, Connecticut.
Nita H SalzmanDepartment of Pediatrics, Division of Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin; Center for Microbiome Research, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: nsalzman@mcw.edu.
University of California San Diego · USMedical College of Wisconsin · USJackson Laboratory · USJames S. McDonnell Foundation · USJohns Hopkins University · USColumbia University · USSharp Memorial Hospital · US

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Continuation of the Non-Alcoholic Steatohepatitis Clinical Research Network (NASHU01DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI TONASCIA, JAMES A · 2002 to 2018
$23.2M
San Diego Clinical and Translational Research InstituteUL1TR000100 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S · 2012 to 2015
$19.7M
VEDS Year2-Continuation of the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) Data Coordinating CenterU24DK061730 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI JEANNE M CLARK, David M Shade · 2019 to 2026
$11.3M
Pathogenesis, prognosis, and treatment of NAFLD patientsU01DK061713 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ANNA MAE ELIZABETH DIEHL · 2002 to 2026
$10.3M
Intestinal bacterial metagenome in pediatric NAFLDR01DK088831 · NIDDK · MEDICAL COLLEGE OF WISCONSIN · PI SALZMAN, NITA H, WEINSTOCK, GEORGE M · 2012 to 2016
$7.0M
NCATS NIH HHS UL1 TR000100NCATS NIH HHS UL1 TR001442NIDDK NIH HHS R01 DK088831NIDDK NIH HHS U01 DK061713NIDDK NIH HHS U01 DK061730NIDDK NIH HHS U24 DK061730
6 · The paper itself

Abstract

BACKGROUND &

aimsThe intestinal microbiome might affect the development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD.

methodsWe 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.

resultsFecal 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).

conclusionsIn 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.

Indexed as

Gastrointestinal MicrobiomeAdolescentBacteriaCase-Control StudiesChildCross-Sectional StudiesDNA, BacterialDysbiosisFecesFemaleHost-Pathogen InteractionsHumansIntestinesLiver CirrhosisMaleMetagenomeDNA, BacterialRNA, Ribosomal, 16SFlagellinIntestinal MicrobiotaLipopolysaccharidePediatric

Identifiers

PMID31255652
PMCPMC6756995
OpenAlexW2953761756

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.