Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 9 February 2021
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Loomba R, Seguritan V, Li W, Long T, Klitgord N, Bhatt A, Dulai PS, Caussy C, Bettencourt R, Highlander SK, Jones MB, Sirlin CB, Schnabl B, Brinkac L, Schork N, Chen CH, Brenner DA, Biggs W, Yooseph S, Venter JC, Nelson KE
Journal
Cell metabolism
Year
2017
The presence of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is the most important predictor of liver mortality. There are limited data on the diagnostic accuracy of gut microbiota-derived signature for predicting the presence of advanced fibrosis. In this prospective study, we characterized the gut microbiome compositions using whole-genome shotgun sequencing of DNA extracted from stool samples. This study included 86 uniquely well-characterized patients with biopsy-proven NAFLD, of which 72 had mild/moderate (stage 0-2 fibrosis) NAFLD, and 14 had advanced fibrosis (stage 3 or 4 fibrosis). We identified a set of 40 features (p < 0.006), which included 37 bacterial species that were used to construct a Random Forest classifier model to distinguish mild/moderate NAFLD from advanced fibrosis. The model had a robust diagnostic accuracy (AUC 0.936) for detecting advanced fibrosis. This study provides preliminary evidence for a fecal-microbiome-derived metagenomic signature to detect advanced fibrosis in NAFLD.

Experiment 1


Reviewed Marked as Reviewed by Shaimaa Elsafoury on 9 February 2021

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743, Lwaldron

Subjects

Location of subjects
United States of America
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
mild/moderate fibrosis
Group 1 name Corresponds to the case (exposed) group for case-control studies
advanced fibrosis
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Based on clinical, magnetic resonance, histology assessment; Mild/Moderate NAFLD: fibrosis 0-2. Advanced NAFLD: fibrosis 3-4
Group 0 sample size Number of subjects in the control (unexposed) group
72
Group 1 sample size Number of subjects in the case (exposed) group
14

Lab analysis

Sequencing type
WMS
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Random Forest Analysis
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
"Shannon diversity" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values for the "Matched on" property.Shannon diversity
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index


Signature 1

Reviewed Marked as Reviewed by Fatima on 28 July 2021

Curated date: 2021/01/10

Curator: Shaimaa Elsafoury

Revision editor(s): Lwaldron, WikiWorks743

Source: Table 3

Description: relative abundances of top 4 phyla found in all samples and representative species from the first 3 phyla.

Abundance in Group 1: decreased abundance in advanced fibrosis

NCBI Links
Blautia obeum
[Eubacterium] rectale

Revision editor(s): Lwaldron, WikiWorks743