Evidence map›Paper›PMID 25614621›Full record

ArticleGut2015

Uncovering effects of antibiotics on the host and microbiota using transkingdom gene networks.

Andrey Morgun, Amiran Dzutsev, Xiaoxi Dong, Renee L Greer, D Joseph Sexton, Jacques Ravel, Martin Schuster, William Hsiao, Polly Matzinger, Natalia Shulzhenko

Open access · greenAbstract read
In one paragraph

Article in Gut, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
158citing papers in PubMed, 2 pooled it
14.0field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

158 citing papers in PubMed, 2 syntheses or guidelines pooled it, 301 citations in OpenAlex.

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  10. Frontiers in microbiology · 2026
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98 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 2 countries.

Andrey MorgunCollege of Pharmacy, Oregon State University, Corvallis, Oregon, USA Ghost Lab, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Amiran DzutsevCancer and Inflammation Program, National Cancer Institute/Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
Xiaoxi DongCollege of Pharmacy, Oregon State University, Corvallis, Oregon, USA.
Renee L GreerCollege of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA.
D Joseph SextonDepartment of Microbiology, Oregon State University, Corvallis, Oregon, USA.
Jacques RavelInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Martin SchusterDepartment of Microbiology, Oregon State University, Corvallis, Oregon, USA.
William HsiaoUniversity of British Columbia, Vancouver, British Columbia, Canada.
Polly MatzingerGhost Lab, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Natalia ShulzhenkoCollege of Veterinary Medicine, Oregon State University, Corvallis, Oregon, USA Ghost Lab, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Oregon State University · USNational Institutes of Health · USNational Cancer Institute · USNational Institute of Allergy and Infectious Diseases · USUniversity of British Columbia · CAUniversity of Maryland, Baltimore · US

Funding

National Gnotobiotic Rodent Resource CenterP40OD010995 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ryan B Sartor · 2012 to 2026
$9.7M
The Danger Model 2: how tissues control ImmunityZIAAI000581 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MATZINGER, POLLY C · 2009 to 2025
$8.5M
The Danger Model And ImmunityZ01AI000581 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI MATZINGER, POLLY C · 1990 to 2008
$6.3M
NATIONAL GNOTOBIOTIC RODENT RESOURCE CENTER: AIDSP40RR018603 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SARTOR, RYAN B · 2004 to 2011
$4.0M
Anti-IL-12p40 Treatment of CVID Enteropathy: Gene Expression/Microbiota AnalysisU01AI109695 · NIAID · OREGON STATE UNIVERSITY · PI MORGUN, ANDRIY · 2013 to 2015
$951k
Intramural NIH HHS Z01 AI000581NCRR NIH HHS P40 RR018603NCRR NIH HHS P40RR018603NIAID NIH HHS U01 AI109695
6 · The paper itself

Abstract

objectiveDespite widespread use of antibiotics for the treatment of life-threatening infections and for research on the role of commensal microbiota, our understanding of their effects on the host is still very limited.

designUsing a popular mouse model of microbiota depletion by a cocktail of antibiotics, we analysed the effects of antibiotics by combining intestinal transcriptome together with metagenomic analysis of the gut microbiota. In order to identify specific microbes and microbial genes that influence the host phenotype in antibiotic-treated mice, we developed and applied analysis of the transkingdom network.

resultsWe found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments.

conclusionsIn addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics.

Indexed as

Gene Regulatory NetworksAnimalsAnti-Bacterial AgentsGastrointestinal MicrobiomeMiceMice, Inbred C57BLAnti-Bacterial AgentsANTIBIOTICSGENE EXPRESSIONMUCOSAL IMMUNITY

Identifiers

PMID25614621
PMCPMC5166700
OpenAlexW2145749857

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.