Evidence map›Paper›PMID 26261005›Full record

ArticleGastroenterology2015

Increased Expression of DUOX2 Is an Epithelial Response to Mucosal Dysbiosis Required for Immune Homeostasis in Mouse Intestine.

Helmut Grasberger, Jun Gao, Hiroko Nagao-Kitamoto, Sho Kitamoto, Min Zhang, Nobuhiko Kamada, Kathryn A Eaton, Mohamad El-Zaatari, Andrew B Shreiner, Juanita L Merchant and 2 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 96 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 1 pooled it
5.0field-weighted citation impact, top 4% 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

96 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.

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  18. De novo DUOX2 expression in neutrophil subsets shapes the pathogenesis of intestinal disease.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Review
  20. Article

36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Helmut GrasbergerDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan. Electronic address: helmut@umich.edu.
Jun GaoDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Hiroko Nagao-KitamotoDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Sho KitamotoDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Min ZhangDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Nobuhiko KamadaDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Kathryn A EatonUnit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Mohamad El-ZaatariDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Andrew B ShreinerDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Juanita L MerchantDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
Chung OwyangDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
John Y KaoDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan. Electronic address: jykao@med.umich.edu.
University of Michigan–Ann Arbor · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Mechanisms of Gastrointestional Growth &TransformationR01DK055732 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MERCHANT, JUANITA L. · 2000 to 2014
$4.1M
Training in Basic and Translational Digestive SciencesT32DK094775 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI JOHN Y KAO, LINDA C. SAMUELSON · 2012 to 2026
$3.6M
Role of Dendritic Cells in H pylori-induced Treg-mediated Host Immune ToleranceR01DK087708 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KAO, JOHN Y · 2011 to 2015
$2.0M
Modulation of Visceral Hypersensitivity in IBS by Lipid MediatorsR01DK110436 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GRABAUSKAS, GINTAUTAS, OWYANG, CHUNG · 2016 to 2019
$1.7M
NIDDK NIH HHS 5P30DK034933NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK055732NIDDK NIH HHS R01DK055732-15NIDDK NIH HHS R01 DK087708NIDDK NIH HHS R01DK087708-01NIDDK NIH HHS R01 DK110436NIDDK NIH HHS T32 DK094775
6 · The paper itself

Abstract

BACKGROUND &

aimsDual oxidase 2 (DUOX2), a hydrogen-peroxide generator at the apical membrane of gastrointestinal epithelia, is up-regulated in patients with inflammatory bowel disease (IBD) before the onset of inflammation, but little is known about its effects. We investigated the role of DUOX2 in maintaining mucosal immune homeostasis in mice.

methodsWe analyzed the regulation of DUOX2 in intestinal tissues of germ-free vs conventional mice, mice given antibiotics or colonized with only segmented filamentous bacteria, mice associated with human microbiota, and mice with deficiencies in interleukin (IL) 23 and IL22 signaling. We performed 16S ribosomal RNA gene quantitative polymerase chain reaction of intestinal mucosa and mesenteric lymph nodes of Duoxa(-/-) mice that lack functional DUOX enzymes. Genes differentially expressed in Duoxa(-/-) mice compared with co-housed wild-type littermates were correlated with gene expression changes in early-stage IBD using gene set enrichment analysis.

resultsColonization of mice with segmented filamentous bacteria up-regulated intestinal expression of DUOX2. DUOX2 regulated redox signaling within mucosa-associated microbes and restricted bacterial access to lymphatic tissues of the mice, thereby reducing microbiota-induced immune responses. Induction of Duox2 transcription by microbial colonization did not require the mucosal cytokines IL17 or IL22, although IL22 increased expression of Duox2. Dysbiotic, but not healthy human microbiota, activated a DUOX2 response in recipient germ-free mice that corresponded to abnormal colonization of the mucosa with distinct populations of microbes. In Duoxa(-/-) mice, abnormalities in ileal mucosal gene expression at homeostasis recapitulated those in patients with mucosal dysbiosis.

conclusionsDUOX2 regulates interactions between the intestinal microbiota and the mucosa to maintain immune homeostasis in mice. Mucosal dysbiosis leads to increased expression of DUOX2, which might be a marker of perturbed mucosal homeostasis in patients with early-stage IBD.

Indexed as

DysbiosisImmunity, MucosalAnimalsAnti-Bacterial AgentsBacteriaBacterial TranslocationDisease Models, AnimalDual OxidasesEnzyme InductionEpithelial CellsFecesFemaleGastroenteritisHost-Pathogen InteractionsHumansInflammatory Bowel DiseasesAnti-Bacterial AgentsDual OxidasesDuox1 protein, mouseDUOX2 protein, humanInterleukin-22interleukin-23 receptor, mouseInterleukinsNADPH OxidasesReceptors, InterleukinGastroenterologyInflammatory Bowel DiseaseIntestineMicrobial Dysbiosis

Identifiers

PMID26261005
PMCPMC4663159
OpenAlexW1059125197

What OpenQuestion holds

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Registered trials

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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.