Evidence map›Paper›PMID 30626868›Full record

ArticleNature communications2019

Enhancement of the gut barrier integrity by a microbial metabolite through the Nrf2 pathway.

Rajbir Singh, Sandeep Chandrashekharappa, Sobha R Bodduluri, Becca V Baby, Bindu Hegde, Niranjan G Kotla, Ankita A Hiwale, Taslimarif Saiyed, Paresh Patel, Matam Vijay-Kumar and 11 more

Abstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 372 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
372citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

372 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  9. Targeting PKGIα CysScience advances · 2026
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312 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Rajbir SinghDepartment of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
Sandeep ChandrashekharappaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India.
Sobha R BodduluriDepartment of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
Becca V BabyDepartment of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
Bindu HegdeDepartment of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
Niranjan G KotlaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India.
Ankita A HiwaleInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India.
Taslimarif SaiyedCentre for Cellular and Molecular Platforms (C-CAMP), GKVK campus, Bangalore, Karnataka, 560065, India.
Paresh PatelCentre for Cellular and Molecular Platforms (C-CAMP), GKVK campus, Bangalore, Karnataka, 560065, India.
Matam Vijay-KumarDepartment of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA.
Morgan G I LangilleDepartment of Pharmacology, Dalhousie University, Halifax, B3H 4R2, Nova Scotia, Canada.
Gavin M DouglasDepartment of Pharmacology, Dalhousie University, Halifax, B3H 4R2, Nova Scotia, Canada.
Xi ChengDepartment of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, 43614, USA.ORCID http://orcid.org/0000-0002-0838-5094
Eric C RouchkaComputer Engineering and Computer Science, Kentucky Biomedical Research Infrastructure Network, University of Louisville, Louisville, KY, 40202, USA.ORCID http://orcid.org/0000-0003-3487-6572
Sabine J WaigelDepartment of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Gerald W DrydenDepartment of Medicine, University of Louisville, Louisville, KY, 40202, USA.
Houda AlatassiDepartment of Pathology, University of Louisville, Louisville, KY, 40202, USA.
Huang-Ge ZhangDepartment of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
Bodduluri HaribabuDepartment of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA.
Praveen K VemulaInstitute for Stem Cell Biology and Regenerative Medicine (inStem), GKVK campus, Bangalore, Karnataka, 560065, India. praveenv@instem.res.in.ORCID http://orcid.org/0000-0003-0279-4230
Venkatakrishna R JalaDepartment of Microbiology and Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, 40202, USA. jvrao001@louisville.edu.

Funding

WKU Lead Faculty AwardP20GM103436 · NIGMS · UNIVERSITY OF LOUISVILLE · PI ERIC C ROUCHKA · 2012 to 2026
$60.1M
Understanding the Host-Microbiome-Therapeutic Triad: Implications for Designing Alternative IntravaginalP20GM125504 · NIGMS · UNIVERSITY OF LOUISVILLE · PI James Tristan Collins · 2018 to 2026
$24.4M
PILOT PROJECT PROGRAMP30GM106396 · NIGMS · UNIVERSITY OF LOUISVILLE · PI EATON, JOHN W · 2013 to 2017
$5.4M
PQ-10: Microbial metabolite, Urolithin A is a potent immunomodulator and chemosensitizing adjuvant in treating colon cancer.R21CA216090 · NCI · UNIVERSITY OF LOUISVILLE · PI JALA, VENKATAKRISHNA RAO · 2017 to 2018
$368k
CCR2 mediated inflammation and gut microbiota in promoting intestinal cancerR21CA191683 · NCI · UNIVERSITY OF LOUISVILLE · PI JALA, VENKATAKRISHNA RAO · 2015 to 2016
$359k
NCI NIH HHS R21 CA191683NCI NIH HHS R21 CA216090NIGMS NIH HHS P20 GM103436NIGMS NIH HHS P20 GM125504NIGMS NIH HHS P30 GM106396NIH HHS P20GM125504-01NIH HHS R21CA216090
6 · The paper itself

Abstract

The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier function and inhibit unwarranted inflammation. We demonstrate that UroA and UAS03 exert their barrier functions through activation of aryl hydrocarbon receptor (AhR)- nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent pathways to upregulate epithelial tight junction proteins. Importantly, treatment with these compounds attenuated colitis in pre-clinical models by remedying barrier dysfunction in addition to anti-inflammatory activities. Cumulatively, the results highlight how microbial metabolites provide two-pronged beneficial activities at gut epithelium by enhancing barrier functions and reducing inflammation to protect from colonic diseases.

Indexed as

AnimalsBasic Helix-Loop-Helix ProteinsCaco-2 CellsCoumarinsEpithelial CellsGene Expression RegulationHT29 CellsHumansIntestinal MucosaMacrophagesMiceMice, Inbred C57BLMice, KnockoutNF-E2-Related Factor 2Receptors, Aryl HydrocarbonSpecific Pathogen-Free Organisms3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-oneAhr protein, mouseBasic Helix-Loop-Helix ProteinsCoumarinsNFE2L2 protein, humanNfe2l2 protein, mouseNF-E2-Related Factor 2Receptors, Aryl HydrocarbonTight Junction Proteins

Identifiers

PMID30626868
PMCPMC6327034

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.