Evidence map›Paper›PMID 32034605›Full record

ArticleDigestive diseases and sciences2021

Reversal of Pathogen-Induced Barrier Defects in Intestinal Epithelial Cells by Contra-pathogenicity Agents.

Naheed Choudhry, Flora Scott, Meghan Edgar, Gareth J Sanger, Paul Kelly

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Article in Digestive diseases and sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
0.3field-weighted citation impact, top 30% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
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  11. Strategies for Zinc Uptake inFrontiers in microbiology · 2021
    Review
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

5 authors at 2 institutions in 2 countries.

Naheed ChoudhryBarts and The London School of Medicine, Queen Mary, University of London, London, E1 2AT, UK. n.choudhry@qmul.ac.uk.ORCID 0000-0001-6386-9908
Flora ScottBarts and The London School of Medicine, Queen Mary, University of London, London, E1 2AT, UK.
Meghan EdgarGastroenterology Drug Discovery Unit, Takeda California, Inc., 10410 Science Center Drive, San Diego, CA, 92121, USA.
Gareth J SangerBarts and The London School of Medicine, Queen Mary, University of London, London, E1 2AT, UK.
Paul KellyBarts and The London School of Medicine, Queen Mary, University of London, London, E1 2AT, UK.
Queen Mary University of London · GBTakeda (United States) · US

Funding

Medical Research Council G0900805
6 · The paper itself

Abstract

backgroundEnvironmental enteropathy (EE) is associated with stunting, impairment of responses to oral vaccines, and other adverse health consequences in young children throughout the developing world. EE is characterized by chronic low-grade intestinal inflammation and disrupted epithelial barrier integrity, partly resulting from dysregulation of tight junction proteins, observed in other enteropathies such as celiac disease. During EE, this dysregulation of tight junction expression amplifies translocation of pathogenic bacteria across the intestinal mucosa.

aimsThe aim was to determine whether enteropathogen-mediated epithelial barrier failure can be ameliorated using contra-pathogenicity therapies.

methodsIntestinal epithelial barrier damage was assessed in Caco-2 cells incubated with three important enteropathogens identified in EE patients: Enteropathogenic Escherichia coli (EPEC), Citrobacter rodentium (C. rodentium), and Cryptosporidium parvum (C. parvum). Potential therapeutic molecules were tested to detect effects on transepithelial resistance (TER), bacterial translocation (BT), claudin-4 expression, and regulation of the inflammatory cytokine response.

resultsAll three enteropathogens compared to uninfected cells, reduced TER (EPEC; p < 0.0001, C. rodentium; p < 0.0001, C. parvum; p < 0.0007), reduced claudin-4 expression, and permitted BT (EPEC; p < 0.0001, C. rodentium; p < 0.0001, C. parvum; p < 0.0003) through the monolayer. Zinc, colostrum, epidermal growth factor, trefoil factor 3, resistin-like molecule-β, hydrocortisone, and the myosin light chain kinase inhibitor ML7 (Hexahydro-1-[(5-iodo-1-naphthalenyl)sulfonyl]-1H-1,4-diazepine hydrochloride); ML7) improved TER (up to 70%) and decreased BT (as much as 96%). Only zinc demonstrated modest antimicrobial activity.

conclusionThe enteropathogens impaired intestinal-epithelial barrier integrity with dysregulation of claudin-4 and increased bacterial translocation. Enteropathogen-mediated damage was reduced using contra-pathogenicity agents which mitigated the effects of pathogens without direct antimicrobial activity.

Indexed as

Bacterial TranslocationCaco-2 CellsCitrobacter rodentiumCryptosporidium parvumEnteropathogenic Escherichia coliEpidermal Growth FactorEpithelial CellsHumansHydrocortisoneIntestinal DiseasesIntestinal MucosaTransendothelial and Transepithelial MigrationEpidermal Growth FactorHydrocortisoneCitrobacter rodentiumClaudin-4Cryptosporidium parvumEnteropathogenic Escherichia coliIntestinal barrierMicrobial translocation

Identifiers

PMID32034605
OpenAlexW3004690005

What OpenQuestion holds

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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.