Evidence map›Paper›PMID 28614372›Full record

ArticlePloS one2017

Intestinal organoids model human responses to infection by commensal and Shiga toxin producing Escherichia coli.

Sayali S Karve, Suman Pradhan, Doyle V Ward, Alison A Weiss

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 1 pooled it
12.4field-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

91 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.

  1. Advances in Engineering Human Tissue Models.Frontiers in bioengineering and biotechnology · 2020
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31 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

4 authors at 2 institutions in 1 country.

Sayali S KarveDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, United States of America.
Suman PradhanDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, United States of America.
Doyle V WardCenter for Microbiome Research and Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Alison A WeissDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio, United States of America.ORCID http://orcid.org/0000-0002-4726-8376
University of Cincinnati · USUniversity of Massachusetts Chan Medical School · US

Funding

LCenter for Clinical and Translational Science and TrainingUL1TR001425 · NCATS · UNIVERSITY OF CINCINNATI · PI MEINZEN-DERR, JAREEN, STRAWN, JEFFREY ROBERT · 2015 to 2024
$37.5M
Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI Alexander Miethke · 2007 to 2026
$24.4M
Organoids as a Model System for Studying Gastrointestinal DiseaseU19AI116491 · NIAID · UNIVERSITY OF CINCINNATI · PI MOORE, SEAN RYAN · 2015 to 2019
$4.6M
Glycoconjugate based diagnostics for bacterial toxinsU01AI075498 · NIAID · UNIVERSITY OF CINCINNATI · PI WEISS, ALISON A. · 2007 to 2011
$2.0M
Shiga Toxin Production and Role in PathogenesisR01AI064893 · NIAID · UNIVERSITY OF CINCINNATI · PI WEISS, ALISON A. · 2007 to 2011
$1.9M
Shiga toxin activity in human intestinal organoidsR21AI115003 · NIAID · UNIVERSITY OF CINCINNATI · PI WEISS, ALISON A. · 2016 to 2017
$437k
NCATS NIH HHS UL1 TR001425NIAID NIH HHS R01 AI064893NIAID NIH HHS R21 AI115003NIAID NIH HHS U01 AI075498NIAID NIH HHS U19 AI116491NIDDK NIH HHS P30 DK078392
6 · The paper itself

Abstract

Infection with Shiga toxin (Stx) producing Escherichia coli O157:H7 can cause the potentially fatal complication hemolytic uremic syndrome, and currently only supportive therapy is available. Lack of suitable animal models has hindered study of this disease. Induced human intestinal organoids (iHIOs), generated by in vitro differentiation of pluripotent stem cells, represent differentiated human intestinal tissue. We show that iHIOs with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses. Commensal and O157:H7 introduced into the iHIO lumen replicated rapidly achieving high numbers. Commensal E. coli did not cause damage, and were completely contained within the lumen, suggesting defenses, such as mucus production, can constrain non-pathogenic strains. Some O157:H7 initially co-localized with cellular actin. Loss of actin and epithelial integrity was observed after 4 hours. O157:H7 grew as filaments, consistent with activation of the bacterial SOS stress response. SOS is induced by reactive oxygen species (ROS), and O157:H7 infection increased ROS production. Transcriptional profiling (RNAseq) demonstrated that both commensal and O157:H7 upregulated genes associated with gastrointestinal maturation, while infection with O157:H7 upregulated inflammatory responses, including interleukin 8 (IL-8). IL-8 is associated with neutrophil recruitment, and infection with O157:H7 resulted in recruitment of human neutrophils into the iHIO tissue.

Indexed as

Cells, CulturedCoculture TechniquesEscherichia coliEscherichia coli InfectionsGene Expression ProfilingGene Expression RegulationHumansInduced Pluripotent Stem CellsIntestinesModels, BiologicalNeutrophilsOrganoidsSequence Analysis, RNAShiga-Toxigenic Escherichia coli

Identifiers

PMID28614372
PMCPMC5470682
OpenAlexW2769349519

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.