Evidence map›Paper›PMID 25312952›Full record

ArticleInfection and immunity2015

Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function.

Jhansi L Leslie, Sha Huang, Judith S Opp, Melinda S Nagy, Masayuki Kobayashi, Vincent B Young, Jason R Spence

Open access · bronzeAbstract read
In one paragraph

Article in Infection and immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
210citing 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

210 citing papers in PubMed, 1 synthesis or guideline pooled it, 328 citations in OpenAlex.

  1. Advances in Engineering Human Tissue Models.Frontiers in bioengineering and biotechnology · 2020
    Pooled it
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  9. Attenuation ofJournal of microbiology and biotechnology · 2026
    Article
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  13. Unravelling three-way interactions betweenJournal of medical microbiology · 2025
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150 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

7 authors at 2 institutions in 2 countries.

Jhansi L LeslieDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Sha HuangDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Judith S OppDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Melinda S NagyDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Masayuki KobayashiGraduate School of Bioresource Sciences, Akita Prefectural University, Akita, Japan.
Vincent B YoungDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA Division of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Jason R SpenceDivision of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA Center for Organogenesis, University of Michigan Medical School, Ann Arbor, Michigan, USA spencejr@umich.edu.
University of Michigan–Ann Arbor · USAkita Prefectural University · JP

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
The Interplay Between Host Immunity and Clostridium difficile PathogenesisU19AI090871 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI YOUNG, VINCENT B · 2010 to 2014
$7.5M
Molecular Mechanisms of Microbial Pathogenesis Training ProgramT32AI007528 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CARRUTHERS, VERNON BRUCE · 1998 to 2024
$6.8M
Impacts of Molecular Oxygen on the Structure and Function of the Intestinal MicroR01GM099549 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GRATE, JAY W, SCHMIDT, THOMAS M · 2013 to 2016
$1.1M
Mechanisms of intestine developmentK01DK091415 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SPENCE, JASON · 2011 to 2015
$700k
NIAID NIH HHS 5T32AI007528NIAID NIH HHS T32 AI007528NIAID NIH HHS U19 AI090871NIDDK NIH HHS K01 DK091415NIDDK NIH HHS K01DK091415NIDDK NIH HHS P30 DK034933NIDDK NIH HHS P30DK034933NIGMS NIH HHS R01GM0099549NIGMS NIH HHS R01 GM099549
6 · The paper itself

Abstract

Clostridium difficile is the leading cause of infectious nosocomial diarrhea. The pathogenesis of C. difficile infection (CDI) results from the interactions between the pathogen, intestinal epithelium, host immune system, and gastrointestinal microbiota. Previous studies of the host-pathogen interaction in CDI have utilized either simple cell monolayers or in vivo models. While much has been learned by utilizing these approaches, little is known about the direct interaction of the bacterium with a complex host epithelium. Here, we asked if human intestinal organoids (HIOs), which are derived from pluripotent stem cells and demonstrate small intestinal morphology and physiology, could be used to study the pathogenesis of the obligate anaerobe C. difficile. Vegetative C. difficile, microinjected into the lumen of HIOs, persisted in a viable state for up to 12 h. Upon colonization with C. difficile VPI 10463, the HIO epithelium is markedly disrupted, resulting in the loss of paracellular barrier function. Since similar effects were not observed when HIOs were colonized with the nontoxigenic C. difficile strain F200, we directly tested the role of toxin using TcdA and TcdB purified from VPI 10463. We show that the injection of TcdA replicates the disruption of the epithelial barrier function and structure observed in HIOs colonized with viable C. difficile.

Indexed as

Bacterial ProteinsBacterial ToxinsClostridioides difficileEnterotoxinsHumansIntestinal MucosaOrgan Culture TechniquesOrganoidsBacterial ProteinsBacterial ToxinsEnterotoxinstcdA protein, Clostridium difficiletoxB protein, Clostridium difficile

Identifiers

PMID25312952
PMCPMC4288864
OpenAlexW2152161931

What OpenQuestion holds

Textmetadata
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.