Evidence map›Paper›PMID 38267224›Full record

ArticleJournal of Crohn's & colitis2024

Toxigenic Clostridium perfringens Isolated from At-Risk Paediatric Inflammatory Bowel Disease Patients.

James Kuo, Jasmina Uzunovic, Amanda Jacobson, Michelle Dourado, Sarah Gierke, Manohary Rajendram, Daniela Keilberg, Jordan Mar, Emily Stekol, Joanna Curry and 13 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of Crohn's & colitis, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

10 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 1 institution in 1 country.

James KuoDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.
Jasmina UzunovicDepartment of Bioinformatics, Genentech Inc., South San Francisco, CA, USA.
Amanda JacobsonDepartment of Immunology Discovery, Genentech Inc., South San Francisco, CA, USA.
Michelle DouradoDepartment of Neuroscience, Genentech Inc., South San Francisco, CA, USA.
Sarah GierkeDepartment of Pathology, Genentech Inc., South San Francisco, CA, USA.
Manohary RajendramDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.
Daniela KeilbergDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.
Jordan MarDepartment of Human Pathobiology and OMNI Reverse Translation, Genentech Inc., South San Francisco, CA, USA.
Emily StekolDepartment of Pediatrics, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, 94158, USA.
Joanna CurryDepartment of Pediatrics, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, 94158, USA.
Sofia VerstraeteDepartment of Pediatrics, University of California San Francisco Benioff Children's Hospital, San Francisco, CA, 94158, USA.
Jessica LundDepartment of Microchemistry, Proteomics & Lipidomics, Genentech Inc., South San Francisco, CA, USA.
Yuxin LiangDepartment of Microchemistry, Proteomics & Lipidomics, Genentech Inc., South San Francisco, CA, USA.
Fiona B TamburiniDepartment of Human Pathobiology and OMNI Reverse Translation, Genentech Inc., South San Francisco, CA, USA.
Natalie S OmattageDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.
Matthieu MasureelDepartment of Structural Biology, Genentech Inc., South San Francisco, CA, USA.
Steven T RutherfordDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.
David H HackosDepartment of Neuroscience, Genentech Inc., South San Francisco, CA, USA.
Man-Wah TanDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.
Allyson L ByrdDepartment of Cancer Immunology, Genentech Inc., South San Francisco, CA, USA.
Mary E KeirDepartment of Human Pathobiology and OMNI Reverse Translation, Genentech Inc., South San Francisco, CA, USA.
Elizabeth SkippingtonDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.
Kelly M StorekDepartment of Infectious Diseases and Host-Microbe Interactions, Genentech Inc., South San Francisco, CA, USA.ORCID 0000-0002-2289-0214
University of California, San Francisco · US

Funding

Genentech
6 · The paper itself

Abstract

BACKGROUND AND

aimsThis study aimed to identify microbial drivers of inflammatory bowel disease [IBD], by investigating mucosal-associated bacteria and their detrimental products in IBD patients.

methodsWe directly cultured bacterial communities from mucosal biopsies from paediatric gastrointestinal patients and examined for pathogenicity-associated traits. Upon identifying Clostridium perfringens as toxigenic bacteria present in mucosal biopsies, we isolated strains and further characterized toxicity and prevalence.

resultsMucosal biopsy microbial composition differed from corresponding stool samples. C. perfringens was present in eight of nine patients' mucosal biopsies, correlating with haemolytic activity, but was not present in all corresponding stool samples. Large IBD datasets showed higher C. perfringens prevalence in stool samples of IBD adults [18.7-27.1%] versus healthy controls [5.1%]. In vitro, C. perfringens supernatants were toxic to cell types beneath the intestinal epithelial barrier, including endothelial cells, neuroblasts, and neutrophils, while the impact on epithelial cells was less pronounced, suggesting C. perfringens may be particularly damaging when barrier integrity is compromised. Further characterization using purified toxins and genetic insertion mutants confirmed perfringolysin O [PFO] toxin was sufficient for toxicity. Toxin RNA signatures were found in the original patient biopsies by PCR, suggesting intestinal production. C. perfringens supernatants also induced activation of neuroblast and dorsal root ganglion neurons in vitro, suggesting C. perfringens in inflamed mucosal tissue may directly contribute to abdominal pain, a frequent IBD symptom.

conclusionsGastrointestinal carriage of certain toxigenic C. perfringens may have an important pathogenic impact on IBD patients. These findings support routine monitoring of C. perfringens and PFO toxins and potential treatment in patients.

Indexed as

Bacterial ToxinsClostridium perfringensFecesInflammatory Bowel DiseasesIntestinal MucosaAdolescentBiopsyChildClostridium InfectionsFemaleHemolysin ProteinsHumansMaleBacterial ToxinsClostridium perfringens theta-toxinHemolysin ProteinsbiopsyClostridioides difficileMicrobiomemucosa

Identifiers

PMID38267224
PMCPMC11302968
OpenAlexW4391187681

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.