Evidence map›Paper›PMID 27329502›Full record

ArticleJournal of gastroenterology2017

A human gut ecosystem protects against C. difficile disease by targeting TcdA.

Sarah Lynn Martz, Mabel Guzman-Rodriguez, Shu-Mei He, Curtis Noordhof, David John Hurlbut, Gregory Brian Gloor, Christian Carlucci, Scott Weese, Emma Allen-Vercoe, Jun Sun and 2 more

Open access · greenAbstract read
In one paragraph

Article in Journal of gastroenterology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

14 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Gut microbiota-specific IgAScience immunology · 2020
    Observational
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Treatment of recurrentGastroenterology report · 2018
    Review
  14. Control ofMicrobiology spectrum · 2017
    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

12 authors at 6 institutions in 2 countries.

Sarah Lynn MartzDivision of Infectious Diseases/GI Diseases Research Unit Wing, Department of Medicine, Kingston General Hospital, Queen's University, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada.
Mabel Guzman-RodriguezDivision of Infectious Diseases/GI Diseases Research Unit Wing, Department of Medicine, Kingston General Hospital, Queen's University, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada.
Shu-Mei HeDivision of Infectious Diseases/GI Diseases Research Unit Wing, Department of Medicine, Kingston General Hospital, Queen's University, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada.
Curtis NoordhofDivision of Infectious Diseases/GI Diseases Research Unit Wing, Department of Medicine, Kingston General Hospital, Queen's University, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada.
David John HurlbutDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, K7L 2V7, Canada.
Gregory Brian GloorDepartment of Biochemistry, University of Western Ontario, London, ON, N6A 5C1, Canada.
Christian CarlucciDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
Scott WeeseDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
Emma Allen-VercoeDepartment of Molecular and Cellular Biology, University of Guelph, Guelph, ON, N1G 2W1, Canada.
Jun SunDivision of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Erika Chiong ClaudDepartments of Pediatrics and Medicine, University of Chicago, Chicago, IL, 60637, USA.
Elaine Olga PetrofDivision of Infectious Diseases/GI Diseases Research Unit Wing, Department of Medicine, Kingston General Hospital, Queen's University, 76 Stuart Street, Kingston, ON, K7L 2V7, Canada. eop@queensu.ca.
Queen's University · CAUniversity of Guelph · CAKingston General Hospital · CAUniversity of Chicago · USUniversity of Illinois Chicago · USWestern University · CA

Funding

Vitamin D Receptor Regulation of Microbiota in Intestinal EpitheliaR01DK105118 · NIDDK · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SUN, JUN · 2016 to 2020
$1.8M
Microbes that Matter: defining optimal formulations for Microbial Ecosystem TherapeuticsR33AI121575 · NIAID · QUEEN'S UNIVERSITY AT KINGSTON · PI ALLEN-VERCOE, EMMA, SHETH, PRAMEET · 2018 to 2020
$928k
Microbes that Matter: defining optimal formulations for Microbial Ecosystem TherapeuticsR21AI121575 · NIAID · QUEEN'S UNIVERSITY AT KINGSTON · PI ALLEN-VERCOE, EMMA, PETROF, ELAINE O · 2016 to 2017
$297k
NIAID NIH HHS R21 AI121575NIAID NIH HHS R33 AI121575NIDDK NIH HHS R01 DK105118
6 · The paper itself

Abstract

backgroundA defined Microbial Ecosystem Therapeutic (MET-1, or "RePOOPulate") derived from the feces of a healthy volunteer can cure recurrent C. difficile infection (rCDI) in humans. The mechanisms of action whereby healthy microbiota protect against rCDI remain unclear. Since C. difficile toxins are largely responsible for the disease pathology of CDI, we hypothesized that MET-1 exerts its protective effects by inhibiting the effects of these toxins on the host.

methodsA combination of in vivo (antibiotic-associated mouse model of C. difficile colitis, mouse ileal loop model) and in vitro models (FITC-phalloidin staining, F actin Western blots and apoptosis assay in Caco2 cells, transepithelial electrical resistance measurements in T84 cells) were employed.

resultsMET-1 decreased both local and systemic inflammation in infection and decreased both the cytotoxicity and the amount of TcdA detected in stool, without an effect on C. difficile viability. MET-1 protected against TcdA-mediated damage in a murine ileal loop model. MET-1 protected the integrity of the cytoskeleton in cells treated with purified TcdA, as indicated by FITC-phalloidin staining, F:G actin assays and preservation of transepithelial electrical resistance. Finally, co-incubation of MET-1 with purified TcdA resulted in decreased detectable TcdA by Western blot analysis.

conclusionsMET-1 intestinal microbiota confers protection against C. difficile and decreases C. difficile-mediated inflammation through its protective effects against C. difficile toxins, including enhancement of host barrier function and degradation of TcdA. The effect of MET-1 on C. difficile viability seems to offer little, if any, contribution to its protective effects on the host.

Indexed as

Gastrointestinal MicrobiomeAnimalsBacterial ToxinsBiological TherapyCaco-2 CellsClostridioides difficileCytoskeletonDisease Models, AnimalEnterocolitis, PseudomembranousEnterotoxinsFecesFibroblastsHumansMice, Inbred C57BLBacterial ToxinsEnterotoxinstcdA protein, Clostridium difficileC. difficileMicrobiotaTcdA

Identifiers

PMID27329502
PMCPMC5177537
OpenAlexW2472022910

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.