Evidence map›Paper›PMID 33844988›Full record

ArticleGastroenterology2021

Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection Associates With Functional Alterations in Circulating microRNAs.

Tanya M Monaghan, Anna M Seekatz, Nicholas O Markham, Tung On Yau, Maria Hatziapostolou, Tahseen Jilani, Niki Christodoulou, Brandi Roach, Eleni Birli, Odette Pomenya and 6 more

Open access · greenAbstract readMulticenter Study
In one paragraph

Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 11% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Observational
  7. Review
  8. Review
  9. Journal of bacteriology · 2025
    Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. 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

16 authors at 8 institutions in 3 countries.

Tanya M MonaghanNational Institute for Health Research Nottingham Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom; Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom. Electronic address: tanya.monaghan@nottingham.ac.uk.
Anna M SeekatzDepartment of Biological Sciences, Clemson University, Clemson, South Carolina, USA.
Nicholas O MarkhamDepartment of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Tung On YauDepartment of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Maria HatziapostolouDepartment of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Tahseen JilaniAdvanced Data Analysis Centre, School of Computer Science, University of Nottingham, Nottingham, United Kingdom.
Niki ChristodoulouDepartment of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Brandi RoachDepartment of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Eleni BirliDepartment of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Odette PomenyaDepartment of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom.
Thomas LouieDepartment of Microbiology and infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
D Borden LacyDepartment of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee, USA.
Peter KimDepartment of Mathematics and Statistics, University of Guelph, Ontario, Canada.
Christine LeeVancouver Island Health Authority, Victoria, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Dina KaoDepartment of Medicine, University of Alberta, Edmonton, Alberta, Canada. Electronic address: dkao@ualberta.ca.
Christos PolytarchouDepartment of Biosciences, John van Geest Cancer Research Centre, Centre for Health Aging and Understanding Disease, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom. Electronic address: christos.polytarchou@ntu.ac.uk.
Nottingham Trent University · GBUniversity of Alberta · CAUniversity of Nottingham · GBVanderbilt University · USClemson University · USIsland Health · CAUniversity of Calgary · CAUniversity of Guelph · CA

Funding

Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
TRAINING IN GASTROENTEROLOGYT32DK007673 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 1992 to 2026
$8.4M
Structural mechanisms of Clostridium difficile pathogenesisR01AI095755 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI LACY, DANA BORDEN · 2011 to 2020
$3.9M
Structural Mechanisms of Clostridioides difficile pathogenesisR37AI095755 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Dana Borden Lacy · 2021 to 2026
$3.2M
Critical functions of the gut microbiota that mediate recovery from recurrent Clostridium difficile infectionK01DK111794 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SEEKATZ, ANNA MARIA · 2018 to 2022
$706k
The role of toxins in Clostridium difficile infection pathogenesisI01BX002943 · VA · VETERANS HEALTH ADMINISTRATION · PI LACY, DANA BORDEN · 2016 to 2025
–
BLRD VA I01 BX002943NIAID NIH HHS R01 AI095755NIAID NIH HHS R37 AI095755NIDDK NIH HHS K01 DK111794NIDDK NIH HHS P30 DK058404NIDDK NIH HHS T32 DK007673
6 · The paper itself

Abstract

BACKGROUND AND

aimsThe molecular mechanisms underlying successful fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) remain poorly understood. The primary objective of this study was to characterize alterations in microRNAs (miRs) following FMT for rCDI.

methodsSera from 2 prospective multicenter randomized controlled trials were analyzed for miRNA levels with the use of the Nanostring nCounter platform and quantitative reverse-transcription (RT) polymerase chain reaction (PCR). In addition, rCDI-FMT and toxin-treated animals and ex vivo human colonoids were used to compare intestinal tissue and circulating miRs. miR inflammatory gene targets in colonic epithelial and peripheral blood mononuclear cells were evaluated by quantitative PCR (qPCR) and 3'UTR reporter assays. Colonic epithelial cells were used for mechanistic, cytoskeleton, cell growth, and apoptosis studies.

resultsmiRNA profiling revealed up-regulation of 64 circulating miRs 4 and 12 weeks after FMT compared with screening, of which the top 6 were validated in the discovery cohort by means of RT-qPCR. In a murine model of relapsing-CDI, RT-qPCR analyses of sera and cecal RNA extracts demonstrated suppression of these miRs, an effect reversed by FMT. In mouse colon and human colonoids, C difficile toxin B (TcdB) mediated the suppressive effects of CDI on miRs. CDI dysregulated DROSHA, an effect reversed by FMT. Correlation analyses, qPCR ,and 3'UTR reporter assays revealed that miR-23a, miR-150, miR-26b, and miR-28 target directly the 3'UTRs of IL12B, IL18, FGF21, and TNFRSF9, respectively. miR-23a and miR-150 demonstrated cytoprotective effects against TcdB.

conclusionsThese results provide novel and provocative evidence that modulation of the gut microbiome via FMT induces alterations in circulating and intestinal tissue miRs. These findings contribute to a greater understanding of the molecular mechanisms underlying FMT and identify new potential targets for therapeutic intervention in rCDI.

Indexed as

Fecal Microbiota TransplantationGastrointestinal MicrobiomeReinfectionAdultAgedAged, 80 and overAnimalsCirculating MicroRNAClostridium InfectionsDisease Models, AnimalFemaleHumansIntestinesMaleMiddle AgedRandomized Controlled Trials as TopicCirculating MicroRNAC difficileDROSHAFecal TransplantationmicroRNA

Identifiers

PMID33844988
PMCPMC8579492
OpenAlexW3154757085

What OpenQuestion holds

Textmetadata
LicenceTDM
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.