Evidence map›Paper›PMID 29988118›Full record

ArticleMucosal immunology2018

Inflammation-independent TL1A-mediated intestinal fibrosis is dependent on the gut microbiome.

Noam Jacob, Jonathan P Jacobs, Kotaro Kumagai, Connie W Y Ha, Yoshitake Kanazawa, Venu Lagishetty, Katherine Altmayer, Ariel M Hamill, Aimee Von Arx, R Balfour Sartor and 5 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Mucosal immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
6.9field-weighted citation impact, top 3% 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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. TL1A Inhibition in Inflammatory Bowel Disease: A Pipeline Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review

6 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

15 authors at 3 institutions in 1 country.

Noam JacobF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. njacob@mednet.ucla.edu.
Jonathan P JacobsVatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Kotaro KumagaiF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Connie W Y HaF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Yoshitake KanazawaF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Venu LagishettyVatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Katherine AltmayerF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Ariel M HamillF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Aimee Von ArxF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
R Balfour SartorDepartments of Medicine, Microbiology and Immunology and National Gnotobiotic Rodent Resource Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
Suzanne DevkotaF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Jonathan BraunDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Kathrin S MichelsenF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Stephan R TarganF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
David Q ShihF. Widjaja Foundation, Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. david10021@gmail.com.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · USUniversity of North Carolina at Chapel Hill · US

Funding

Using polygenic scores to enhance both variant discovery, and understanding of functional consequences of genetic variation in IBD.P01DK046763 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI TARGAN, STEPHAN R. · 1992 to 2020
$31.1M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Role of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SHEIKH, SHEHZAD Z. · 2013 to 2023
$17.9M
GASTROENTEROLOGYT32DK007180 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JENSEN, DENNIS MICHAEL · 1986 to 2025
$10.0M
National Gnotobiotic Rodent Resource CenterP40OD010995 · OD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Ryan B Sartor · 2012 to 2026
$9.7M
TNF ALPHA AND CROHNS DISEASE MUCOSAL INFLAMMATIONR01DK056328 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI TARGAN, STEPHAN R. · 1999 to 2018
$6.9M
The Roles of IBD Associated Genes ATG16L1 and TNFSF15 in Gut Mucosal InflammationK08DK093578 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI SHIH, DAVID Q. · 2012 to 2016
$755k
NIDDK NIH HHS K08 DK093578NIDDK NIH HHS L30 DK110927NIDDK NIH HHS P01 DK046763NIDDK NIH HHS P01 DK094779NIDDK NIH HHS P30 DK034987NIDDK NIH HHS P30 DK041301NIDDK NIH HHS R01 DK056328NIDDK NIH HHS T32 DK007180NIH HHS P40 OD010995
6 · The paper itself

Abstract

Tumor necrosis factor-like cytokine 1A (TL1A, TNFSF15) is implicated in inflammatory bowel disease (IBD), modulating the location and severity of intestinal inflammation and fibrosis. TL1A expression is increased in inflamed gut mucosa and associated with fibrostenosing Crohn's disease. Tl1a-overexpression in mice lead to spontaneous ileitis, and exacerbated induced proximal colitis and fibrosis. IBD is associated with shifts in the gut microbiome, but the effect of differing microbial populations and their interaction with TL1A on fibrosis has not been investigated. We demonstrate that the pro-fibrotic and inflammatory phenotype resulting from Tl1a-overexpression is abrogated in the absence of resident microbiota. To evaluate if this is due to the absence of a unique bacterial population, as opposed to any bacteria per se, we gavaged germ-free (GF) wild-type and Tl1a-transgenic (Tl1a-Tg) mice with stool from specific pathogen free (SPF) mice and a healthy human donor (Hu). Reconstitution with SPF, but not Hu microbiota, resulted in increased intestinal collagen deposition and fibroblast activation in Tl1a-Tg mice. Notably, there was reduced fibroblast migration and activation under GF conditions compared to native conditions. We then identified several candidate organisms that correlated directly with increased fibrosis in reconstituted mice and showed that these organisms directly impact fibroblast function in vitro. Thus, Tl1a-mediated intestinal fibrosis and fibroblast activation are dependent on specific microbial populations.

Indexed as

AnimalsColitisCollagenCrohn DiseaseFibroblastsFibrosisGastrointestinal MicrobiomeHumansIleitisInflammationInflammatory Bowel DiseasesIntestinal MucosaIntestinesMiceMice, Inbred C57BLMice, TransgenicCollagenTnfsf15 protein, mouseTumor Necrosis Factor Ligand Superfamily Member 15

Identifiers

PMID29988118
PMCPMC6162160
OpenAlexW2863875449

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.