Evidence map›Paper›PMID 42378712›Full record

ArticleJournal of Crohn's & colitis2026

Multiomics analysis dissects the molecular foundation of perianal fistulas associated with Crohn's disease and of cryptoglandular origin.

Céline Mamie, Daniela Cabalzar-Wondberg, Matthias Turina, Marcin Wawrzyniak, Benjamin Misselwitz, Nicola Zamboni, Claudia Gottier, Silvia Lang, Gerhard Rogler, Alvaro Avivar-Valderas and 5 more

Abstract read
In one paragraph

Article in Journal of Crohn's & colitis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Céline MamieDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.ORCID 0000-0003-1415-6674
Daniela Cabalzar-WondbergDepartment of Visceral and Transplant Surgery, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Matthias TurinaDepartment of Visceral and Transplant Surgery, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Marcin WawrzyniakDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Benjamin MisselwitzDepartment of Medicine II, University Hospital LMU Munich, Munich 80539, Germany.
Nicola ZamboniInstitute of Molecular Systems Biology, ETH Zurich, Zurich 8093, Switzerland.
Claudia GottierDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Silvia LangDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Gerhard RoglerDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Alvaro Avivar-ValderasCell Therapy Technology Sciences, Takeda Cell Therapy Technology Center (Tigenix SAU), Madrid 28760, Spain.
Olga de la RosaCell Therapy Technology Sciences, Takeda Cell Therapy Technology Center (Tigenix SAU), Madrid 28760, Spain.
Ninfa CandelaTakeda Development Center Americas (TDCA), Takeda Development Center Americas, Inc, Cambridge, MA 02142, United States.ORCID 0000-0003-3469-6088
Jay TangTakeda Development Center Americas (TDCA), Takeda Development Center Americas, Inc, Cambridge, MA 02142, United States.
Yasser MorsyDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.
Michael ScharlDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland.

Funding

Takeda Pharmaceutical Company Ltd
6 · The paper itself

Abstract

BACKGROUND AND

objectivePerianal fistulas, either of cryptoglandular origin (CgF) or associated with Crohn's disease (CDF), have limited treatment options and pose a tremendous burden for affected patients. We recently showed that the epithelial-mesenchymal transition (EMT) contributes to CDF pathogenesis, but detailed mechanisms need further evaluation. Here, we performed multiomics analysis to gain further molecular insights into fistula pathogenesis.

designRectal biopsies, swabs, fistula curettage, and serum samples were derived from patients with either CDF (n = 23) or CgF (n = 17) and analyzed by bulk RNA sequencing, metagenomics, untargeted metabolomics, or multiplex-ELISA, where appropriate.

resultsTranscriptomics revealed striking differences in gene expression between rectal mucosa and fistula tract samples. However, the transcriptomes of CDF and CgF were comparable, and genes involved in EMT, inflammation and tumor necrosis factor signaling were prominent in both fistula types. A set of 18 genes was found to be differentially expressed in CDF and CgF and might allow discrimination. The overall microbiome composition within fistula tracts did not differ between CDF and CgF patients, but there was a significant difference in rectal microbiome compositions. On a species level, we detected an enrichment of disease-specific, pathogenic species in the fistula tracts. Of note, Bacteroides ssp., Fusobacterium animalis, and Staphylococcus aureus prevailed within CDF.

conclusionOur data demonstrate only minor differences in the transcriptome and the microbiome between CDF and CgF, but clear differences when compared to rectal mucosa biopsies. Thus, our data suggest that the molecular makeup underlying the pathophysiology of fistulas might be comparable between CDF and CgF.

Indexed as

Crohn DiseaseRectal FistulaAdultEpithelial-Mesenchymal TransitionFemaleGastrointestinal MicrobiomeGene Expression ProfilingHumansIntestinal MucosaMaleMetabolomicsMiddle AgedMultiomicsTranscriptomebasic scienceexperimental models and pathophysiologymicrobiology

Identifiers

PMID42378712
PMCPMC13318227

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.