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THE CCR9/CCL25 AXIS IS SPECIFIC TO THE ILEUM AND IS CORRELATED WITH STRICTURING DISEASE

Gerben Bouma 1, Ulf Gehrmann 2, Eszter Csomor 1, Sue Monkley 2, Benjamin Georgi 2, Sun Tian 1, Ana Laura Moldoveanu 1, Junmei Cairns 2, Bastian Angermann 2, Emon Khan 1, Josquin Nys 1, Daniel Marks 1

Affiliations

1 AstraZeneca, Cambridge, United Kingdom

2 AstraZeneca, Gothenburg, Sweden

Summary

AI Generated

Transcriptomic analysis of 611 Crohn's disease patients identifies the CCR9/CCL25 chemokine axis as specifically expressed in the terminal ileum and upregulated in penetrating and stricturing disease, suggesting a potential therapeutic target for small bowel Crohn's disease.

CCR9 and its ligand CCL25 showed expression specific to the terminal ileum with minimal activity in the colon, in contrast to the ubiquitous gut expression of vedolizumab targets ITGA4, ITGB7, and MADCAM1
CCL25 expression was significantly increased in patients with penetrating and stricturing Crohn's disease, a high-impact disease feature associated with ileal disease that represents an unmet need
An expression quantitative trait locus upstream of the CCL25 promoter was linked to small bowel CCL25 expression
The findings suggest that small bowel Crohn's disease may have been incompletely targeted by small molecule inhibitors to date and support exploring CCR9/CCL25 axis therapies
All authors were AstraZeneca employees holding company stocks during the study

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Abstract

Introduction

Crohn’s Disease (CD) is a chronic disease in which inflammation is sustained by continuous influx of inflammatory leukocytes into gut mucosa and may affect all segments of the gastrointestinal tract. Immune cell trafficking is regulated via chemokine gradients and adhesion molecules such as integrins. Here we explored the expression profile of gut-specific integrin and chemokine axes in different regions of the gut to identify possible targets for treating CD patients with different disease location or phenotype.

Aims & Methods

This study used transcriptomic data from gut tissue biopsies of the large and small intestine of 611 CD and 315 UC patients enrolled in a multicentred longitudinal Study of a Prospective Adult Research Cohort with IBD (SPARC IBD) obtained from the IBD Plexus program of the Crohn’s and Colitis Foundation. We mapped the expression of selected chemokine receptors and their ligands as well as gut-specific integrins onto the different segments of the intestine. Expression data were then linked to available clinical disease phenotypes, as well as genotype information.

Results

In both CD and UC patients, ITGA4 and ITGB7, the targets for Vedolizumab, and their endothelial ligand MADCAM1 were ubiquitously present in all regions of the gut. GPR15 and its ligand C10orf99 were predominantly expressed in colonic biopsies. On the contrary, expression of CCR9 and its ligand CCL25 were specific to the terminal ileum with only minimal transcriptional activity in the colon. Expression of CCL25 was significantly increased in patients with penetrating and/or stricturing CD, a disease feature associated with ileal CD that has high impact for patients and is currently an unmet for IBD patients. Further, we identified an expression quantitative trait loci (eQTL) upstream of the CCL25 promoter linked to small bowel expression of CCL25.

Conclusion

Our data highlight the potential for targeting the CCR9/CCL25 axis as a treatment for small bowel Crohn’s Disease which may have been incompletely targeted to date by small molecule inhibitors.

Disclosure

All authors were employees of AstraZeneca during the conduct of the study and hold AstraZeneca stocks or stock options.

Conference

UEG Week Copenhagen 2023

Topics

Small Intestine & Nutrition

Submission format

Abstract

Session

PP 03 Small intestinal (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

More Like This:

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY UPTAKE CHARACTERISTICS AS PREDICTORS OF COLORECTAL NEOPLASTIC LESIONS ON COLONOSCOPY: A SINGLE-CENTER STUDY

Seung Wook Hong

AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

Valery Naranjo

UEG Presentation

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TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

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TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rahul Ravindran 1, Drishya Iyer 2, Daniel Lee 2, Meghan Blitchington 3, Christopher Huckstep 2, Riley Telkamp 3, Kevin Telfer 2, Lillian O'Neal 3, Rachel Mintz 2, Deanna Davis 2, Kibeom Park 2, Nadav Yayon 1, Shashi Kumar 2, Alexandre Gallerand 2, Ahmed Hedayat 2, Changqing Ma 2, Mark Hoofnagle 2, Raphael Blain 4, Adrien Hallou 4, Young-Kwon Hong 5, Simon Travis 4, Matthias Friedrich 4, Huaibin Ko 6, Ryan C. Ungaro 6, Chao Zhou 2, Jean-Frédéric Colombel 6, Fiona Powrie 4, Mark Coles 4, Christopher Buckley 4, Bernd Zinselmeyer 2, Gwendalyn Randolph 2, Rafael Czepielewski 3

Affiliations

1 University of Cambridge, Cambridge, United Kingdom

2 Washington University in St. Louis, Saint Louis, United States

3 Augusta University, Augusta, United States

4 University of Oxford, Oxford, United Kingdom

5 Harvard Medical School, Boston, United States

6 Icahn School of Medicine at Mount Sinai, New York City, United States

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Abstract

Introduction

The lymphatic vasculature is essential for tissue homeostasis, yet the organisation and function of colonic lymphatics remain poorly defined compared with those of the small intestine. In particular, how lymphatic vessels integrate with the structural landscape of the colon to regulate interstitial fluid drainage and immune organisation is not well understood.

Aims & Methods

This study aimed to define the anatomical organisation of colonic lymphatic vessels and determine how tissue architecture influences interstitial fluid drainage and immune positioning. Using whole-organ imaging, we examined the spatial development and distribution of colonic initial lymphatic vessels. To assess drainage pathways, exogenous and endogenous tracers were tracked through the colonic interstitium. The spatial relationships among lymphatic vessels, blood vessels, macrophages, and lymphoid tissue were also analysed. Finally, tissue architecture was examined under inflammatory conditions using human ulcerative colitis samples and a DSS-induced colitis mouse model.

Results

Colonic initial lymphatic vessels developed postnatally and were positioned beneath epithelial crypts. These crypts were embedded within a pre-existing macroscopic tissue landscape characterised by tent-like folds, which created prominent interstitial pockets beneath them. Tracer tracking revealed that interstitial fluid outflow was not uniform but instead followed geometry-dependent drainage pathways defined by these folds. Colon folds spatially coordinated lymphatic vessels, blood vessels, macrophages, and lymphoid tissue, forming integrated stromal-vascular-immune reservoirs positioned to receive and concentrate interstitial cargo. In inflammatory conditions, human ulcerative colitis tissue showed focal loss of folds at sharp boundaries between inflamed and adjacent healthy regions. Consistently, during DSS-induced colitis, folds widened in an accordion-like manner over an expanding submucosa, indicating that fold geometry dynamically adapts under inflammatory stress.

Conclusion

These findings identify colon folds as anatomical scaffolds that organise lymphatic, vascular, and immune components to create specialised drainage routes within the tissue. Tissue geometry therefore emerges as a major organiser of colonic drainage architecture. Disruption of this structural framework during inflammation may compromise interstitial drainage and immune positioning.

References

Czepielewski, R. S. et al. Ileitis-associated tertiary lymphoid organs arise at lymphatic valves and impede mesenteric lymph flow in response to tumor necrosis factor. Immunity 54, 2795-2811 e2799 (2021).
Nava, G. M., Friedrichsen, H. J. & Stappenbeck, T. S. Spatial organization of intestinal microbiota in the mouse ascending colon. ISME J 5, 627-638 (2011).
Randolph, G. J., Ivanov, S., Zinselmeyer, B. H. & Scallan, J. P. The Lymphatic System: Integral Roles in Immunity. Annual Review of Immunology 35, 31-52 (2017).
Uzzan, M. et al. Ulcerative colitis is characterized by a plasmablast-skewed humoral response associated with disease activity. Nat Med 28, 766-779 (2022).

Event

UEG Week Barcelona 2026

Topics

Gut Microbiota Mechanisms & Personalised Medicine Immunology IBD

Submission format

Abstract

Session

New insights into IBD mechanisms

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY UPTAKE CHARACTERISTICS AS PREDICTORS OF COLORECTAL NEOPLASTIC LESIONS ON COLONOSCOPY: A SINGLE-CENTER STUDY

Seung Wook Hong

AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

Valery Naranjo

UEG Presentation

New

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Predicting outcomes based on B-cell profiles

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Predicting outcomes based on B-cell profiles

Arno R. Bourgonje 1

Affiliations

1 University Medical Center of Groningen, Groningen, Netherlands

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Abstract

Event

UEG Week Barcelona 2026

Topics

Immunology Mechanisms & Personalised Medicine IBD

Session

Disease primer: Unexpected cellular players in IBD

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY UPTAKE CHARACTERISTICS AS PREDICTORS OF COLORECTAL NEOPLASTIC LESIONS ON COLONOSCOPY: A SINGLE-CENTER STUDY

Seung Wook Hong

AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

Valery Naranjo

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

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A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Luca Massimino 1, Sabrina Nicolo' 1, Tommaso Lorenzo Parigi 1, Sara Mino 2, Mattia Bugatti 2, Francesca Nicola 1, Nicola Ivan Lorè 1, Vincenzo Villanacci 2, Paola Parente 3, Fabrizio Bossa 4, Orazio Palmieri 5, Pierpaolo Sileri 1, Silvio Danese 6, Federica Ungaro 1

Affiliations

1 Ospedale San Raffaele, Milano, Italy

2 Institute of Pathology, ASST Spedali Civili and University of Brescia, Brescia, Italy

3 Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

4 Fondazione Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

5 Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy

6 Vita-Salute San Raffaele University - IRCCS San Raffaele Scientific Institute, Milan, Italy

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Abstract

Introduction

Fistulizing Crohn’s disease represents a severe and disabling complication characterized by transmural inflammation and aberrant tissue remodeling. Although fissures are considered precursors of fistulas, the cellular and molecular mechanisms driving this transition remain poorly defined. We aimed to characterize the spatial immune-stromal interactions underlying fissure formation and progression toward fistula.

Aims & Methods

Spatial transcriptomics was performed on intestinal surgical specimens from Crohn’s disease patients with inflamed tissue, increasing-depth fissures, and entero-enteric fistulas. Spatial data were integrated with single-cell reference datasets and pseudotime analysis to reconstruct stromal and myeloid differentiation trajectories and were utilized to identify ligand-receptor signaling networks across defined tissue compartments.

Results

Fissure-associated regions were enriched in inflammatory fibroblasts and inflammatory monocytes, identifying fissures as active immune-stromal niches rather than passive structural defects. Pseudotime reconstruction revealed coordinated differentiation programs in which stromal cells and myofibroblasts transitioned into inflammatory fibroblasts, while inflammatory monocytes differentiated into macrophages and LAMP3⁺ dendritic cells. Ligand-receptor analysis demonstrated a progressive shift from early chemokine-mediated recruitment dominated by CXCL12-CXCR4 signaling to adhesion- and retention-mediated circuits involving Complement, ADGRE5-CD55, and THY1-integrin pathways. These changes established a spatially confined and self-sustaining immune-stromal microenvironment in advanced fissures and fistulas.

Conclusion

Fissures represent active immune-stromal niches that initiate and sustain cellular and molecular programs driving fistula formation. The transition from chemokine-driven recruitment to adhesion-mediated immune retention defines a key mechanistic step in fistulization. These findings identify early fissures as a potential therapeutic window and highlight CXCR4, Complement, and immune-stromal adhesion pathways as candidate targets to prevent fistula development in Crohn’s disease.

Event

UEG Week Barcelona 2026

Topics

Mechanisms & Personalised Medicine Immunology IBD

Submission format

Abstract

Session

Immunologic pathways of disease and drug response in IBD

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY UPTAKE CHARACTERISTICS AS PREDICTORS OF COLORECTAL NEOPLASTIC LESIONS ON COLONOSCOPY: A SINGLE-CENTER STUDY

Seung Wook Hong

AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

Valery Naranjo

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

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BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

E.A.M. (Noortje) Festen 1, Paola Pibiri 2, Roy Oelen 2, Werna T. C. Uniken Venema 3, Emilia Bigaeva 1, Monique G.P. Van der Wijst 2, Maria Paraskevopoulou 4, Klaas Nico Faber 2

Affiliations

1 UMCG, Groningen, Netherlands

2 University Medical Center Groningen, Groningen, Netherlands

3 Zuyderland Medisch Centrum, Leuven, Belgium

4 Takeda Pharmaceuticals, Acton, United States

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Abstract

Introduction

Ulcerative colitis (UC) and Crohn’s disease (CD) share chronic intestinal inflammation but differ in clinical behavior and treatment response. Although single-cell RNA sequencing (scRNA-seq) studies have advanced understanding of IBD biology, limited sample sizes have hindered robust comparison of shared versus disease-specific mechanisms. We therefore performed a large-scale meta-analysis of gut mucosal scRNA-seq datasets to define common inflammatory architecture and divergent immune programs in UC and CD.

Aims & Methods

Gut mucosal scRNA-seq datasets from two CD and two UC cohorts were integrated using a standardized computational workflow for preprocessing, harmonization, and downstream analysis. Cell-type annotation, differential abundance and gene expression analyses, pathway enrichment, and cell–cell communication inference were performed to compare inflamed and non-inflamed tissue within each disease and identify shared versus disease-specific programs.

Results

We generated disease-specific atlases comprising more than 405,000 cells from approximately 190 patients with CD and 313,000 cells from approximately 72 patients with UC. Across both diseases, inflammation followed a shared remodeling program marked by epithelial cell loss, expansion of immune populations, and activation of immune-related pathways. Despite this common inflammatory framework, immune execution diverged by disease. In CD, CD8+ T cells declined in inflamed tissue, whereas in UC they expanded together with other immune subsets. B cells showed a similar contrast, with enrichment of innate and stress-response pathways in CD versus adaptive and humoral immune programs in UC. Monocytes added further specificity, with strong enrichment of JAK-STAT signaling observed only in UC. Consistently, cell-cell communication analysis indicated stronger adaptive immune interactions in UC than in CD.

Conclusion

UC and CD share a common inflammation-associated tissue remodeling program, but diverge in the immune pathways and cellular interactions that dominate the inflamed mucosa. These findings provide a systems-level framework for understanding IBD heterogeneity and may help prioritize phenotype-specific therapeutic targets.

References

1. Martin, J. C. et al. Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy. Cell 178, 1493-1508.e20 (2019).
2. Smillie, C. S. et al. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis. Cell 178, 714-730.e22 (2019).
3. Jaeger, N. et al. Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions. Nat. Commun. 12, 1921 (2021).
4. Calviño-Suárez, C. et al. Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response. Front. Immunol. 16, 1609740 (2025).

Event

UEG Week Barcelona 2026

Topics

Gut Microbiota Mechanisms & Personalised Medicine Immunology IBD

Submission format

Abstract

Session

New insights into IBD mechanisms

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY UPTAKE CHARACTERISTICS AS PREDICTORS OF COLORECTAL NEOPLASTIC LESIONS ON COLONOSCOPY: A SINGLE-CENTER STUDY

Seung Wook Hong

AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

Valery Naranjo

UEG Poster

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FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY UPTAKE CHARACTERISTICS AS PREDICTORS OF COLORECTAL NEOPLASTIC LESIONS ON COLONOSCOPY: A SINGLE-CENTER STUDY

Ji Yun Oh 1, Hyeong Jin Kim 1, Ju Eon Hong 1, Yeo Jin Lee 1, Hong Shin Cho 1, Min Kyu Kim 1, Sung Wook Hwang 1, Sang Hyoung Park 1, Dong-Hoon Yang 1, Byong Duk Ye 1, Jeong-Sik Byeon 1, Seung Wook Hong 1

Affiliations

1 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of

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Abstract

Introduction

Fluorodeoxy-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used in cancer diagnosis and staging in clinical practice. However, the correlation between colorectal PET/CT uptake characteristics and clinically significant colonoscopic findings remains limited.

Aims & Methods

This study aimed to evaluate the association between PET/CT uptake characteristics and colorectal neoplastic lesions, and to assess their predictive factors. We retrospectively reviewed the medical records of patients with colorectal uptake on PET/CT at Asan Medical Center between January 2000 and August 2025 who underwent colonoscopy within 90 days. Patients were categorized based on the presence or absence of colonoscopic lesions. Multivariable analysis was performed to identify factors associated with colorectal neoplastic lesions.

Results

Out of total 656 patients with colonic uptake on PET/CT, colonoscopy confirmed corresponding lesions in 514 (78.4%) patients. Multivariable logistic regression revealed that a focal uptake pattern (Odds Ratio [OR] 2.36, 95% CI 1.20–4.64, p = 0.013) and a maximum standardized uptake value (SUVmax) ≥8.7 (OR 2.94, 95% CI 1.94–4.45, p < 0.001) were independent predictors of colorectal lesions detection. Conversely, female (OR 0.48, p < 0.001) and PET/CT performed for cancer recurrence work-up (OR 0.31, p < 0.001) were associated with a lower likelihood of detecting a lesion. Among the 514 patients with detected lesions, 421 (81.9%) were colorectal neoplastic lesions (I.e., pre-cancerous polyps and primary adenocarcinomas) and 93 (18.1%) were non-adenomatous lesions (i.e., non-neoplastic conditions and non-epithelial or metastatic malignancies). In a subsequent analysis, older age (OR 1.05, 95% CI 1.03–1.07, p < 0.001), distal colonic location (OR 2.76, 95% CI 1.61–4.74, p < 0.001), and SUVmax ≥ 8.7 (OR 1.81, 95% CI 1.11–2.94, p = 0.018) were independent predictors of neoplastic lesions.

Conclusion

FDG PET/CT uptake characteristics, particularly focal uptake pattern and SUVmax ≥ 8.7, are significant predictors of colorectal lesion detection. Among detected lesions, older age, distal colonic location, and SUVmax ≥ 8.7 independently predict neoplastic pathology. These findings may help guide clinical decision-making regarding colonoscopy referral in patients with incidental colorectal FDG uptake.

References

1.Haejun Lee, et al. Focal incidental colorectal fluorodeoxyglucose uptake: should it be spotlighted?. World Journal of Clinical Cases. 2024.
2.Demirci, S., et al. Incidental focal 18F-FDG uptake in colorectal locations on PET/CT for oncologic reasons: pathologic correlation with endoscopic findings. Journal of Health Sciences and Medicine. 2025.
3.Luis Correia Gomes, et al. Incidental Uptake in Gastrointestinal Tract on 18F-FDG-PET/CT: Is It Worth to Investigate? A Study with 371 Patients. GE Portuguese Journal of Gastroenterology. 2024.

Conference

UEG Week Barcelona 2026

Topics

Colorectal

Submission format

Abstract

Session

Colorectal cancer: How can we improve treatment? (Posters)

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

More Like This:

TISSUE FOLDS ORGANISE COLON LYMPHATICS TO CHANNEL INTERSTITIAL OUTFLOW AND PROMOTE RESILIENCE AGAINST INFLAMMATORY SWELLING

Rafael Czepielewski

Predicting outcomes based on B-cell profiles

Arno R. Bourgonje

A SPATIALLY ORGANIZED IMMUNE-STROMAL PROGRAM DRIVES THE FISSURE-TO-FISTULA CONTINUUM IN CROHN’S DISEASE

Federica Ungaro

BIOPSY-BASED SINGLE-CELL PROFILING OF ULCERATIVE COLITIS AND CROHN’S DISEASE REVEALS SHARED INFLAMMATORY ARCHITECTURE AND DISEASE-SPECIFIC IMMUNE PATHWAYS

Klaas Nico Faber

FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY UPTAKE CHARACTERISTICS AS PREDICTORS OF COLORECTAL NEOPLASTIC LESIONS ON COLONOSCOPY: A SINGLE-CENTER STUDY

Seung Wook Hong

AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

Valery Naranjo

UEG Presentation

New

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

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AI-DRIVEN PROBE CONFOCAL LASER ENDOMICROSCOPY ENABLES AUTOMATED ASSESSMENT OF INTESTINAL BARRIER IMPAIRMENT IN IBD

Marietta Iacucci 1,2, Irene Zammarchi 1, Ilan Carretero 3, Pablo Meseguer 3, Cecilia Lina Pugliano 1, Giovanni Santacroce 1, Rocio Del Amor 3,4, Ujwala Chaudhari 5, Bisi Bode Kolawole 5, Rory Crotty 6, Brian Hayes 6, Subrata Ghosh 1, Enrico Grisan 5, Valery Naranjo 3,4

Affiliations

1 University College Cork, Cork, Ireland

2 University of Calgary, Calgary, Canada

3 Universitat Politècnica de València, Valencia, Spain

4 Artikode Intelligence S.L., Valencia, Spain

5 London South Bank University, London, United Kingdom

6 Cork University Hospital, Cork, Ireland

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Abstract

Introduction

Barrier healing is emerging as a key therapeutic target in Inflammatory bowel disease (IBD), and is increasingly associated with improved long-term outcomes than endoscopic and histological remission alone. However, objective and reproducible assessment of barrier integrity remains challenging. Probe-based confocal laser endomicroscopy (pCLE) enables real-time structural and functional assessment of epithelial and vascular barrier features, including villi and crypt architecture, goblet cells, fluorescein leakage and vessel architecture. However, its interpretation remains complex and highly operator-dependent, limiting reproducibility and widespread application. ¹. We aimed to develop and validate an artificial intelligence (AI)-driven pCLE system for automated standardised assessment of epithelial and vascular barrier impairment (BI) in IBD.

Aims & Methods

A total of 297 high-quality pCLE videos from IBD patients undergoing colonoscopy in two tertiary centers (University College Cork, Ireland and University of Calgary, Canada) were considered. Experienced endoscopists assessed the presence of overall barrier and feature-specific impairment according to a previously developed pCLE-scoring system ², providing a reference standard for AI. 196 videos from the Calgary cohort were used to train and validate the framework (using cross-validation) and 101 videos from the Cork cohort were considered for external validation.
An AI algorithm was developed to predict pCLE-based overall- and feature-level BI using a weakly supervised learning paradigm that exclusively employs video-level scoring. First, frame-level representations were extracted with a DINOv2 foundation model³. Later, a multiple instance learning (MIL) model aggregates frame-features into a global representation to produce the predicted score of the video⁴. The model’s diagnostic performance to predict overall, epithelial, vascular and feature-level impairment was evaluated.

Results

Overall, 297 videos from 141 IBD patients were considered. BI was detected in 187/297 (63.0%) videos, including 68/101 (67.3%) in Cork and 119/196 (60.7%) in the Calgary cohort.
Table 1 details the diagnostic performance of the model. The AI algorithm achieved remarkable performance in both the development and validation cohorts, with 71.4% (95% 63.3-79.5) and 89.7% (95% CI 82.3-97.1) sensitivity, 71.4% (95% CI 61.3-81.5) and 39.4% (95% CI 22.7-56.1) specificity, 71.4% (95% CI 65.1-77.8) and 73.3% (95% CI 64.6-81.9) accuracy, and 0.77 and 0.72 AUC for detecting overall BI at the video level. Performance remained consistent for most epithelial and vascular components, although slightly lower for villi/crypts architecture and goblet cells, likely reflecting the more challenging assessment of these features with pCLE.

	Overall BI	Epithelial BI	Vascular BI	Villi/ crypts architecture	Goblet cells	Vessel architecture	Fluorescein leakage
Development cohort (N=196)
AUC % (95% CI)	0.77	0.74	0.77	0.80	0.78	0.78	0.77
F1 score % (95% CI)	75.2 (68.8-81.6)	74.2 (67.5-80.9)	75.3 (68.7-81.9)	68.6 (59.0-78.0)	76.5 (70.0-83.0)	63.5 (54.1-72.7)	76.5 (70.2-82.8)
Accuracy % (95% CI)	71.4 (65.1-77.8)	70.9 (64.4-77.3)	70.9 (64.4-77.3)	78.1 (72.3-83.9)	74.0 (67.9-80.1)	68.9 (62.4-75.4)	72.5 (66.2-78.6)
Validation cohort (N=101)
AUC % (95% CI)	0.72	0.71	0.75	0.58	0.73	0.79	0.74
F1 score % (95% CI)	81.9 (72.4-89.6)	69.6 (60.0-79.2)	79.2 (70.9-87.3)	47.9 (35.2-60.6)	53.1 (42.1-64.1)	75.9 (66.2-85.6)	77.7 (69.8-85.6)
Accuracy % (95% CI)	73.3 (64.6-81.9)	59.4 (49.8-68.9)	70.3 (61.4-79.2)	50.5 (40.8-60.2)	47.5 (42.1-64.1)	72.3 (63.6-81.0)	69.3 (60.4-78.2)

Table. Diagnostic performance of the AI algorithm to predict barrier impairment on pCLE videos.

Conclusion

Our AI-driven pCLE enables automated, standardised in vivo assessment of epithelial and vascular barrier features, offering an objective, reproducible tool to monitor barrier healing as a novel therapeutic endpoint in IBD.

References

1. Iacucci M, Jeffery L, Acharjee A, et al. Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study. Inflamm Bowel Dis. 2023;29(9):1409-1420. doi:10.1093/ibd/izac233
2. Iacucci M, Majumder S, Zammarchi I, et al. Automated real-time imaging of intestinal barrier integrity and molecular profiling for early outcome prediction in inflammatory bowel disease - Endo-Histo-Barrier-Omics study. J Crohns Colitis.
3. Oquab M, Darcet T, Moutakanni T, et al. DINOv2: Learning Robust Visual Features without Supervision. Published online February 2, 2024.
4. Carretero I, Meseguer P, et al. Time-aware semantic prototypes for weakly-supervised endomicroscopy video classification. Published online April, 2026.

Event

UEG Week Barcelona 2026

Topics

Colorectal IBD

Submission format

Abstract

Session

IBD diagnostics: In search of optimal implementation

Citation

2026: United European Gastroenterology Journal 2026; 14 (S1)

Published

2026

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