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Siebert, K.* ; Faro, T.* ; Köhler, N.* ; Hölz, H.* ; Jarosch, S.* ; Matchado, M.* ; Häcker, D.* ; De Zen, F.* ; Hajji, M.S.* ; Lurz, E.* ; Koletzko, S.* ; Pauling, J.K.* ; Steiger, K.* ; Neuhaus, K.* ; Ohnmacht, C. ; List, M.* ; Busch, D.H.* ; Haller, D.* ; Schwerd, T.*

Endoscopic healing in pediatric IBD perpetuates a persistent signature defined by Th17 cells with molecular and microbial drivers of disease.

Cell Rep. Med. 6:102236 (2025)

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Endoscopic healing (EH) is the major long-term treatment target for inflammatory bowel diseases (IBDs), mainly achieved by immune-suppressive therapies. However, the chronic and relapsing nature of the disease indicates a lifelong persistence of unknown tissue-associated IBD residues. Based on longitudinally collected gastrointestinal biopsies (n = 217) from pediatric patients with IBD (N = 32) and pediatric non-IBD controls (N = 5), we describe cellular, molecular, and microbial drivers of IBD that persist under EH in the terminal ileum and sigmoid colon. Whole biopsy transcriptomics in combination with single T cell analysis (72,026 cells) characterizes an inflammatory bowel residual disease (IBrD) signature, connecting stress- and inflammation-related tissue markers (e.g., DUOX2, SAA2, and NOS2) with pathogenic interleukin-17 (IL-17)-producing T helper cells. 16S rRNA gene sequencing reveals individual microbial composition with persistently low diversity, irrespective of disease location and activity. Overall, our study identifies a persisting IBD signature that reflects ongoing mucosal alterations despite EH. These markers may provide targets for future or sequential therapies.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Duox2 ; Ibd Signature ; Nos2 ; Saa2 ; Th17 ; Bulk Rna ; Endoscopic Healing ; Mucosal 16s Rrna ; Pediatric Ibd ; Single Cell

ISSN (print) / ISBN 2666-3791

e-ISSN 2666-3791

Journal Cell Reports Medicine

Quellenangaben Volume: 6, Issue: 7, Article Number: 102236

Publisher Cell Press

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Allergy Research (IAF)