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

Siebert, Kolja; Faro, Tim; Köhler, Nikolai; Hölz, Hannes; Jarosch, Sebastian; Matchado, Monica; Häcker, Deborah; De Zen, Federica; Hajji, Mohammad Samer; Lurz, Eberhard; Koletzko, Sibylle; Pauling, Josch K.; Steiger, Katja; Neuhaus, Klaus; Ohnmacht, Caspar; List, Markus; Busch, Dirk H.; Haller, Dirk; Schwerd, Tobias (2025): Endoscopic healing in pediatric IBD perpetuates a persistent signature defined by Th17 cells with molecular and microbial drivers of disease. Cell Reports Medicine, 6 (7): 102236. ISSN 26663791

Abstract

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.

• Dokumententyp: Artikel (Klinikum der LMU)
• Organisationseinheit (Fakultäten): 07 Medizin > Klinikum der LMU München > Kinderchirurgische Klinik und Poliklinik im Dr. von Haunerschen Kinderspital
• DFG-Fachsystematik der Wissenschaftsbereiche: Lebenswissenschaften
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 395357507
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 490846870