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
Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany.
LipiTUM, Chair of Experimental Bioinformatics, School of Life Sciences, Technical University of Munich, Freising, Germany.
Cell Rep Med. 2025 Jul 15;6(7):102236. doi: 10.1016/j.xcrm.2025.102236.
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.
内镜愈合（EH）是炎症性肠病（IBD）的主要长期治疗目标，主要通过免疫抑制疗法实现。然而，该疾病的慢性和复发性表明存在未知的与组织相关的IBD残留，且会持续终生。基于从患有IBD的儿科患者（N = 32）和儿科非IBD对照（N = 5）纵向收集的胃肠道活检样本（n = 217），我们描述了在EH状态下仍存在于回肠末端和乙状结肠中的IBD的细胞、分子和微生物驱动因素。全活检转录组学结合单细胞T细胞分析（72,026个细胞）表征了一种炎症性肠残留疾病（IBrD）特征，将与应激和炎症相关的组织标志物（如DUOX2、SAA2和NOS2）与产生致病性白细胞介素-17（IL-17）的辅助性T细胞联系起来。16S rRNA基因测序揭示了个体微生物组成，其多样性持续较低，与疾病位置和活动无关。总体而言，我们的研究确定了一种持续存在的IBD特征，该特征反映了尽管实现了EH，但黏膜仍在持续改变。这些标志物可能为未来或序贯治疗提供靶点。
