Abstract Background Mucins are key components of the intestinal mucus barrier and maintain epithelial integrity. While mucin dysregulation is a hallmark of inflammatory bowel diseases (IBD), their cell type-specific expression dynamics and modulation during treatment remain poorly defined. We aimed to construct a mucin mRNA expression atlas at the single-cell level in the intestinal mucosa of ulcerative colitis (UC), Crohn’s disease (CD), and healthy control (HC) patients, and to assess its therapy-associated changes following anti-TNFα treatment. Methods Two publicly available single-cell RNA sequencing datasets were analysed. Dataset 1 (GSE214695) included colonic cells from HC, UC, and CD patients. Dataset 2 (GSE282122) comprised longitudinal gut samples from IBD patients before and after adalimumab therapy. Datasets were annotated using published gut cell-state markers. Expression of 21 mucin genes (MUC1-MUC22) was quantified across annotated cell types to identify mucin-expressing populations and explore expression dynamics across disease states and treatment response. Results Across all patient cohorts, mucin mRNA expression was largely confined to gut epithelial cells, with MUC1, MUC4, MUC12, and MUC13 consistently expressed, alongside MUC2, MUC3A, and MUC5B in select cell populations, forming a conserved epithelial mucin repertoire (Figure 1). Mucin expression patterns were similar between UC and CD, indicating shared epithelial responses to inflammation. In healthy mucosa, goblet cells were enriched for MUC2, followed by MUC4, MUC1, and MUC5B, whereas mature goblet cells showed high MUC2, then MUC1, MUC13, MUC4, MUC12, and MUC3A. In IBD, both goblet populations exhibited markedly increased MUC5B. Colonocytes showed broader perturbations, with upregulation of MUC1, MUC4, and MUC5B and loss of MUC17 and MUC20. Laminin-positive colonocytes demonstrated increased MUC1, MUC2, MUC3A, and MUC5B, alongside reduced MUC12, while PLCG-positive colonocytes also displayed elevated MUC5B. These patterns highlight lineage-specific mucin dysregulation in IBD. Longitudinal analysis revealed region-dependent modulation after adalimumab therapy, with MUC2 and MUC5AC upregulated in ileal but reduced in non-ileal goblet cells, a consistent MUC5B decrease across goblet subsets, and increased MUC12, MUC13, and MUC20 in non-ileal enterocytes post-treatment. Conclusion This single-cell mucin mRNA atlas identifies a conserved core mucin set across epithelial subtypes and shows how their expression is remodelled in IBD and during anti-TNFα therapy. The cell type-specific mucin dynamics highlight mucosal adaptation and epithelial recovery and may support identification of mucin-based biomarkers of treatment response. Conflict of interest: Ms. Gassman, Julie: I am supported by an internal university fund of the Antwerp University (BOF-SEP FFB240386) and a national fund of the Research Foundation - Flanders (Belgium FWO OZ10337). Oosterlinck, Baptiste: Supported by the Antwerp University Valorisation funds (IOF-POC number: FFI230207) De Man, Joris: no conflicts De Winter, Benedicte: grants from the University of Antwerp and the FWO (Fund for scientific research in Flanders) Further no conflicts of interest Smet, Annemieke: Annemieke Smet is supported by an internal university fund of the Antwerp University (BOF-SEP FFB240386) and a national fund of the Research Foundation - Flanders (Belgium FWO OZ10337). Annemieke Smet is also inventor of patent applications related to mucin isoforms in diseases characterized by barrier dysfunction, including IBD, GI cancers and respiratory diseases (WO/2021/013479 WO2022/003061 EP23214719.9).
Gassman et al. (Thu,) studied this question.