Huang, Zhaoyu; Brown, Monica E.; Lau, Ken S. (2026).Ìý.ÌýCurrent Opinion in Gastroenterology, 42(4), 247–254.Ìý
Current treatments for inflammatory bowel disease, or IBD, mostly focus on the immune system, but many patients still do not get long-lasting relief. This review argues that part of the problem may lie in the intestinal lining itself, where specialized epithelial cells help control inflammation, keep microbes in check, and support healing. Recent single-cell, spatial, and functional studies, which examine cells in much finer detail and in their tissue context, have shown that these secretory epithelial cells are not just passive barriers but active players in gut health. The review highlights three important cell types. Goblet cells, which produce mucus, appear to vary by location in the gut and may influence where disease develops and how severe it becomes. Tuft cells, which detect chemical signals in the gut, seem to link what is happening in the intestinal lumen to immune and nerve-related responses, and may also help drive repair after injury. Paneth cells, which help protect the intestine with antimicrobial substances, often function abnormally in Crohn’s disease affecting the small intestine, while ulcerative colitis in the colon can trigger Paneth-like changes in cells involved in healing. Overall, the review shows that these epithelial cells play an active role in controlling barrier strength and immune responses during chronic inflammation. Understanding these cell states more clearly could help doctors identify different patient subtypes and develop treatments that target the intestinal lining as well as the immune system.
FIGURE 1
Goblet cells in IBD pathophysiology. Cell subset heterogeneity and regional heterogeneity dictates goblet cell function along the GI tract. Goblet cell dysfunction in Crohn’s disease (CD) and ulcerative colitis (UC), highlighting altered sensing and secretory programs and disrupted mucus architecture associated with increased microbial proximity. The summary table compares key goblet cell–related defects in CD versus UC.