Yu KX, Lu ZJ. Circadian clock at the interface of mucosal immunity, gut microbiota and epithelial barrier in inflammatory bowel disease. World J Gastroenterol 2026; 32(22): 118745 [DOI: 10.3748/wjg.v32.i22.118745]
Corresponding Author of This Article
Zhan-Jun Lu, MD, PhD, Chief Physician, Department of Gastroenterology, Jintan Affiliated Hospital of Jiangsu University, No. 500 Jintan Avenue, Jintan 213200, Jiangsu Province, China. zhanjun.lu@shgh.cn
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Microbiology
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review-article
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Yu KX, Lu ZJ. Circadian clock at the interface of mucosal immunity, gut microbiota and epithelial barrier in inflammatory bowel disease. World J Gastroenterol 2026; 32(22): 118745 [DOI: 10.3748/wjg.v32.i22.118745]
World J Gastroenterol. Jun 14, 2026; 32(22): 118745 Published online Jun 14, 2026. doi: 10.3748/wjg.v32.i22.118745
Circadian clock at the interface of mucosal immunity, gut microbiota and epithelial barrier in inflammatory bowel disease
Ke-Xin Yu, Zhan-Jun Lu
Ke-Xin Yu, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu Province, China
Zhan-Jun Lu, Department of Gastroenterology, Jintan Affiliated Hospital of Jiangsu University, Jintan 213200, Jiangsu Province, China
Author contributions: Yu KX conceptualized the study and wrote the original draft; Lu ZJ supervised the study and reviewed and edited the manuscript. Both authors approved the final version to publish.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Zhan-Jun Lu, MD, PhD, Chief Physician, Department of Gastroenterology, Jintan Affiliated Hospital of Jiangsu University, No. 500 Jintan Avenue, Jintan 213200, Jiangsu Province, China. zhanjun.lu@shgh.cn
Received: January 12, 2026 Revised: January 31, 2026 Accepted: March 17, 2026 Published online: June 14, 2026 Processing time: 139 Days and 22.4 Hours
Abstract
Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a group of chronic relapsing disorders caused by dysregulated mucosal immunity, altered gut microbiota, and impaired epithelial barrier function. There is increasing evidence linking circadian disruptions, such as shift work, jet lag, sleep loss, light misalignment, and irregular eating patterns, to the risk of IBD and associated symptoms and inflammatory activity. The intestinal circadian system is coordinated by the central clock and peripheral clocks in epithelial and immune cells. These oscillators stimulate innate and adaptive immune responses; shape diurnal microbial rhythms and metabolite production; and regulate epithelial tight junctions, mucus production, antimicrobial peptides, and regenerative programs. Microbial metabolites (short-chain fatty acids, bile acids, and tryptophan derivatives) can entrain host clocks, creating a bidirectional immunity-microbiota-barrier network. This minireview synthesizes mechanistic and clinical data on circadian clock gene networks in IBD. It highlights translational opportunities for chronotherapy (e.g., regular meal timing and sleep-light alignment) and discusses why time-of-day optimization of pharmacotherapy for IBD remains exploratory, with limited and heterogeneous evidence across major drug classes (5-aminosalicylic acid, systemic corticosteroids, biologics, and small molecules).
Core Tip: Disrupted circadian clock gene networks link mucosal immune imbalance, gut microbiota dysbiosis, and epithelial barrier failure in inflammatory bowel disease. Chronotherapy, particularly behavioral interventions, such as stabilizing sleep-wake schedules and meal timing, is a plausible avenue. However, evidence supporting medication timing in the treatment of IBD remains limited and heterogeneous. Thus, rigorous prospective trials are needed before clinical recommendations can be made.
