Tripartite Interplay of Epithelial, Immune, and Microbiota Dysregulation in Crohn's Disease: Mechanisms and Translational Strategies

Abstract

ABSTRACT Background Crohn's disease (CD) is a multifactorial inflammatory bowel disease (IBD) characterized by impaired epithelial barrier integrity, excessive immune hyperactivation, and gut microbiota perturbations. Cumulative evidence supports the role of the intestinal epithelial barrier, immune system and gut microbiota in the progression of CD. Objective This review constructs a mechanistic framework of the epithelial‐immune‐microbiota tripartite network in CD with a focus on positive‑feedback circuits sustaining persistent intestinal inflammation. Key Findings Interrelated pathological loops involving barrier injury, immune activation and microbial dysbiosis perpetuate chronic intestinal inflammation and provide a rationale for mechanism‑guided combinatorial therapeutic interventions. Conclusions This framework illuminates key pathogenic crosstalk that may be targeted to optimize future treatment regimens for CD.