The “microbiota-barrier-immunity-signaling” interaction network: novel insights into the pathogenesis of ulcerative colitis and strategies for precision intervention

Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease characterized by continuous mucosal inflammation of the colon, with a protracted course and recurrent episodes. The global disease burden continues to increase, and its incidence in China has also shown an upward trend, making it a significant public health concern in gastroenterology. Recent studies have proposed 4 core mechanisms underlying the pathogenesis of UC: ① Gut microbiota dysbiosis participates in disease progression through multiple steps of “structural alteration of microbiota-metabolic dysfunction-barrier impairment-aberrant immune activation”. Reduced short-chain fatty acids (SCFAs)-producing bacteria weaken the production of anti-inflammatory metabolites, and expansion of opportunistic pathogens promotes inflammatory stimulation; ② Intestinal barrier dysfunction serves as critical hub connecting the microbiota and the immune system. Downregulation of tight junction proteins and thinning of the mucus layer allow luminal antigens to more easily penetrate into the lamina propria, triggering an immune cascade; ③ Dual imbalance of innate and adaptive immunity constitutes the foundation for sustained amplification of inflammation. Macrophage M1 polarization, neutrophil extracellular trap (NET) formation, and Th17/Treg imbalance collectively drive chronic inflammation; ④ Aberrant activation and cross-talk among multiple signaling pathways, including TLR/NF-κB, JAK/STAT, and autophagy, create a pathological cycle of “initial inflammation-tissue injury-secondary inflammation”. Currently, the therapeutic strategy for UC is shifting from traditional 5-aminosalicylates and corticosteroids toward precision-targeted interventions: biologics and small-molecule drugs [e. g., anti-TNF-α preparation, anti-integrin preparation, JAK inhibitors, sphingosine-1-phosphate receptor (S1PR) modulators] achieve precise immune regulation by blocking key inflammatory cytokines or modulating immune cell migration. Microecological interventions (fecal microbiota transplantation, phage therapy) provide new approaches for microbiota remodeling. Traditional Chinese medicine (e. g., Baitouweng Decoction, Gegen Qinlian Decoction) serves as a complementary strategy through multi-target regulation. Surgical treatment remains an important backup for medically refractory UC. In the future, research on UC prevention and treatment should shift from single-target intervention toward systematic dissection of the core regulatory nodes within the “microbiota-barrier-immunity-signaling” interaction network. Moreover, relying on a multidisciplinary team (MDT) model encompassing internal medicine, surgery, nutrition, and psychology, diagnostic and therapeutic strategies should be advanced from symptom control to precision immunomodulation, microbiota remodeling, barrier repair, and whole-disease-course management, thereby laying a solid theoretical and practical foundation for improving individualized treatment and long-term benefits for UC patients.