Current Perspectives on the Inflammatory Bowel Disease Pathogenesis of Microbiota and the Gut-Brain Axis, and Emerging Therapeutics

The pathogenesis of inflammatory bowel disease (IBD) is driven by an interplay among intestinal dysbiosis and aberrant mucosal immune responses. This review centers on the microbiota as a pivotal pathogenic hub, systematically dissecting how three hallmark features of dysbiosis-reduced microbial alpha diversity, depletion of immunomodulatory commensals, and expansion of pro-inflammatory pathobionts-collectively compromise epithelial barrier function, promote bacterial translocation, and sustain chronic mucosal inflammation. We further integrate emerging evidence implicating bidirectional gut-brain axis communication in amplifying both peripheral inflammation and central nervous system (CNS)-mediated behavioral comorbidities. Building on this mechanistic framework, we critically evaluate next-generation microbiota-targeted interventions: standardized fecal microbiota transplantation (FMT), rationally designed live biotherapeutic products (LBPs), precision phage cocktails targeting defined pathobionts, and microbiome-informed dietary strategies. Collectively, these approaches represent a paradigm shift-from broad-spectrum immunosuppression toward mechanism-guided, ecosystem-level modulation-thereby advancing the goal of precision medicine in IBD.