Gut Microbiota-Driven Neuroimmune Crosstalk in Ulcerative Colitis: From Mechanisms to Therapeutic Implications

Ulcerative colitis (UC) is a chronic inflammatory disease in which epithelial barrier injury, microbial perturbation, dysregulated mucosal immunity, and altered neural signaling converge. Although dysbiosis is frequently reported in UC, taxonomic shifts alone do not explain how microbial signals are translated into mucosal inflammation, urgency, pain, relapse, or heterogeneous therapeutic responses. This review develops a focused framework of gut microbiota -driven neuroimmune crosstalk, defined as bidirectional communication through which microbial communities and their metabolites regulate epithelial, neuronal, glial, enteroendocrine, and immune compartments, while neural and immune signals reshape barrier function and microbial ecology. We synthesize evidence on short-chain fatty acids, tryptophan-derived indoles, serotonin signaling, bile acids, microbe-associated molecular patterns, vagal anti-inflammatory reflexes, enteric neurons, sensory neurons, enteric glia, macrophages, dendritic cells, T cells, innate lymphoid cells, mast cells, and neutrophils. Therapeutic opportunities include diet, prebiotics, probiotics, postbiotics, fecal microbiota transplantation, metabolite-based interventions, vagus nerve stimulation, neuropeptide or serotonin pathway modulation, and combination strategies with established anti-inflammatory therapies. UC-specific evidence is emphasized where available, with explicit distinction between human UC findings, broader inflammatory bowel disease (IBD) evidence, experimental colitis models, and general mechanistic studies. A microbiota–neuroimmune framework may help move UC research beyond descriptive dysbiosis toward mechanism-guided precision therapy; however, most causal neuroimmune pathways still require validation in well-phenotyped human UC cohorts, and the proposed endotypes in this review are hypothesis-generating and require prospective validation.