Gut microbiota–neuroimmune crosstalk in autoimmune encephalitis: mechanistic insights and therapeutic prospects

Autoimmune encephalitis (AE) comprises a heterogeneous group of inflammatory disorders of the central nervous system mediated by autoimmune responses, involving multiple pathological processes, including autoantibody production, aberrant immune-cell activation, and persistent neuroinflammation. In recent years, accumulating evidence has suggested that the gut microbiota may represent an important regulatory interface linking host metabolism, immunity, and the nervous system. Through microbial structural components, metabolites, and secreted signals, the gut microbiota may influence peripheral immune responses, blood–brain barrier integrity, and central nervous system inflammation. Conversely, neuroimmune dysregulation may reshape the intestinal microbial environment through neuroendocrine–immune regulatory networks, thereby establishing a dynamic bidirectional relationship between the gut microbiota and the neuroimmune system. However, the mechanisms underlying gut microbiota–neuroimmune interactions in AE, particularly their potential changes across the disease course, remain incompletely understood. This review summarizes current evidence regarding AE-associated alterations in the gut microbiota and disturbances of neuroimmune homeostasis, with particular emphasis on the potential molecular mechanisms through which the gut microbiota modulates neuroimmune responses and, reciprocally, the neuroimmune system reshapes the intestinal microbial environment. Within a proposed phase-based conceptual framework encompassing disease initiation, progression, and the chronic phase, we further discuss the potential dynamic changes in gut microbiota–neuroimmune crosstalk during AE. In addition, we summarize emerging therapeutic strategies, including dietary and nutritional interventions, probiotics, modulation of microbial metabolic functions, fecal microbiota transplantation, and precision microbiome engineering, and discuss their current evidence base and translational potential. Collectively, gut microbiota–neuroimmune crosstalk provides a useful conceptual framework for understanding disease heterogeneity in AE and exploring microbiota-targeted interventions. However, direct AE-specific evidence remains limited, and many proposed mechanisms are currently supported primarily by observational studies, experimental models, or evidence extrapolated from related neuroimmune disorders. Future studies integrating longitudinal clinical cohorts, multi-omics profiling, and functional validation are needed to define key microbial functions, host immune responses, and their dynamic relationships in AE, thereby providing a stronger mechanistic foundation for future precision diagnostic and therapeutic strategies.