Gut-Meningeal Immunity: A Missing Link in Neuroinflammatory Disorders

Traditionally considered immune-privileged, the central nervous system (CNS) is now recognised as immunologically dynamic, with the meninges serving as a key interface for immune surveillance and neuroimmune communication. Recent advances support the emerging concept of a gut-meningeal immune axis, wherein the gut microbiota may influence meningeal immunity, through the recruitment of gut-educated immune cells and other microbiota-dependent signals, although the mechanisms involved remain incompletely understood. Notably, the neonatal period represents a critical window of immune and microbial development, during which dysbiosis can disrupt microglia maturation, cytokine balance, and long-term neuroimmune resilience. Here, we review the structural and immunological properties of the meninges, the mechanisms potentially linking the gut microbiota to meningeal immunity, and the role of this emerging axis in neuroinflammatory diseases. We further explore the developmental implications of early-life microbial disturbances and discuss the therapeutic potential of microbiota-targeted interventions to modulate meningeal immunity and mitigate CNS pathology.