Reframing the Gut-Brain Axis: The Gut Wall as a Neural Immune Interface in Multiple Sclerosis and Autoimmune Neurological Diseases.

Gut wall physiology in multiple sclerosis (MS) and autoimmune neurologic diseases remains underexplored. This review examines gut wall dysfunctions' contribution to MS and autoimmune neurological disorder pathogenesis and progression. We discuss 3 inter-related aspects of gut physiology: intestinal barrier, enteric nervous system (ENS), and mucosal immunity. We highlight the ENS as a putative target of immune injury in selected antibody-mediated and T cell-associated neurologic diseases. Finally, we propose a unifying framework in which the gut functions as a site of immune priming and target of autoimmune injury, bridging microbiome-driven mechanisms in MS with ENS-directed autoimmunity across neurologic diseases. ANN NEUROL 2026.