The Emerging Role of Peripheral Anti-Inflammatory Agents in Modulating Neurodegenerative Pathology: A Cross-Domain Review

Abstract

Neurodegenerative diseases are increasingly recognized as complex, multisystem disorders involving dynamic interactions among the gut microbiota, peripheral immune system, and central nervous system. Emerging evidence suggests that alterations in gut microbial composition and chronic peripheral inflammation actively contribute to neurodegeneration. The gut-brain axis integrates environmental, genetic, and metabolic factors, with the microbiota acting as a key regulator of neuroinflammation and blood–brain barrier integrity. This review synthesizes recent advances in understanding how peripheral immunity and gut microbiota influence neurodegenerative processes, highlighting key signaling pathways and mechanisms. It further examines current therapeutic strategies— including dietary modulation, probiotics, prebiotics, and fecal microbiota transplantation— and discusses translational challenges and opportunities. Moving forward, elucidating causal relationships within the gut-brain-immune network and developing precision, systems-level interventions will be critical for transforming the prevention, diagnosis, and treatment of neurodegenerative diseases.