Akkermansia muciniphila in Central Nervous System Disorders:Mechanisms, Controversies, and Therapeutic Potential

Akkermansia muciniphila (A. muciniphila) is an intestinal mucus-dwelling mucindegrading bacterium that has recently attracted great interest due to its involvement in several metabolic diseases, including obesity, diabetes, and non-alcoholic fatty liver disease. Recent findings have indicated that A. muciniphila plays an important role in central nervous system (CNS) disorders via the microbiota-gut-brain axis (MGBA). This review highlights its dual roles in neuroprotection and pathogenesis, focusing on three key mechanisms, including immunomodulation, metabolic regulation, and barrier reinforcement. Although A. muciniphila has a beneficial role in the treatment of Alzheimer's disease, stroke, and depression, it is controversial for multiple sclerosis and Parkinson's disease because of context-dependent effects. We herein summarize recent progress in an understanding of the complex interplay between A. muciniphila and CNS disorders, highlighting that more work is needed to elucidate this relationship's causality and applicability toward treatment. Finally, we discuss the potential of A. muciniphila as a diagnostic biomarker and a target for nextgeneration probiotics in CNS disease management.