Abstract

The gut mucin specialist Akkermansia muciniphila (A. muciniphila) exhibits a paradoxical duality in PD, showing both positive and negative correlations with motor and non-motor symptoms across distinct PD subtypes. This enigmatic role is further complicated by its dynamic lifespan trajectory: colonizing early life, peaking in adulthood, declining with aging, yet resurging in longevity cohorts. This review synthesizes evidence on A. muciniphila’s structural components, its divergent associations with PD phenotypes, and the dietary and host factors shaping its abundance from gestation to senescence. We propose a lifespan-targeted intervention model that strategically modulates A. muciniphila, which could concurrently mitigate PD progression and promote healthy aging. We suggest suppressing its neurotoxic pathways in susceptible individuals while enhancing its beneficial functions in the aging process. Reconciling this microbial Janus face may pave the way for novel microbiome-based precision therapeutics against neurodegeneration.

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