Neuroprotective effects of hypoactive <i>Akkermansia muciniphila</i> in MPTP-induced mouse models of Parkinson’s disease

Parkinson's disease (PD) has been associated with the microbiota-gut-brain axis, and probiotics have been shown to alleviate PD symptoms via various mechanisms. <i>Akkermansia muciniphila</i> has demonstrated therapeutic effects in some neurological disorders; however, its role in PD treatment remains debated. This study revealed that orally administered hypoactive <i>Akkermansia muciniphila</i> inhibited dopaminergic neuron loss in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Its ingestion also reduced astrocyte activation and mitigated inflammatory responses in both the brain and colon. Additionally, hypoactive <i>Akkermansia muciniphila</i> modulated intestinal microbiota composition in PD model mice. These findings suggest that hypoactive <i>Akkermansia muciniphila</i> reduces neurotoxicity in an MPTP-induced PD model and may offer potential for inhibiting PD progression.IMPORTANCERecent research suggests a connection between Parkinson's disease (PD) and the microbiota-gut-brain axis, with evidence indicating that probiotics may alleviate PD symptoms. Although <i>Akkermansia muciniphila</i> has demonstrated potential benefits for certain neurological disorders, its efficacy in the treatment of PD is still a subject of ongoing debate. Here, we demonstrated that hypoactive <i>Akkermansia muciniphila</i> ameliorated dopaminergic neuronal death, correlating to the reduction of glial hyperactivation and neuroinflammation. Hypoactive <i>Akkermansia muciniphila</i> also induced microbiota fluctuation, which may perform a sophisticated effect on PD progression. Our study may provide an innovative strategy for using hypoactive <i>Akkermansia muciniphila</i> as a therapy or adjuvant therapy for PD.