Neuroprotective effects of hypoactive Akkermansia muciniphila 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. Akkermansia muciniphila has demonstrated therapeutic effects in some neurological disorders; however, its role in PD treatment remains debated. This study revealed that orally administered hypoactive Akkermansia muciniphila 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 Akkermansia muciniphila modulated intestinal microbiota composition in PD model mice. These findings suggest that hypoactive Akkermansia muciniphila 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 Akkermansia muciniphila 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 Akkermansia muciniphila ameliorated dopaminergic neuronal death, correlating to the reduction of glial hyperactivation and neuroinflammation. Hypoactive Akkermansia muciniphila also induced microbiota fluctuation, which may perform a sophisticated effect on PD progression. Our study may provide an innovative strategy for using hypoactive Akkermansia muciniphila as a therapy or adjuvant therapy for PD.