Akkermansia muciniphila protects against dopamine neurotoxicity by modulating butyrate to inhibit microglia-mediated neuroinflammation.

Parkinson's disease (PD) is an age-related and second most common neurodegenerative disease. To date, safe and efficient therapeutic drugs are deficient. In recent years, the relationship between gut microbiota and CNS have received more attention. Homeostatic imbalance of gut microbiota was revealed to participate in the progression of PD. This study detected that Akkermansia muciniphila (A. muciniphila) was apparently decreased in the feces of PD rats via 16S rRNA amplicon sequencing. Furtherly, we found that exogenous supplementation of A. muciniphila could improve 6-OHDA-induced motor dysfunction and dopamine (DA) neuronal damage and neuroinflammatory factors release in PD rats. Moreover, the short-chain fatty acids (SCFAs) sequencing demonstrated that A. muciniphila addition increased butyrate content both in gut and brain. The subsequent functional experiments confirmed that the exogenous supplementation of butyrate conferred neuroprotection against DA neurotoxicity. Mechanically, butyrate targeted microglia to attenuate DA neuronal injury via inhibiting microglia activation and neuroinflammatory factors production. In conclusion, A. muciniphila protected DA neuronal damage by modulating butyrate to inhibit microglia-elicited neuroinflammation. These findings provided a potential application of A. muciniphila on PD treatment.