Akkermansia muciniphila Is Beneficial to a Mouse Model of Parkinson’s Disease, via Alleviated Neuroinflammation and Promoted Neurogenesis, with Involvement of SCFAs

Abstract

Increasing evidence suggests that the gut microbiota may represent potential strategies for Parkinson’s disease (PD) treatment. Our previous research revealed a decreased abundance of Akkermansia muciniphila (Akk) in PD mice; however, whether Akk is beneficial to PD is unknown. To answer this question, the mice received MPTP intraperitoneally to construct a subacute model of PD and were then supplemented with Akk orally for 21 consecutive days. Motor function, dopaminergic neurons, neuroinflammation, and neurogenesis were examined. In addition, intestinal inflammation, and serum and fecal short-chain fatty acids (SCFAs) analyses, were assessed. We found that Akk treatment effectively inhibited the reduction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and partially improved the motor function in PD mice. Additionally, Akk markedly alleviated neuroinflammation in the striatum and hippocampus and promoted hippocampal neurogenesis. It also decreased the level of colon inflammation. Furthermore, these aforementioned changes are mainly accompanied by alterations in serum and fecal isovaleric acid levels, and lower intestinal permeability. Our research strongly suggests that Akk is a potential neuroprotective agent for PD therapy.

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy

“…The elevated abundance of bacterial phylum Alistipes is shown to be associated with fibromyalgia, a chronic medical condition that caused widespread musculoskeletal pain ( Clos-Garcia et al, 2019 ). Restoring the abundance of Akkermansia muciniphila attenuated neuroinflammation mouse model of Parkinson’s Disease and ameliorated inflammation in chronic colitis model ( Qiao et al, 2024 ; Yilmaz et al, 2024 ), suggesting that the decreased abundance of Akkermansia muciniphila might correlate well with the augmented neuroinflammation to mediate pain hypersensitivity after paclitaxel treatment. Similarly, oxaliplatin induces persistent mechanical allodynia in mice, a condition that can be completely reversed by eliminating the gut microbiota after antibiotic treatment, suggesting that the change in gut microbiota (dysbiosis) contributed to the development of CIPN induced by oxaliplatin.…”