Oral pathogens exacerbate Parkinson’s disease by promoting Th1 cell infiltration in mice

Author:

Bai Xue-Bing,Xu Shuo,Zhou Lu-Jun,Meng Xiao-Qian,Li Yu-Lin,Chen Yan-Lin,Jiang Yi-Han,Lin Wen-Zhen,Chen Bo-Yan,Du Lin-Juan,Tian Guo-Cai,Liu Yan,Duan Sheng-Zhong,Zhu Ya-Qin

Abstract

Abstract Background Parkinson’s disease (PD) is a common chronic neurological disorder with a high risk of disability and no cure. Periodontitis is an infectious bacterial disease occurring in periodontal supporting tissues. Studies have shown that periodontitis is closely related to PD. However, direct evidence of the effect of periodontitis on PD is lacking. Here, we demonstrated that ligature-induced periodontitis with application of subgingival plaque (LIP-SP) exacerbated motor dysfunction, microglial activation, and dopaminergic neuron loss in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. Results The 16S rRNA gene sequencing revealed that LIP-SP induced oral and gut dysbiosis. Particularly, Veillonella parvula (V. parvula) and Streptococcus mutans (S. mutans) from oral ligatures were increased in the fecal samples of MPTP + LIP-SP treated mice. We further demonstrated that V. parvula and S. mutans played crucial roles in LIP-SP mediated exacerbation of motor dysfunction and neurodegeneration in PD mice. V. parvula and S. mutans caused microglial activation in the brain, as well as T helper 1 (Th1) cells infiltration in the brain, cervical lymph nodes, ileum and colon in PD mice. Moreover, we observed a protective effect of IFNγ neutralization on dopaminergic neurons in V. parvula- and S. mutans-treated PD mice. Conclusions Our study demonstrates that oral pathogens V. parvula and S. mutans necessitate the existence of periodontitis to exacerbate motor dysfunction and neurodegeneration in MPTP-induced PD mice. The underlying mechanisms include alterations of oral and gut microbiota, along with immune activation in both brain and peripheral regions.

Funder

National Natural Science Foundation of China

Shanghai Clinical Research Center for Oral Diseases

Shanghai Municipal Key Clinical Specialty

Shanghai’s Top Priority Research Center

The innovative research team of high-level local universities in Shanghai

The research discipline fund from Ninth People’s Hospital

Publisher

Springer Science and Business Media LLC

Subject

Microbiology (medical),Microbiology

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