Gut microbiota-associated taurine metabolism dysregulation in a mouse model of Parkinson’s disease

Abstract

ABSTRACT Parkinson’s disease (PD) is recognized as a multisystem disease concerning gastrointestinal (GI) dysfunction and microbiota dysbiosis. However, the mechanism by which microbial dysbiosis contributes to pathogenesis of PD and the relationship between gut microbes and metabolites remain to be deeply elucidated. This study aims to explore the altered microflora and serum metabolites in PD mice and their role in PD etiology. Herein, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) was injected intraperitoneally to establish the PD mice model. 16S rRNA sequencing and ultrahigh-performance liquid chromatography coupled with Q Exactive HF-X mass spectrometry were used to depict the profile of gut bacteria and metabolites. Phylogenetic investigation of communities by reconstruction of unobserved states 2 analysis was performed to elucidate the functional link between the microbe-metabolite axis and PD. We confirmed the MPTP-induced dopaminergic (DA) neuron loss accompanied by the GI dysfunction. Higher abundances of Aerococcus , Staphylococcus , and Ruminococcaceae , and lower abundances of Lactobacillus , Lachnospiraceae , and Adlercreutzia were identified in PD mice. Meanwhile, the differential metabolites concerning “taurine and hypotaurine metabolism” were markedly downregulated in PD mice. Furthermore, Lactobacillus , Adlercreutzia , and taurine-related metabolites showed the most significant correlation with pathological and GI performance of PD mice. The abundances of microbial transporter and enzymes participating in the degeneration of taurine were disturbed in PD mice. More importantly, taurine supplement is protected from MPTP-induced motor deficits and DA neuron loss. The detection of disturbed taurine metabolism in PD mice suggests a mechanism whereby dysregulation of the microbiota-metabolism axis contributes to the etiology of MPTP-treated mice. IMPORTANCE PD is recognized as a multisystem disease concerning GI dysfunction and microbiota dysbiosis but still lacks ideal therapies. Recently, aberrant microbiota-derived metabolites are emerging as important participants in PD etiology. However, the alterations of gut microbiota community and serum untargeted metabolite profile have not been fully investigated in a PD mice model. Here, we discover sharply reduced levels of Lactobacillus and taurine in MPTP-treated mice. Moreover, Lactobacillus , Adlercreutzia , and taurine-related metabolites showed the most significant correlation with pathological and GI performance of PD mice. The abundances of microbial transporter and enzymes participating in the degeneration of taurine were disturbed in PD mice. Most importantly, taurine supplement ameliorates MPTP-induced motor deficits, DA neuron loss, and microglial activation. Our data highlight the impaired taurine-based microbiome-metabolism axis during the progression of PD and reveal a novel and previously unrecognized role of genera in modulating taurine metabolism.