Pyruvate is modified by tea/coffee metabolites and reversely correlated with multiple system atrophy and Parkinson's disease
Xu-Ying Li,
Teng Xue,
Hong Lai,
Jing Dai,
Fangda Peng,
Fanxi Xu,
Junge Zhu,
Xian Li,
Junya Hu,
Wei Li,
Raoli He,
Lina Chen,
Ying Chen,
Chunguang Ding,
Guoguang Zhao,
Xianyang Chen,
Qinyong Ye,
Zhiheng Xu,
Chaodong Wang
Affiliations
Xu-Ying Li
Department of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China
Teng Xue
Zhongyuanborui Key Laboratory of Genetics and Metabolism, Guangdong-Macao In-depth Cooperation Zone in Hengqin, China; Zhongguancun Biological and Medical Big Data Center, Beijing, China
Hong Lai
Department of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China
Jing Dai
National Center for Occupational Safety and Health, NHC (National Center for Occupational Medicine of Coal Industry), Beijing, China
Fangda Peng
National Center for Occupational Safety and Health, NHC (National Center for Occupational Medicine of Coal Industry), Beijing, China
Fanxi Xu
Department of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China
Junge Zhu
Department of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China
Xian Li
Department of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China
Junya Hu
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
Wei Li
Department of Neurobiology, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China
Raoli He
Department of Neurology, Fujian Medical University Union Hospital, Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
Lina Chen
Department of Neurology, Fujian Medical University Union Hospital, Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
Ying Chen
Department of Neurology, Fujian Medical University Union Hospital, Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China
Chunguang Ding
National Center for Occupational Safety and Health, NHC (National Center for Occupational Medicine of Coal Industry), Beijing, China
Guoguang Zhao
Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, Clinical Research Center for Epilepsy Capital Medical University, Beijing, China
Xianyang Chen
Zhongguancun Biological and Medical Big Data Center, Beijing, China; Bao Feng Key Laboratory of Genetics and Metabolism, Beijing, China; Corresponding author. Bao Feng Key Laboratory of Genetics and Metabolism, Beijing, China
Qinyong Ye
Department of Neurology, Fujian Medical University Union Hospital, Institute of Neuroscience, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China; Corresponding author.
Zhiheng Xu
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China; Corresponding author.
Chaodong Wang
Department of Neurology and Neurobiology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, China; Corresponding author.
Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.
