Seok Jong Chung1, John Hoon Rim2, Dajeong Ji3, Sangwon Lee4, Han Soo Yoo5, Jin Ho Jung5, KyoungWon Baik5, Yonghoon Choi4, Byoung Seok Ye5, Young H Sohn5, Mijin Yun4, Sang-Guk Lee6, Phil Hyu Lee7. 1. Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea; Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, South Korea. 2. Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea; Department of Medicine, Physician-Scientist Program, Yonsei University Graduate School of Medicine, Seoul, South Korea. 3. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea. 4. Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, South Korea. 5. Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea. 6. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: comforter6@yuhs.ac. 7. Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: phlee@yuhs.ac.
Abstract
OBJECTIVES: This study aimed to investigate the potential of using changes in the plasma levels of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, as a biomarker in early Parkinson's disease (PD). METHODS: Plasma TMAO levels were measured in 85 patients with drug-naïve early stage PD and 20 healthy controls. A linear mixed model was used to assess longitudinal changes in levodopa-equivalent dose (LED) during follow-up (>2 y) in three tertile PD groups according to plasma TMAO levels. Additionally, a Cox regression analysis was performed to assess the effect of plasma TMAO levels on dementia conversion. RESULTS: Plasma TMAO levels of patients with PD were lower than those of healthy controls. A linear mixed model demonstrated that patients with PD and lower levels of TMAO (<4.75 μmol/L; i.e., lowest tertile group) exhibited faster increases in LED over time. The Cox regression model did not reveal that plasma TMAO level was associated with the risk for dementia conversion (P = 0.488). However, when we divided patients with PD into two subgroups according to bet cutoff TMAO level to maximize the log-rank statistics, the PD group with a low plasma TMAO level (<6.92 μmol/L) had a higher risk (with borderline statistical significance) for PD-dementia conversion than the group with a high TMAO level (hazard ratio: 7.565; 95% confidence interval, 1.004-57.019; P = 0.050). CONCLUSIONS: The results demonstrate that lower baseline plasma TMAO levels are associated with faster increases in LED and tend to increase the risk for PD-dementia conversion, suggesting the prognostic implications of TMAO in early stage PD.
OBJECTIVES: This study aimed to investigate the potential of using changes in the plasma levels of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, as a biomarker in early Parkinson's disease (PD). METHODS: Plasma TMAO levels were measured in 85 patients with drug-naïve early stage PD and 20 healthy controls. A linear mixed model was used to assess longitudinal changes in levodopa-equivalent dose (LED) during follow-up (>2 y) in three tertile PD groups according to plasma TMAO levels. Additionally, a Cox regression analysis was performed to assess the effect of plasma TMAO levels on dementia conversion. RESULTS: Plasma TMAO levels of patients with PD were lower than those of healthy controls. A linear mixed model demonstrated that patients with PD and lower levels of TMAO (<4.75 μmol/L; i.e., lowest tertile group) exhibited faster increases in LED over time. The Cox regression model did not reveal that plasma TMAO level was associated with the risk for dementia conversion (P = 0.488). However, when we divided patients with PD into two subgroups according to bet cutoff TMAO level to maximize the log-rank statistics, the PD group with a low plasma TMAO level (<6.92 μmol/L) had a higher risk (with borderline statistical significance) for PD-dementia conversion than the group with a high TMAO level (hazard ratio: 7.565; 95% confidence interval, 1.004-57.019; P = 0.050). CONCLUSIONS: The results demonstrate that lower baseline plasma TMAO levels are associated with faster increases in LED and tend to increase the risk for PD-dementia conversion, suggesting the prognostic implications of TMAO in early stage PD.
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