Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson's disease

Szu-Ju Chen; Yu-Jun Wu; Chieh-Chang Chen; Yu-Wei Wu; Jyh-Ming Liou; Ming-Shiang Wu; Ching-Hua Kuo; Chin-Hsien Lin

doi:10.1038/s41531-023-00612-y

Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson's disease

NPJ Parkinsons Dis. 2023 Dec 14;9(1):165. doi: 10.1038/s41531-023-00612-y.

Authors

Szu-Ju Chen^#^{1

2

3}, Yu-Jun Wu^#⁴, Chieh-Chang Chen^{3

5}, Yu-Wei Wu⁶, Jyh-Ming Liou⁵, Ming-Shiang Wu⁵, Ching-Hua Kuo^{7

8

9}, Chin-Hsien Lin^{10

11}

Affiliations

¹ Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan.
³ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁴ School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
⁶ Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
⁷ Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. kuoch@ntu.edu.tw.
⁸ The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan. kuoch@ntu.edu.tw.
⁹ Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. kuoch@ntu.edu.tw.
¹⁰ Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. chlin@ntu.edu.tw.
¹¹ Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. chlin@ntu.edu.tw.

^# Contributed equally.

Abstract

Gut microbial proteolytic metabolism has been reportedly altered in Parkinson's disease (PD). However, the circulating aromatic amino acids (AAA) described in PD are inconsistent. Here we aimed to investigate plasma AAA profiles in a large cohort of PD patients, and examine their correlations with clinical severity and gut microbiota changes. We enrolled 500 participants including 250 PD patients and 250 neurologically normal controls. Plasma metabolites were measured using liquid chromatography mass spectrometry. Faecal samples were newly collected from 154 PD patients for microbiota shotgun metagenomic sequencing combined with data derived from 96 PD patients reported before. Data were collected regarding diet, medications, and motor and non-motor symptoms of PD. Compared to controls, PD patients had higher plasma AAA levels, including phenylacetylglutamine (PAGln), p-cresol sulfate (Pcs), p-cresol glucuronide (Pcg), and indoxyl sulfate (IS). Multivariable linear regression analyses, with adjustment for age, sex, and medications, revealed that the plasma levels of PAGln (coefficient 4.49, 95% CI 0.40-8.58, P = 0.032) and Pcg (coefficient 1.79, 95% CI 0.07-3.52, P = 0.042) positively correlated with motor symptom severity but not cognitive function. After correcting for abovementioned potential confounders, these AAA metabolites were also associated with the occurrence of constipation in PD patients (all P < 0.05). Furthermore, plasma levels of AAA metabolites were correlated with the abundance of specific gut microbiota species, including Bacteroides sp. CF01-10NS, Bacteroides vulgatus, and Clostridium sp. AF50-3. In conclusion, elevated plasma AAA metabolite levels correlated with disease characteristics in PD, suggesting that upregulated proteolytic metabolism may contribute to the pathophysiology of PD.

Abstract

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