Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease
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 correlatio...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-023-00612-y |
| _version_ | 1797388448392282112 |
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| author | Szu-Ju Chen Yu-Jun Wu Chieh-Chang Chen Yu-Wei Wu Jyh-Ming Liou Ming-Shiang Wu Ching-Hua Kuo Chin-Hsien Lin |
| author_facet | Szu-Ju Chen Yu-Jun Wu Chieh-Chang Chen Yu-Wei Wu Jyh-Ming Liou Ming-Shiang Wu Ching-Hua Kuo Chin-Hsien Lin |
| author_sort | Szu-Ju Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T22:40:00Z |
| format | Article |
| id | doaj.art-053520382839446b81f4159e5a8be27c |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-08T22:40:00Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-053520382839446b81f4159e5a8be27c2023-12-17T12:10:43ZengNature Portfolionpj Parkinson's Disease2373-80572023-12-019111010.1038/s41531-023-00612-yPlasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s diseaseSzu-Ju Chen0Yu-Jun Wu1Chieh-Chang Chen2Yu-Wei Wu3Jyh-Ming Liou4Ming-Shiang Wu5Ching-Hua Kuo6Chin-Hsien Lin7Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan UniversitySchool of Pharmacy, College of Medicine, National Taiwan UniversityGraduate Institute of Clinical Medicine, College of Medicine, National Taiwan UniversityGraduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical UniversityDivision of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan UniversityDivision of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan UniversityGraduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical UniversityDepartment of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan UniversityAbstract 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.https://doi.org/10.1038/s41531-023-00612-y |
| spellingShingle | Szu-Ju Chen Yu-Jun Wu Chieh-Chang Chen Yu-Wei Wu Jyh-Ming Liou Ming-Shiang Wu Ching-Hua Kuo Chin-Hsien Lin Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease npj Parkinson's Disease |
| title | Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease |
| title_full | Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease |
| title_fullStr | Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease |
| title_full_unstemmed | Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease |
| title_short | Plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of Parkinson’s disease |
| title_sort | plasma metabolites of aromatic amino acids associate with clinical severity and gut microbiota of parkinson s disease |
| url | https://doi.org/10.1038/s41531-023-00612-y |
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