Tags

Type your tag names separated by a space and hit enter

Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease.
Neurology. 2022 02 22; 98(8):e848-e858.Neur

Abstract

BACKGROUND AND OBJECTIVES

Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson disease (PD), but fecal levels of SCFAs in patients with PD are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their interrelationships with the PD disease process, are scarce. We aimed to compare fecal and plasma levels of different SCFA subtypes in patients with PD and healthy controls to delineate their interrelations and link to gut microbiota changes and clinical severity of PD.

METHODS

A cohort of 96 patients with PD and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concentrations of SCFAs were measured using chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical comorbidities were evaluated and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE).

RESULTS

Compared with controls, patients with PD had lower fecal but higher plasma concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ = 0.26, p = 0.042) in patients with PD. MMSE scores negatively correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs in healthy controls but revealed no association in patients with PD. In the PD patient group, the abundance of proinflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid.

DISCUSSION

Reductions in fecal SCFAs but increased plasma SCFAs were observed in patients with PD and corelated to specific gut microbiota changes and the clinical severity of PD.

CLASSIFICATION OF EVIDENCE

This study provides Class III evidence that gut metabolite SCFAs distinguish between patients with PD and controls and are associated with disease severity in patients with PD.

Links

PMC Free PDF

Authors+Show Affiliations

Chen SJ
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan.
Chen CC
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan.
Liao HY
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan.
Lin YT
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan. kuoch@ntu.edu.tw q93421022@ntu.edu.tw.
Wu YW
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan.
Liou JM
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan.
Wu MS
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan.
Kuo CH
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan.
Lin CH
From the Department of Neurology (S.-J.C., C.-H.L.) and Division of Gastroenterology and Hepatology, Department of Internal Medicine (C.-C.C., J-.M.L., M.-S.W.), College of Medicine, and Department of Pharmacy (C.-H.K.), National Taiwan University Hospital, and Graduate Institute of Clinical Medicine (S.-J.C., C.-C.C.), School of Pharmacy (H.-Y.L., Y.-T.L., C.-H.K.), College of Medicine, and The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine (C.-H.K.), National Taiwan University, Taipei; Department of Neurology (S.-J.C.), National Taiwan University Hospital Bei-Hu Branch; and Graduate Institute of Biomedical Informatics, College of Medical Science and Technology (Y.-W.W.), Taipei Medical University, Taiwan. kuoch@ntu.edu.tw q93421022@ntu.edu.tw.

MeSH

Cohort StudiesFatty Acids, VolatileFecesGastrointestinal MicrobiomeHumansParkinson Disease

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34996879

Citation

Chen, Szu-Ju, et al. "Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease." Neurology, vol. 98, no. 8, 2022, pp. e848-e858.
Chen SJ, Chen CC, Liao HY, et al. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. Neurology. 2022;98(8):e848-e858.
Chen, S. J., Chen, C. C., Liao, H. Y., Lin, Y. T., Wu, Y. W., Liou, J. M., Wu, M. S., Kuo, C. H., & Lin, C. H. (2022). Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. Neurology, 98(8), e848-e858. https://doi.org/10.1212/WNL.0000000000013225
Chen SJ, et al. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. Neurology. 2022 02 22;98(8):e848-e858. PubMed PMID: 34996879.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease. AU - Chen,Szu-Ju, AU - Chen,Chieh-Chang, AU - Liao,Hsin-Yu, AU - Lin,Ya-Ting, AU - Wu,Yu-Wei, AU - Liou,Jyh-Ming, AU - Wu,Ming-Shiang, AU - Kuo,Ching-Hua, AU - Lin,Chin-Hsien, Y1 - 2022/01/07/ PY - 2021/06/28/received PY - 2021/11/30/accepted PY - 2022/1/9/pubmed PY - 2022/4/6/medline PY - 2022/1/8/entrez SP - e848 EP - e858 JF - Neurology JO - Neurology VL - 98 IS - 8 N2 - BACKGROUND AND OBJECTIVES: Short-chain fatty acids (SCFAs) are gut microbial metabolites that promote the disease process in a rodent model of Parkinson disease (PD), but fecal levels of SCFAs in patients with PD are reduced. Simultaneous assessments of fecal and plasma SCFA levels, and their interrelationships with the PD disease process, are scarce. We aimed to compare fecal and plasma levels of different SCFA subtypes in patients with PD and healthy controls to delineate their interrelations and link to gut microbiota changes and clinical severity of PD. METHODS: A cohort of 96 patients with PD and 85 controls were recruited from National Taiwan University Hospital. Fecal and plasma concentrations of SCFAs were measured using chromatography and mass spectrometry. Gut microbiota was analyzed using metagenomic shotgun sequencing. Body mass index and medical comorbidities were evaluated and dietary information was obtained using a food frequency questionnaire. To assess motor and cognitive impairment, we used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Mini-Mental Status Examination (MMSE). RESULTS: Compared with controls, patients with PD had lower fecal but higher plasma concentrations of acetate, propionate, and butyrate. After adjustment for age, sex, disease duration, and anti-PD medication dosage, MDS-UPDRS part III motor scores correlated with reduced fecal levels of acetate (ρ = -0.37, p = 0.012), propionate (ρ = -0.32, p = 0.036), and butyrate (ρ = -0.40, p = 0.004) and with increased plasma propionate concentrations (ρ = 0.26, p = 0.042) in patients with PD. MMSE scores negatively correlated with plasma levels of butyrate (ρ = -0.09, p = 0.027) and valerate (ρ = -0.032, p = 0.033) after adjustment for confounders. SCFAs-producing gut bacteria correlated positively with fecal levels of SCFAs in healthy controls but revealed no association in patients with PD. In the PD patient group, the abundance of proinflammatory microbes, such as Clostridiales bacterium NK3B98 and Ruminococcus sp AM07-15, significantly correlated with decreased fecal levels and increased plasma levels of SCFAs, especially propionic acid. DISCUSSION: Reductions in fecal SCFAs but increased plasma SCFAs were observed in patients with PD and corelated to specific gut microbiota changes and the clinical severity of PD. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that gut metabolite SCFAs distinguish between patients with PD and controls and are associated with disease severity in patients with PD. SN - 1526-632X UR - https://www.unboundmedicine.com/medline/citation/34996879/Association_of_Fecal_and_Plasma_Levels_of_Short_Chain_Fatty_Acids_With_Gut_Microbiota_and_Clinical_Severity_in_Patients_With_Parkinson_Disease_ DB - PRIME DP - Unbound Medicine ER -