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Cited by 269Gut microbiota and healthParkinson's Disease Mechanisms and TreatmentsGastrointestinal motility and disorders

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Association of Fecal and Plasma Levels of Short-Chain Fatty Acids With Gut Microbiota and Clinical Severity in Patients With Parkinson Disease

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Chen, Szu-Ju, Chen, Chieh-Chang, Liao, Hsin-Yu, Lin, Ya-Ting, Wu, Yu-Wei, Liou, Jyh-Ming, Wu, Ming-Shiang, Kuo, Ching-Hua, Lin, Chin-Hsien·2022·Neurology
DOI 10.1212/wnl.0000000000013225PMC PMC8883514
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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 Parkinson9s 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.

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Crossref · 10.1212/wnl.0000000000013225

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Figures

Figure 1 Comparison of Fecal Levels of Short Chain Fatty Acids in Patients With PD and Healthy Controls Violin plot shows data density and median with interquartile range (solid and dashed horizontal lines) for fecal levels of acetic acid (A), propionic acid (B), butyric acid (C), and valeric acid (D) in patients with Parkinson disease (PD) and unaffected controls. Mean ± SD (solid horizontal line, dashed horizontal line) is shown. *p < 0.05, **p < 0.01.
Figure 1 Comparison of Fecal Levels of Short Chain Fatty Acids in Patients With PD and Healthy Controls Violin plot shows data density and median with interquartile range (solid and dashed horizontal lines) for fecal levels of acetic acid (A), propionic acid (B), butyric acid (C), and valeric acid (D) in patients with Parkinson disease (PD) and unaffected controls. Mean ± SD (solid horizontal line, dashed horizontal line) is shown. *p < 0.05, **p < 0.01.CC BY-NC-ND · PubMed Central
Figure 2 Comparison of Plasma Concentrations of Short Chain Fatty Acids in Patients With PD and Healthy Controls Violin plot shows data density and median with interquartile range (solid and dashed horizontal lines) for plasma concentrations of acetic acid (A), propionic acid (B), butyric acid (C), and valeric acid (D) in patients with Parkinson disease (PD) and unaffected controls. Mean ± SD (solid horizontal line, dashed horizontal line) is shown. *p < 0.05, **p < 0.01.
Figure 2 Comparison of Plasma Concentrations of Short Chain Fatty Acids in Patients With PD and Healthy Controls Violin plot shows data density and median with interquartile range (solid and dashed horizontal lines) for plasma concentrations of acetic acid (A), propionic acid (B), butyric acid (C), and valeric acid (D) in patients with Parkinson disease (PD) and unaffected controls. Mean ± SD (solid horizontal line, dashed horizontal line) is shown. *p < 0.05, **p < 0.01.CC BY-NC-ND · PubMed Central
Figure 3 ROC Curves for Distinguishing Patients With PD From Controls and Correlations Between SCFA Levels and Clinical Motor Symptom Severity in Patients With PD (A) The accuracy of estimating Parkinson disease (PD) using age and sex alone (area under the curve [AUC] = 0.55, p = 0.357) significantly improved with the addition of fecal levels of acetic acid, propionic acid, and butyric acid, which showed differences between patients with PD and controls (AUC = 0.65, p = 0.004). The accuracy of estimating the occurrence of PD further improved in a full model incorporating both fecal and plasma levels of targeted (SCFAs), which showed differences between patients with PD and controls (AUC = 0.72, p < 0.001). (B–D) Scatterplots show negative correlations between Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor scores and fecal levels of acetic acid (B), propionic acid (C), and butyric acid (D). ROC = receiving operating characteristic.
Figure 3 ROC Curves for Distinguishing Patients With PD From Controls and Correlations Between SCFA Levels and Clinical Motor Symptom Severity in Patients With PD (A) The accuracy of estimating Parkinson disease (PD) using age and sex alone (area under the curve [AUC] = 0.55, p = 0.357) significantly improved with the addition of fecal levels of acetic acid, propionic acid, and butyric acid, which showed differences between patients with PD and controls (AUC = 0.65, p = 0.004). The accuracy of estimating the occurrence of PD further improved in a full model incorporating both fecal and plasma levels of targeted (SCFAs), which showed differences between patients with PD and controls (AUC = 0.72, p < 0.001). (B–D) Scatterplots show negative correlations between Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor scores and fecal levels of acetic acid (B), propionic acid (C), and butyric acid (D). ROC = receiving operating characteristic.CC BY-NC-ND · PubMed Central
Figure 4 Heat Maps Representing the Spearman Correlation of the Relative Abundance of Different Bacteria and the Plasma-to-Fecal Ratios of SCFAs Correlations between plasma-to-fecal ratios of different types of short-chain fatty acids (SCFAs) in patients with Parkinson disease. The r values are represented by gradient colors, where red and blue cells indicate positive and negative correlations, respectively.
Figure 4 Heat Maps Representing the Spearman Correlation of the Relative Abundance of Different Bacteria and the Plasma-to-Fecal Ratios of SCFAs Correlations between plasma-to-fecal ratios of different types of short-chain fatty acids (SCFAs) in patients with Parkinson disease. The r values are represented by gradient colors, where red and blue cells indicate positive and negative correlations, respectively.CC BY-NC-ND · PubMed Central

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  1. Team RC. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2020.

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Metadata

Authors
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.
Affiliations
National Taiwan University Hospital (TW)
Corresponding author
  • Lin, Ya-Ting
  • Lin, Chin-Hsien
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2022-02-22
Volume
98
Issue
8
Pages
e848-e858
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000013225
PMC
PMC8883514
OpenAlex
W4206517428
Cited by
269
References
48
Citations by year
2026: 50 · 2025: 82 · 2024: 59 · 2023: 41 · 2022: 37
FWCI
17.88
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Neurology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • University of New South Wales
  • National Health Research Institutes
  • National Taiwan University Hospital
  • National Taiwan University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
Parkinson's disease, short-chain fatty acids, gut microbiota, fecal SCFA, butyrate, propionate, acetate, valerate, motor impairment, cognitive impairment, Ruminococcus, SCFA-producing bacteria, gut-brain axis, disease severity markers, dietary fiber
MeSH terms
Gastrointestinal Microbiome, Fatty Acids, Volatile, Feces, Humans, Parkinson Disease, Cohort Studies

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