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. 2019 Jun:44:691-707.
doi: 10.1016/j.ebiom.2019.05.064. Epub 2019 Jun 18.

Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression

Velma T E Aho  1 , Pedro A B Pereira  1 , Sari Voutilainen  2 , Lars Paulin  3 , Eero Pekkonen  4 , Petri Auvinen  3 , Filip Scheperjans  5
Affiliations

Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression

Velma T E Aho et al. EBioMedicine. 2019 Jun.

Abstract

Background: Several publications have described differences in cross-sectional comparisons of gut microbiota between patients with Parkinson's disease and control subjects, with considerable variability of the reported differentially abundant taxa. The temporal stability of such microbiota alterations and their relationship to disease progression have not been previously studied with a high-throughput sequencing based approach.

Methods: We collected clinical data and stool samples from 64 Parkinson's patients and 64 control subjects twice, on average 2·25 years apart. Disease progression was evaluated based on changes in Unified Parkinson's Disease Rating Scale and Levodopa Equivalent Dose, and microbiota were characterized with 16S rRNA gene amplicon sequencing.

Findings: We compared patients to controls, and patients with stable disease to those with faster progression. There were significant differences between microbial communities of patients and controls when corrected for confounders, but not between timepoints. Specific bacterial taxa that differed between patients and controls at both timepoints included several previously reported ones, such as Roseburia, Prevotella and Bifidobacterium. In progression comparisons, differentially abundant taxa were inconsistent across methods and timepoints, but there was some support for a different distribution of enterotypes and a decreased abundance of Prevotella in faster-progressing patients.

Interpretation: The previously detected gut microbiota differences between Parkinson's patients and controls persisted after 2 years. While we found some evidence for a connection between microbiota and disease progression, a longer follow-up period is required to confirm these findings.

Keywords: Disease progression; Gut microbiota; Gut-brain-axis; Parkinson's disease.

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Figures

Fig. 1
Fig. 1
NMDS ordination of samples excluded as microbiome outliers.
Fig. 2
Fig. 2
Histogram of the progression variable based on change in UPDRS I-III and LED. Legend: Solid vertical line represents the median, dashed vertical line represents the 3rd quartile, which was used to categorize subjects into “stable” and “progressed”.
Fig. 3
Fig. 3
Biplot of principal component analysis of diet data, showing principal components 1 and 3. Legend: A. Component loadings; B. PD patients and controls, with 90% confidence ellipses.
Fig. 4
Fig. 4
10 most common bacterial families at each timepoint. Legend: A. All study subjects by PD status; B. PD patients by progression status.
Fig. 5
Fig. 5
Distributions of enterotypes in the subject groups. Legend: Showing control subjects and PD patients classified by progression (excluding PD patients without a progression classification).
Fig. 6
Fig. 6
Interactions in linear regression of alpha diversity, PD status and confounders. Legend: A. Shannon index and BMI; B. Inverse Simpson index and BMI, C. Observed richness and Victoria Bowel Performance Scale.
Fig. 7
Fig. 7
NMDS ordination illustrating microbial community differences between PD patients and control subjects. Legend: Also showing centroid locations for microbial genera reported as differentially abundant between the two groups in previous studies.
Fig. 8
Fig. 8
Genus-level NMDS ordination plots of the main confounding variables. Legend: A. BMI, diet and Rome III score; B. Calcium channel blockers (CCB) medication; C. ACE-I/ARB medication.
Fig. 9
Fig. 9
Differentially abundant taxa between control subjects and PD patients according to three different tools. Legend: A. Baseline; B. Follow-up.
Fig. 10
Fig. 10
Genera and families that differ significantly between control subjects and PD patients. Legend: Showing taxa that differ at either timepoint according to more than one method, or have been reported as differing in a previous publication and have p < 0.1 at one timepoint according to at least one method.
Fig. 11
Fig. 11
Genera and families that differ significantly between stable and progressed PD patients. Legend: Showing taxa that differ at one timepoint according to more than one method, or at both timepoints according to a single method.
See this image and copyright information in PMC

References

    1. Mertsalmi T.H., Aho V.T.E., Pereira P.A.B. More than constipation – bowel symptoms in Parkinson's disease and their connection to gut microbiota. Eur. J. Neurol. 2017;24(11):1375–1383. - PubMed
    2. Mertsalmi TH, Aho VTE, Pereira PAB, et al. More than constipation – bowel symptoms in Parkinson's disease and their connection to gut microbiota. Eur J Neurol 2017; 24(11): 1375–83. doi:10.1111/ene.13398. - PubMed
    1. Fasano A., Visanji N.P., Liu L.W.C., Lang A.E., Pfeiffer R.F. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol. 2015;14(6):625–639. - PubMed
    2. Fasano A, Visanji NP, Liu LWC, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol 2015; 14(6): 625–39. doi:10.1016/S1474-4422(15)00007-1. - PubMed
    1. Hawkes C.H., Del Tredici K., Braak H. Parkinson's disease: a dual-hit hypothesis. Neuropathol. Appl. Neurobiol. 2007;33(6):599–614. - PMC - PubMed
    2. Hawkes CH, Del Tredici K, Braak H. Parkinson's disease: a dual-hit hypothesis. Neuropathol Appl Neurobiol 2007; 33(6): 599–614. doi:10.1111/j.1365-2990.2007.00874.x. - PMC - PubMed
    1. Pereira P.A.B., Aho V.T.E., Paulin L., Pekkonen E., Auvinen P., Scheperjans F. Oral and nasal microbiota in Parkinson's disease. Parkinsonism Relat. Disord. 2017;38:61–67. - PubMed
    2. Pereira PAB, Aho VTE, Paulin L, Pekkonen E, Auvinen P, Scheperjans F. Oral and nasal microbiota in Parkinson's disease. Parkinsonism Relat Disord 2017; 38: 61–7. - PubMed
    1. Heintz-Buschart A., Pandey U., Wicke T. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. Mov. Disord. 2018;33(1):88–98. - PMC - PubMed
    2. Heintz-Buschart A, Pandey U, Wicke T, et al. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord 2018; 33(1): 88–98. doi:10.1002/mds.27105. - PMC - PubMed

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