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The impact of device-assisted therapies on the gut microbiome in Parkinson’s disease

Abstract

Background

Microbiome feedbacks are proposed to influence Parkinson’s disease (PD) pathophysiology. A number of studies have evaluated the impact of oral medication on the gut microbiome (GM) in PD. However, the influence of PD device-assisted therapies (DATs) on the GM remains to be investigated.

Objectives

To profile acute gut microbial community alterations in response to PD DAT initiation.

Methods

Clinical data and stool samples were collected from 21 PD patients initiating either deep brain stimulation (DBS) or levodopa–carbidopa intestinal gel (LCIG) and ten spousal healthy control (HC) subjects. 16S amplicon sequencing of stool DNA enabled comparison of temporal GM stability between groups and with clinical measures, including disease alterations relative to therapy initiation.

Results

We assessed GM response to therapy in the PD group by comparing pre-therapy (− 2 and 0 weeks) with post-therapy initiation timepoints (+ 2 and + 4 weeks) and HCs at baseline (0 weeks). Altered GM compositions were noted between the PD and HC groups at various taxonomic levels, including specific differences for DBS (overrepresentation of Clostridium_XlVa, Bilophila, Parabacteroides, Pseudoflavonifractor and underrepresentation of Dorea) and LCIG therapy (overrepresentation of Pseudoflavonifractor, Escherichia/Shigella, and underrepresentation of Gemmiger). Beta diversity changes were also found over the 4 week post-treatment initiation period.

Conclusions

We report on initial short-term GM changes in response to the initiation of PD DATs. Prior to the introduction of the DAT, a PD-associated GM was observed. Following initiation of DAT, several DAT-specific changes in GM composition were identified, suggesting DATs can influence the GM in PD.

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Availability of data and material

Upon request from authors.

Code availability

Custom code available at https://github.com/SydneyBioX/microbiome-PD

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Acknowledgements

We thank Parkinson’s New South Wales for a Research Seed Grant to ML, CMS and RLD. Professor Vicki Flood and Mr Jon Flood for assistance analysing and interpreting the Food Frequency Questionnaire data. We would also like to sincerely thank all our participants for their patience and willingness to contribute to this research. ML is the recipient of a RACP Research Entry Scholarship and Northern Precinct Ramsay Scholarship. RLD was a New South Wales Health Early-Mid Career Research Fellow. CMS is a NHMRC Practitioner Fellow (APP1136800). This work is also supported by the Australian Research Council Discovery Project grant (DP170100654) for JYHY and XX.

Funding

Not industry sponsored. Supported by a Parkinson’s New South Wales, Research Seed Grant.

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Authors and Affiliations

Authors

Contributions

ML: conceived and designed the study, recruited and examined all participants, collected, generated and analysed the data, drafted and reviewed the manuscript. XX: analysed the genomic and clinical data, drafted and reviewed the manuscript. AJH: designed the study, analysed data, drafted and reviewed the manuscript. JYHY: designed the genomic and clinical analysis, drafted and reviewed the manuscript. CMS: conceived and designed the study, drafted and reviewed the manuscript. RLD: conceived and designed the study, generated data, drafted and reviewed the manuscript.

Corresponding author

Correspondence to Michal Lubomski.

Ethics declarations

Conflicts of interest

ML, XX, AJH, JYHY, CMS, RLD declare no conflicting/competing of interests.

Ethics approval

Ethical approval was granted by the Northern Sydney Local Health District Human Research Ethics Committee (HREC/18/HAWKE/109) and the North Shore Private Hospital ethics committee (NSPHEC 2018-LNR-009) and all participants provided written informed consent.

Consent to participate

All participants provided written informed consent.

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All authors provide consent for publication.

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Lubomski, M., Xu, X., Holmes, A.J. et al. The impact of device-assisted therapies on the gut microbiome in Parkinson’s disease. J Neurol 269, 780–795 (2022). https://doi.org/10.1007/s00415-021-10657-9

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  • DOI: https://doi.org/10.1007/s00415-021-10657-9

Keywords

  • Parkinson’s disease
  • Gut microbiota
  • Gastrointestinal microbiome
  • Device-assisted therapies
  • Levodopa–carbidopa intestinal gel (LCIG)
  • Deep brain stimulation (DBS)