Tan, Ai Huey and Chong, Chun Wie and Lim, Shen-Yang and Yap, Ivan Kok Seng and Teh, Cindy Shuan Ju and Loke, Mun Fai and Song, Sze-Looi and Tan, Jiun Yan and Ang, Ban Hong and Tan, Yong Qi and Kho, Mee Teck and Bowman, Jeff and Mahadeva, Sanjiv and Yong, Hoi Sen and Lang, Anthony E. (2021) Gut microbial ecosystem in parkinson disease: New clinicobiological insights from multi-omics. Annals of Neurology, 89 (3). pp. 546-559. ISSN 0364-5134, DOI https://doi.org/10.1002/ana.25982.
Full text not available from this repository.Abstract
Objective: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance. Methods: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry. Results; Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores. Interpretation: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021
| Item Type: | Article |
|---|---|
| Funders: | University of Malaya High Impact Research Grant [Grant No: UM.0000017/HIR.C3], University of Malaya Parkinson and Movement Disorders Research Program [Grant No: PV035-2017] |
| Uncontrolled Keywords: | Gut microbiome alterations; Parkinson disease (PD); Fecal metabolomics; Gut-brain pathophysiology |
| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
| Divisions: | Faculty of Medicine Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 21 Aug 2022 04:11 |
| Last Modified: | 21 Aug 2022 04:11 |
| URI: | http://eprints.um.edu.my/id/eprint/34663 |
Actions (login required)
 |
View Item |
