Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease

Sinclair, Eleanor; Trivedi, Drupad K.; Sarkar, Depanjan; Walton-Doyle, Caitlin; Milne, Joy; Kunath, Tilo; Rijs, Anouk M.; Bie, Rob M.A. de; Goodacre, Royston; Silverdale, Monty; Barran, Perdita E.

doi:10.1038/s41467-021-21669-4

Cited by 103 publications

(102 citation statements)

References 60 publications

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“…Using mummichog approach, we have shown in this study that the identified serum metabolome differences in PD have functional significance on over 20 pathways, including carnitine shuttle, vitamin E metabolism, glycerophospholipids, sphingolipids, fatty acids, and aminoacyl-tRNA biosynthesis. In a separate study, we have demonstrated that carnitine shuttle, sphingolipids, and fatty acids pathways change in Parkinson’s sebum - these are within the 20 pathways enlisted above detected in serum in this study 14 . Energy metabolism is highly regulated by facilitation of long chain fatty acid β-oxidation.…”

Section: Discussionsupporting

confidence: 65%

“…Lactobacillus (increased in PD) is negatively correlated with a furanoic fatty acid, which is associated with cell signalling, lipid peroxidation, lipid metabolism, and lipid transport metabolism, with dietary, human, and/or bacterial origin. Half of the metabolites from the fatty acyl class were found to be overrepresented in PD in the selected PD sebum data from Sinclair et al (2021) 14 .…”

Section: Correlations Between Bacterial Taxa and Metabolites Featuresmentioning

confidence: 97%

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Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Pereira

Silverman

et al. 2021

Preprint

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We aimed to investigate the link between serum metabolites, gut bacterial community composition, and clinical variables in Parkinsons disease (PD) and healthy control subjects (HC). 139 metabolite features were found to be differentially abundant between the PD and Control groups. No associations were found between metabolite features and within-PD clinical variables. The results suggest alterations in serum metabolite profiles in PD, and the results of correlation analysis between metabolite features and microbiota suggest that several bacterial taxa are associated with altered lipid and energy metabolism in PD.

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Section: Discussionsupporting

confidence: 65%

Section: Correlations Between Bacterial Taxa and Metabolites Featuresmentioning

confidence: 97%

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Pereira

Silverman

et al. 2021

Preprint

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“…We add to the body of evidence with this in silico investigation involving zebrafish telomerase mutants, suggesting that the source of retinoid depletion in AD and PD is ageing-related. Interestingly, regarding our finding for skin ageing in zebrafish, lipid biomarkers have been proposed in a recent skin sebum metabolomics study in PD patients (Sinclair et al, 2021). This could be interpreted as co-ageing in brain and skin tissues, possibly allowing for cheap, non-invasive prognostic testing for PD.…”

Section: Discussionmentioning

confidence: 75%

Systems analysis reveals ageing-related perturbations in retinoids and sex hormones in Alzheimer’s and Parkinson’s diseases

Lam

Hartmann

Benfeitas

et al. 2021

Preprint

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Neurodegenerative diseases (NDDs), including Alzheimer's (AD) and Parkinson's diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analyse transcriptomic data from AD and PD patients, and stratify these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identify retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrate that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.

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“…Current research on biological markers of PD focuses on neuroimaging combined with biochemical markers ( Sinclair et al, 2021 ). Although a perfect biomarker has not yet been found, great progress has been made in the search for biomolecules and image types.…”

Section: Discussionmentioning

confidence: 99%

Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson’s Disease

Zhong

Chen

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is a chronic and progressive degenerative disease of the central nervous system. Degenerative neuropathy can occur in patients with PD even before typical clinical symptoms appear in the preclinical stage. Therefore, if the early diagnosis of degenerative diseases can be timely and the correlation with the disease progression can be explored, the disease progression will be slowed down and the quality of life of patients will be improved. In this study, the circRNA microarray was employed to screen the dysregulated circRNA in plasma samples of PD. Four circRNAs (circ_0085869, circ_0004381, circ_0017204, and circ_0090668) were obtained with increased levels in PD patients by cross comparison and preliminary verification in PD comparing with healthy controls. Further validation found the circRNA panel was consistent with the training set. The ROC curve also revealed a high diagnostic ability of circ_0004381 and circ_0017204 in predicting the early stage of PD from healthy controls. circ_0085869, circ_0004381, circ_0017204, and circ_0090668 also presented a high ability to distinguish the late stage of PD from early stage. In conclusion, circulating circRNA panel might be a potential fingerprint for predicting the early diagnosis of PD and may act as a biomarker for disease progression.

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Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease

Cited by 103 publications

References 60 publications

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Multiomics implicate gut microbiota in altered lipid and energy metabolism in Parkinson’s disease

Systems analysis reveals ageing-related perturbations in retinoids and sex hormones in Alzheimer’s and Parkinson’s diseases

Circulating CircRNAs Panel Acts as a Biomarker for the Early Diagnosis and Severity of Parkinson’s Disease

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