LC‐MS based urine metabolomic profiling indicate altered gut microbiome and host lipid metabolites in Parkinson’s disease

Evidence indicates that host and gut microbial metabolism are dysregulated prior to the onset of motor symptoms, in the prodromal phase of Parkinson's disease (PD). There is currently no definitive test for the diagnosis of Parkinson's disease; this represents an urgent, unmet medical need to enable the effectiveness of current and future therapeutic interventions for PD. The aim of this study was to understand changes in host and microbial metabolism in PD patient biofluids which could reflect a transition from the healthy to diseased state. We performed a comprehensive untargeted metabolomics analysis of urinary lipid metabolites together with altered metabolites associated with the gut microbiota. A total of 64 urine samples consisting of 31 from age matched healthy controls and 33 from PD patients were used in this study. Samples were deproteinized and analysed by reverse phase (RP)/UPLC-MS/MS methods with positive and negative ion mode electrospray ionization (ESI) and HILIC/UPLC-MS/MS with negative ion mode ESI. 14 lipid metabolites were significantly altered in PD patients. Five metabolites were associated with bile acid metabolism and nine were from the cholesterol pathway. Changes in secondary bile acid metabolism, particularly secondary bile acids indicative of microbial metabolism changes, were evident in PD patients, with 11 altered metabolites associated with the gut microbiota being significantly altered. Interestingly, several lipid metabolites that were altered in PD patients correlated with specific gut microbiome metabolites. Our results provide new insights into altered lipid metabolism and gut dysbiosis in PD, however, confirmation in a larger cohort would be needed.