Integrated Analyses of Microbiome and Longitudinal Metabolome Data Reveal Microbial-Host Interactions on Sulfur Metabolism in Parkinson's Disease

Abstract

Parkinson’s disease (PD) exhibits systemic effects on human metabolism with emerging roles for the gut microbiome. Here, we integrate longitudinal metabolome data from 30 drug-naive, de-novo PD patients and 30 matched controls with constraint-based modeling of gut microbial communities derived from an independent, drug-naive PD cohort. Our key results are i) metabolites associated with the interconversion of methionine and cysteine via cystathionine differed strongly in their longitudinal trajectory between PD patients and controls, ii) dopaminergic medication showed strong lipidomic signatures, iii) histidine and taurine-conjugated bile acids correlated with the severity of motor symptoms, with low baseline histidine levels being predictive for faster disease progression, and iv) computational modeling predicted changes in microbial sulfur metabolism, driven by A. muciniphila and B. wadsworthia, and consistent with the changed metabolome. In conclusion, the integration of metabolomic and metagenomic data revealed substantial PD-specific patterns in microbial-host sulfur metabolism that may contribute to PD’s severity.