Integration of the serum metabolome and gut microbiome underscores the importance of altered lipid metabolism and potential immune modulation in Parkinson's Disease

Introduction: Single-omics studies have deepened our understanding of disease-related molecular processes, though integrated approaches are needed to uncover cross-system interactions. We previously reported changes in the serum metabolome and gut microbiome in Parkinson's disease (PD). To build on these findings, we conducted a multi-omics integration analysis to examine the interplay between the gut microbiome and human metabolism in PD. Methods: In a community-based study of 113 PD patients from rural California, microbiome profiles were obtained via 16S rRNA gene sequencing of fecal samples. Serum metabolomic profiles were generated using untargeted high-resolution LC-MS. Residual matrices of metabolomics data were extracted after adjusting for age, sex, racial minority status, and study wave. We identified PD-associated bacterial genera and summarized their abundance using principal component analysis. Using this summary score as the dependent variable, we performed partial least squares (PLS) regression to identify serum metabolites associated with the PD-related gut microbiome. Pathway enrichment analysis was then conducted on selected metabolite features from the PLS model. Results: < 0.1). Enrichment analysis revealed perturbed pathways in lipid metabolism, including fatty acid activation and metabolism, linoleate metabolism, and glycerophospholipid metabolism, as well as carbohydrate metabolism such as hexose phosphorylation and starch/sucrose metabolism. Conclusion: Our multi-omics integration analysis revealed that PD-associated gut microbiota are involved in host lipid metabolism, immune-related pathways, and potentially vitamin B-mediated regulation of kynurenine pathway metabolism, providing insights into potential microbiome-metabolome interactions in PD pathophysiology.