Integrative multi-omics analysis reveals host-microbiome metabolic alterations and candidate biomarkers in...

Alterations in the gut microbiome have been increasingly implicated in Parkinson's disease (PD), but the associated metabolic changes remain incompletely understood. Here, we applied an integrative multi-omics approach combining shotgun metagenomic sequencing and untargeted LC-MS-based plasma metabolomics to investigate host-microbiome alterations in PD. Fecal and plasma samples were collected from 30 PD patients and 30 healthy spouse controls. Significant differences in microbial diversity and taxonomic composition were observed between the two groups. Taxonomic profiling revealed marked gut microbial dysbiosis in PD, including altered abundances of Phocea massiliensis, Bacteroides sp900766005, and Alistipes_A indistinctus. Metabolomic analysis identified 86 significantly altered plasma metabolites, including glycerophospholipids, indoleacetic acid, and kynurenic acid. Integrative pathway analysis suggested links between microbial functional alterations and host metabolic changes. Machine-learning analyses identified three biomarker panels that distinguished PD patients from controls in validation datasets, with the highest area under the curve (AUC) reaching 0.92. In silico molecular docking further suggested potential interactions between several metabolite biomarkers and alpha-2-macroglobulin (A2M) or the human B^act spliceosome. Overall, these findings provide an integrative view of host-microbiome metabolic alterations associated with PD and highlight candidate biomarkers and exploratory host-metabolite associations for further investigation.