Gut ecosystem dysfunction in parkinson’s disease: deciphering faecal metabolome-metagenome links for novel diagnostic panels

Gut ecosystem dysfunction is implicated in Parkinson's disease (PD), but integrative faecal metabolome-metagenome links are undefined. We explored these interactions in Chinese PD patients to develop diagnostic panels. Targeted faecal metabolomics (LC‒MS/MS) was performed on 132 PD and 113 healthy controls (HCs) and shotgun metagenomics was integrated for 39 PD/HC pairs. We identified 33 significantly altered faecal metabolites in PD (FDR-P < 0.05). A novel 12-metabolite panel could distinguish PD from HCs. Multi-omic integration revealed gut ecosystem dysfunction manifests via co-disruptions in microbial genes (e.g., amino acid metabolism genes) and metabolites. Critically, a combinatorial diagnostic panel integrating faecal metabolites and microbial gene markers achieved exceptional PD detection (AUC = 0.961, 95% CI = 0.923-0.998). This study deciphers metabolome-metagenome links driving gut dysfunction in PD, identifying amino acid metabolism as a core perturbed pathway. The novel diagnostic panels provide mechanistic insights and clinical tools for PD precision diagnosis.