Abstract
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.
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Acknowledgements
This study was funded by the National Natural Science Foundation of China (Grant Nos. 82171246, 81870998, 81901283, 82571430 and 81801254), the Key Field Research and Development Program of Guangdong Province (Grant No. 2018B030337001), the Clinical Research Plan of SHDC (Grant No. SHDC2020CR3012A), the Shanghai Rising-Star Program (Grant No. 22QA1405700), the Shanghai Sailing Program (Grant No. 22YF1440200) and the National Key Research and Development Program of China (Grant No. 2022YFE0210100). The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript.
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Y.Q. and S.X. performed the experiments, clinical analysis, and manuscript writing; X.H. and Y.L. collected the samples; Y.Z., C.M. and P.A. helped to recruit the PD patients and controls; and X.Y. performed the study design, manuscript revision and provided financial support. Q.X. designed the study, recruited the P.D. patients and controls, managed the project, provided financial support and revised the manuscript. All the authors meet the qualifications for authorship and have reviewed and approved the final version of the manuscript.
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Qian, Y., Xu, S., He, X. et al. Gut ecosystem dysfunction in parkinson’s disease: deciphering faecal metabolome-metagenome links for novel diagnostic panels. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-026-01299-7
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DOI: https://doi.org/10.1038/s41531-026-01299-7
