ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
This article is part of the Research TopicEpigenetic and Genetic Mechanisms Underlying Cardiovascular Diseases and Neurodevelopmental Disorders, Volume IIView all 5 articles
Sex-dependent alterations of salivary microbiome in Parkinson's disease: Associations with motor and non-motor clinical phenotypes
Provisionally accepted
JIE ZU1,2
Wei Zhang2
Li Du2
Hui Zhao2Min Xu2Ruyi Chen2Yuting Zhang2Siyan Chen2
Chuanying Xu2Liguo Dong2
Jienan Zhu2
Lishun Xiao2
Chun-Feng Liu1*- 1Second Affiliated Hospital of Soochow University, Suzhou, China
- 2The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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Background: Parkinson's disease (PD) shows considerable heterogeneity in motor and non motor features. The contribution of the salivary microbiome and its modification by sex remains unclear. Methods: In a single center cross sectional case control study, we profiled unstimulated saliva from 24 patients with Parkinson's disease and 25 age and sex matched controls using 16S rRNA sequencing. Alpha and beta diversity were evaluated, group associated taxa were identified by indicator analysis, and community structure was related to clinical measures including Unified Parkinson's Disease Rating Scale part III in off and on medication states, the Non Motor Symptoms Scale, and the Hamilton Depression Rating Scale. Results: Alpha diversity was broadly preserved, whereas richness was higher in men with Parkinson's disease than in women with PD. Beta diversity showed modest but significant separation across disease by sex groups at multiple taxonomic levels with PERMANOVA R² about 0.13 and significant P values. Women with PD displayed higher Prevotella and Veillonella with lower Akkermansia, and men with PD showed a TM7 skewed profile typified by Candidatus Saccharimonas and reduced Haemophilus. The coupling between community structure and clinical burden was strongest for motor severity and was more evident in the on medication state. Conclusion: The salivary microbiome in Parkinson's disease exhibits sex specific alterations that track clinical burden, supporting sex aware development of salivary biomarkers and microbiota focused strategies. Validation in larger longitudinal cohorts with multi omics and standardized oral and medication metadata is warranted.
Keywords: Parkinson's disease, Saliva, oral microbiome, sex differences, 16S rRNA sequencing, UPDRS
Received: 16 Oct 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 ZU, Zhang, Du, Zhao, Xu, Chen, Zhang, Chen, Xu, Dong, Zhu, Xiao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chun-Feng Liu
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