ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1620449
Effects of Gut Microbiota on Cognitive Impairment in Parkinson's Disease: A Comprehensive Mendelian Randomization and Case-Control Study
Provisionally accepted
- Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
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Background Increasing evidence has suggested the potential role of the gut microbiota in Parkinson’s disease (PD). However, the relationship between the GM and Parkinson dementia disease (PDD) has remained debated, with their causal effects and underlying mechanisms yet to be fully understood. Methods Utilizing data from large-scale genome-wide association studies (GWASs) data, this study applied bidirectional and mediating Mendelian randomization (MR) to investigate the causality and underlying mechanisms between GM and PDD. In our analysis, inverse variance weighting was used as the primary method. Clinical validation was performed using metagenomic sequencing and bioinformatic analysis. The relationships between the GM and PDD were visualized using receiver operating characteristic (ROC) curves, confusion matrices, and correlation analyses. Results Our study revealed a significant causal impact of five GM genera, ten metabolites, two metabolite ratios and twenty-two immune cells on PDD. Notably, the maltose to sucrose ratio was identified as a mediator of the positive causal effect of Subdoligranulum on PDD, with a mediation ratio of 13.2%. Clinical samples confirmed the efficacy of Subdoligranulum sp. in distinguishing PDD patients from normal controls (AUC = 0.80, 95% CI: 0.674–0.924). Additionally, correlation analysis revealed a potential negative association between Subdoligranulum abundance and Mini-Mental State Examination scores (r = -0.316, p = 0.006). Finally, bioinformatic analysis suggested that Subdoligranulum may influence PDD risk through the regulation of starch and sucrose metabolism pathways. Conclusions Our study confirms the potential role of Subdoligranulum in PDD progression, potentially mediated through starch and sucrose metabolism. These findings highlight the importance of the gut‒brain axis in PDD and may provide insights into targeted interventions for PDD.
Keywords: Gut Microbiota, Parkinson dementia disease, Metabolites, Causal effect, Mendelian randomization
Received: 30 Apr 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Feng, Chang, Zhou, Xie, Deng, Chen, Liu and Zhang. 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: Weiguo Liu, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China
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