Feng Yukun, Chang Qi, Zhou Hao, Zhang Wei, Xie Ling, Deng Xueyang, Chen Tao, Liu Weiguo
Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.
Department of Neurology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Front Microbiol. 2025 Aug 25;16:1620449. doi: 10.3389/fmicb.2025.1620449. eCollection 2025.
Increasing evidence suggests a potential role of the gut microbiota in Parkinson's disease (PD). However, the relationship between the gut microbiome (GM) and PD dementia (PDD) remains debated, with their causal effects and underlying mechanisms not yet fully understood.
Utilizing data from large-scale genome-wide association studies (GWASs), this study applied bidirectional and mediating Mendelian randomization (MR) to investigate the causal relationship and underlying mechanisms between the GM and PDD. In our analysis, inverse-variance weighting (IVW) 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.
Our study revealed a significant causal impact of five GM genera, 10 metabolites, two metabolite ratios, and 22 immune cells on PDD. Notably, the maltose to sucrose ratio was identified as a mediator of the positive causal effect of on PDD, with a mediation value of 13.2%. The clinical samples confirmed the efficacy of sp. in distinguishing patients with PDD from normal controls (area under the curve (AUC) = 0.80, 95% CI: 0.674-0.924). In addition, correlation analysis revealed a potential negative association between abundance and the Mini-Mental State Examination (MMSE) scores (r = -0.316, = 0.006). Finally, bioinformatic analysis suggested that may influence PDD risk through the regulation of starch and sucrose metabolism pathways.
Our study confirms the potential role of 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.
越来越多的证据表明肠道微生物群在帕金森病（PD）中具有潜在作用。然而，肠道微生物组（GM）与PD痴呆（PDD）之间的关系仍存在争议，它们的因果效应和潜在机制尚未完全明确。
本研究利用大规模全基因组关联研究（GWAS）的数据，应用双向和中介孟德尔随机化（MR）来研究GM与PDD之间的因果关系和潜在机制。在我们的分析中，采用逆方差加权（IVW）作为主要方法。使用宏基因组测序和生物信息学分析进行临床验证。GM与PDD之间的关系通过受试者工作特征（ROC）曲线、混淆矩阵和相关性分析进行可视化。
我们的研究揭示了5个GM属、10种代谢物、2种代谢物比率和22种免疫细胞对PDD有显著的因果影响。值得注意的是，麦芽糖与蔗糖的比率被确定为[具体物质]对PDD产生正向因果效应的中介，中介值为13.2%。临床样本证实了[具体菌种]在区分PDD患者与正常对照方面的有效性（曲线下面积（AUC）=0.80，95%CI：0.674 - 0.924）。此外，相关性分析显示[具体菌种]丰度与简易简易简易精神状态检查表（MMSE）评分之间存在潜在的负相关（r = -0.316，P = 0.006）。最后，生物信息学分析表明[具体菌种]可能通过调节淀粉和蔗糖代谢途径影响PDD风险。
我们的研究证实了[具体菌种]在PDD进展中的潜在作用，可能通过淀粉和蔗糖代谢介导。这些发现突出了肠 - 脑轴在PDD中的重要性，并可能为PDD的靶向干预提供见解。
