Kim Ryul, Oh Sujin, Woo Kyung Ah, Shin Cheol Min, Park Kyoung Un, Lee Jee-Young
Department of Neurology, Seoul Metropolitan Government - Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
J Neural Transm (Vienna). 2025 Jun 4. doi: 10.1007/s00702-025-02953-9.
Although systemic inflammation triggered by alterations in microbiota from various body sites has been proposed as a potential mechanism underlying Lewy body diseases (LBDs), the association between the blood microbiome and LBDs remains uncertain. This study aimed to investigate the blood microbiome profiles across the REM sleep behavior disorder (RBD)-LBD continuum and to explore their potential as biomarkers reflecting disease phenotypes and clinical severity. Blood samples were collected from 106 patients across the RBD-LBD continuum, including 41 with isolated RBD (iRBD), 45 Parkinson's disease with probable RBD, and 20 dementia with Lewy bodies with probable RBD, as well as from 94 healthy controls. All patients were evaluated with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and comprehensive neuropsychological tests. Microbiome taxonomic compositions were analyzed using 16 S rRNA metagenomic sequencing. Significant microbial shifts were observed in the RBD-LBD continuum group compared to controls, with reduced microbial alpha diversity and distinct beta diversity patterns. Specifically, the genus Stenotrophomonas was enriched, while the genera Acetobacter, Enhydrobacter, and Lactobacillus were depleted in the RBD-LBD continuum group. The combined model using these genera demonstrated high predictive accuracy for the RBD-LBD continuum, with the area under the receiver-operating-characteristic curve (AUC) of 0.970 (95% confidence interval [CI]: 0.950-0.980). This model also successfully distinguished the iRBD subgroup from controls, achieving an AUC of 0.956 (95% CI, 0.914-0.987). Alpha and beta diversity were significantly associated with MDS-UPDRS Parts I and II scores in the RBD-LBD continuum group. Our findings suggest that patients within the RBD-LBD continuum may share specific blood microbiome signatures.
尽管由身体各部位微生物群变化引发的全身炎症被认为是路易体病（LBDs）潜在的发病机制，但血液微生物群与LBDs之间的关联仍不明确。本研究旨在调查快速眼动睡眠行为障碍（RBD）-LBD连续体中的血液微生物群谱，并探索其作为反映疾病表型和临床严重程度的生物标志物的潜力。从106例RBD-LBD连续体患者中采集血样，包括41例孤立性RBD（iRBD）患者、45例可能合并RBD的帕金森病患者、20例可能合并RBD的路易体痴呆患者，以及94例健康对照者。所有患者均接受运动障碍协会统一帕金森病评定量表（MDS-UPDRS）评估和全面的神经心理学测试。使用16S rRNA宏基因组测序分析微生物群分类组成。与对照组相比，RBD-LBD连续体组观察到显著的微生物变化，微生物α多样性降低，β多样性模式明显不同。具体而言，嗜麦芽窄食单胞菌属富集，而醋杆菌属、水生杆菌属和乳杆菌属在RBD-LBD连续体组中减少。使用这些属的联合模型对RBD-LBD连续体具有较高的预测准确性，受试者工作特征曲线下面积（AUC）为0.970（95%置信区间[CI]：0.950-0.980）。该模型还成功地将iRBD亚组与对照组区分开来，AUC为0.956（95%CI，0.914-0.987）。α和β多样性与RBD-LBD连续体组的MDS-UPDRS第一部分和第二部分评分显著相关。我们的研究结果表明，RBD-LBD连续体中的患者可能具有特定的血液微生物群特征。
