Blood microbiome signatures in the REM sleep behavior disorder-Lewy body disease continuum.

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.