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This study aimed to investigate the blood microbiome profiles across the REM sleep behavior disorder (RBD)\u2013LBD continuum and to explore their potential as biomarkers reflecting disease phenotypes and clinical severity. Blood samples were collected from 106 patients across the RBD\u2013LBD continuum, including 41 with isolated RBD (iRBD), 45 Parkinson\u2019s 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\u2013Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) and comprehensive neuropsychological tests. Microbiome taxonomic compositions were analyzed using 16\u00a0S rRNA metagenomic sequencing. Significant microbial shifts were observed in the RBD\u2013LBD continuum group compared to controls, with reduced microbial alpha diversity and distinct beta diversity patterns. Specifically, the genus <jats:italic>Stenotrophomona<\/jats:italic>s was enriched, while the genera <jats:italic>Acetobacter<\/jats:italic>, <jats:italic>Enhydrobacter<\/jats:italic>, and <jats:italic>Lactobacillus<\/jats:italic> were depleted in the RBD\u2013LBD continuum group. The combined model using these genera demonstrated high predictive accuracy for the RBD\u2013LBD continuum, with the area under the receiver-operating-characteristic curve (AUC) of 0.970 (95% confidence interval [CI]: 0.950\u20130.980). This model also successfully distinguished the iRBD subgroup from controls, achieving an AUC of 0.956 (95% CI, 0.914\u20130.987). Alpha and beta diversity were significantly associated with MDS-UPDRS Parts I and II scores in the RBD\u2013LBD continuum group. Our findings suggest that patients within the RBD-LBD continuum may share specific blood microbiome signatures.<\/jats:p>","DOI":"10.1007\/s00702-025-02953-9","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T06:22:36Z","timestamp":1749018156000},"page":"1143-1154","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Blood microbiome signatures in the REM sleep behavior disorder\u2013Lewy body disease continuum"],"prefix":"10.1007","volume":"132","author":[{"given":"Ryul","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujin","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung Ah","family":"Woo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheol Min","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoung Un","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9120-2075","authenticated-orcid":false,"given":"Jee-Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"issue":"1","key":"2953_CR1","doi-asserted-by":"publisher","first-page":"e54461","DOI":"10.1371\/journal.pone.0054461","volume":"8","author":"J Amar","year":"2013","unstructured":"Amar J, Lange C, Payros G, Garret C, Chabo C, Lantieri O, Courtney M, Marre M, Charles MA, Balkau B, Burcelin R (2013) Blood microbiota dysbiosis is associated with the onset of cardiovascular events in a large general population: the D.E.S.I.R. 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