ArticleMolecular psychiatry2026
Gut Microbiome in Depression with and without REM Sleep Behavior Disorder.
Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
23 authors.
Funding
Abstract
Major depressive disorder (MDD) is a risk factor for neurodegeneration, yet its heterogeneity makes identifying at-risk subtype challenging. Notably, MDD frequently co-occurs with REM sleep behavior disorder (RBD), a specific prodrome of α-synucleinopathy. It remains unclear whether comorbid MDD + RBD reflects a benign antidepressant effect, or higher neurodegenerative risk. Given growing recognition of gut-brain axis in neuropsychiatry, we aimed to delineate microbial signatures of MDD + RBD. We employed a four-group case-control design (N = 420) comprising 124 healthy controls (HC); 80 MDD without RBD features (MDD-only); 82 MDD + RBD; and 134 iRBD without psychiatric disease. All participants underwent clinical evaluation and provided fecal samples for metagenomic sequencing. Random Forest model was used to distinguish MDD + RBD, and further assessed in a validation dataset of 65 participants with MDD + RBD (n = 31) and MDD-only (n = 34). MDD + RBD exhibited prodromal neurodegenerative features, including elevated total likelihood ratio of prodromal Parkinson's Disease, olfactory deficits, and subtle motor signs. The microbial composition in MDD + RBD differed from HC and MDD-only, while resembling iRBD. Taxonomically, MDD + RBD exhibited an iRBD-like dysbiosis (e.g., enriched Akkermansia muciniphila, Ruthenibacterium lactatiformans; depleted Faecalibacterium prausnitzii), alongside depression-associated shifts (e.g., Streptococcus parasanguinis and Actinomyces oris). Functionally, MDD + RBD showed attenuated capacity of B‑vitamin biosynthesis and polysaccharides degradation, mirroring iRBD. The Random Forest machine-learning model distinguished MDD + RBD in older adults from MDD-only with an AUC of 0.73 in cross-validation and 0.79 in the validation dataset. MDD + RBD may represent a biologically distinct depression subtype associated with potential neurodegenerative risk. Gut microbiome provides a candidate approach for potential risk stratification in psychiatric populations.
Identifiers
42493609What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.