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Published on: April 26, 2024

Gut Microbiome in Depression with and without REM Sleep Behavior Disorder

Yuhua Yang1,2, Ningning Li1,2, Li Zhou1,2,3

  • 1Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.

Molecular Psychiatry
|July 23, 2026
PubMed

Insights

Major depressive disorder with REM sleep behavior disorder (MDD+RBD) may be a distinct subtype indicating neurodegeneration risk. Gut microbiome analysis revealed unique microbial signatures in MDD+RBD, differentiating it from other groups.

Area of Science:

  • Neuropsychiatry
  • Microbiome Research
  • Neurodegenerative Diseases

Background:

  • Major depressive disorder (MDD) is a risk factor for neurodegeneration, but its heterogeneity complicates subtype identification.
  • REM sleep behavior disorder (RBD) is a prodrome of α-synucleinopathy, and its comorbidity with MDD warrants investigation into neurodegenerative risk.
  • The gut-brain axis plays a crucial role in neuropsychiatric disorders, suggesting microbial signatures may differentiate MDD subtypes.

Purpose of the Study:

  • To delineate the microbial signatures associated with comorbid Major Depressive Disorder and REM Sleep Behavior Disorder (MDD+RBD).
  • To investigate whether MDD+RBD represents a distinct subtype with higher neurodegenerative risk compared to MDD alone.
  • To explore the potential of the gut microbiome for risk stratification in psychiatric populations.

Main Methods:

  • A four-group case-control study (N=420) including healthy controls (HC), MDD-only, MDD+RBD, and idiopathic RBD (iRBD).
  • Clinical evaluations and fecal metagenomic sequencing were performed on all participants.
  • A Random Forest machine-learning model was developed to distinguish MDD+RBD from MDD-only, validated on an independent dataset.

Main Results:

  • MDD+RBD patients exhibited prodromal neurodegenerative features, including olfactory deficits and subtle motor signs, resembling iRBD.
  • Microbial composition in MDD+RBD differed significantly from HC and MDD-only, showing an iRBD-like dysbiosis (e.g., enriched Akkermansia muciniphila, depleted Faecalibacterium prausnitzii).
  • The Random Forest model accurately distinguished MDD+RBD from MDD-only with an AUC of 0.79 in the validation dataset, indicating distinct microbial profiles.

Conclusions:

  • MDD+RBD may represent a biologically distinct subtype of depression associated with increased neurodegenerative risk.
  • Gut microbiome alterations in MDD+RBD patients mirror those in iRBD, suggesting shared pathophysiological pathways.
  • Microbiome analysis offers a promising avenue for identifying individuals at higher risk for neurodegeneration within psychiatric cohorts.

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