Related Experiment Video
Updated: Aug 6, 2026
04:33
Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder
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
Summary
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.
Related Concept Videos
01:22Gut-Brain Axis
The gut–brain axis is a bidirectional communication system that connects the gastrointestinal tract and the brain. This interaction is mediated through multiple pathways, including the vagus nerve, hormonal signals, immune responses, and chemical messengers produced by gut microbes.Microbial Contributions to Brain FunctionGut microbiota contributes significantly to brain function by producing neuroactive compounds. These include neuroactive compounds that influence neurotransmitters such as...
01:15REM Sleep Behavior Disorder
REM Sleep Behavior Disorder (RBD) is a sleep disorder characterized by the absence of muscle paralysis that normally occurs during the REM phase of sleep. This absence allows individuals to physically act out their dreams, which are often vivid and disturbing. Common behaviors exhibited during episodes include kicking, punching, and yelling. These actions can be dangerous, potentially leading to injuries for the person with RBD or their bed partner.
RBD is significantly associated with...
RBD is significantly associated with...
01:18Depression: Overview
Depression is a prevalent mental illness marked by persistent sadness and lack of interest in previously enjoyable activities. It can take several forms, including major depression, persistent depressive disorder, and bipolar I and II disorders. Symptoms range from emotional changes like chronic worry to physical changes like sleep disturbances and suicidal thoughts. From a neurobiological perspective, depression is believed to be triggered by abnormalities in the brain's prefrontal cortex,...
01:18Dysbiosis of the Gut Microbiota
The human gut microbiome includes a diverse array of microbial species, including beneficial commensals and opportunistic pathogens, which interact to support host health. These microbes contribute to essential functions such as nutrient metabolism, immune system modulation, and maintenance of intestinal barrier integrity. However, disruptions to this equilibrium—referred to as dysbiosis—can have widespread physiological consequences.Dysbiosis is often characterized by reduced microbial...
01:21Microbiota Modulation by Antibiotics
Antibiotics have revolutionized modern medicine by saving countless lives from bacterial infections. However, their widespread use has inadvertently harmed the delicate balance of the human gut microbiota. The gut microbiota, a complex community of bacteria, archaea, viruses, and fungi, plays a vital role in regulating metabolism, immune responses, and maintaining intestinal health. Antibiotics, especially broad-spectrum types, disrupt this ecosystem by eradicating both harmful and beneficial...
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.