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Gut microbiota-driven metabolic reprogramming is a key contributor to Parkinson's disease with REM sleep behavior disorder

This study found that PD patients with RBD exhibit distinctive metabolic disturbances, including accumulation of gut microbiota-derived toxic aromatic amino acid catabolites, which were also observed in idiopathic RBD patients. The research integrated metabolomics, proteomics, and metagenomics to show that gut microbial dysbiosis drives a functional shift from fiber fermentation to enhanced protein and mucin degradation, associated with exacerbated oxidative stress and neuroinflammation.

Last updated: Aug 26, 2026•0 RCTs•📖 Read as article →

Evidence Score

Evidence Score32/100
Human RCT☆☆☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder.

observational

Shao Y, Wang J, Liu Y, Ni Y, Liu Z, Li Y, Jia Q, Li Q, Wang X, Li T, Liu M, Zhang S, Guo Y, Guo X, Wang D, Liu Y, Liu C, Cai H, Ning Y, Zhang J, Xu G, Le W · Signal transduction and targeted therapy (2026)

Participants: N/A
Duration: N/A
Intervention: Multiplatform metabolomics and proteomics analysis with metagenomic profiling of gut microbiota
Outcome: Metabolic reprogramming (shift from TCA cycle to glycolysis, dysregulated urea cycle, lipid remodeling), inflammatory pathway activation (PI3K-Akt, IL-17, NF-kappaB, MAPK, TNF), accumulation of toxic aromatic amino acid catabolites
Effect Size: N/A
Population: Parkinson's disease patients with and without RBD, and idiopathic RBD patients (prodromal stage of PD)

Result:

PubMed: 41912482DOI: 10.1038/s41392-026-02613-8

Mechanism Graph

Gut microbial dysbiosis in RBD-PD and iRBD reduces dietary fiber fermentation
↓
Dysbiosis enhances degradation of protein, aromatic amino acids, glycine, and intestinal mucin glycans
↓
This leads to accumulation of toxic aromatic amino acid catabolites
↓
Result: Exacerbated oxidative stress, neuroinflammation, and accelerated pathological progression in PD

Limitations

  • ⚠Abstract does not specify sample size or provide statistical effect sizes for key findings
  • ⚠Causal inference is limited as the study is observational and cross-sectional in nature
  • ⚠The study does not report whether confounding factors (e.g., medication, diet) were controlled for

Frequently Asked Questions

What is REM sleep behavior disorder (RBD) and how common is it in Parkinson's disease?▼

RBD is a sleep disorder where people physically act out vivid dreams. It affects 40-50% of Parkinson's disease patients and is considered the most specific prodromal marker of PD.

What metabolic changes were found in PD patients with RBD?▼

PD patients with RBD showed a shift from TCA cycle to glycolysis, dysregulated urea cycle, lipid remodeling, and accumulation of gut microbiota-derived toxic aromatic amino acid catabolites.

How does gut microbiota contribute to Parkinson's disease with RBD?▼

Gut microbial dysbiosis drives a functional shift away from fiber fermentation toward enhanced degradation of protein, aromatic amino acids, and intestinal mucin glycans, leading to increased oxidative stress and neuroinflammation.

Were these metabolic changes also seen in people with idiopathic RBD?▼

Yes, the same metabolic disturbances, including accumulation of toxic aromatic amino acid catabolites, were observed in idiopathic RBD patients, who represent the prodromal stage of Parkinson's disease.

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References

  1. 1.Shao Y, Wang J, Liu Y, Ni Y, Liu Z, Li Y, Jia Q, Li Q, Wang X, Li T, Liu M, Zhang S, Guo Y, Guo X, Wang D, Liu Y, Liu C, Cai H, Ning Y, Zhang J, Xu G, Le W. "Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder.." Signal transduction and targeted therapy, 2026. PMID: 41912482 DOI: 10.1038/s41392-026-02613-8
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.