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Gut microbiota-driven metabolic reprogramming, including accumulation of toxic aromatic amino acid catabolites, is a key contributor to Parkinson's disease with REM sleep behavior disorder and idiopathic RBD.

This study found that Parkinson's disease 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. Gut microbial dysbiosis in these groups drives a functional shift away from dietary fiber fermentation toward enhanced degradation of protein, aromatic amino acids, glycine, and intestinal mucin glycans, associated with exacerbated oxidative stress, neuroinflammation, and accelerated pathological progression.

Last updated: Jul 7, 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 reduces dietary fiber fermentation
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Enhanced degradation of protein, aromatic amino acids, glycine, and intestinal mucin glycans by gut microbiota
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Accumulation of toxic aromatic amino acid catabolites in plasma
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Exacerbated oxidative stress, neuroinflammation, and accelerated pathological progression in RBD-PD and iRBD

Limitations

  • ⚠Abstract does not specify sample size or statistical effect sizes for the observed differences
  • ⚠Causal relationships between gut microbiota changes and disease progression cannot be established from observational multiomic profiling alone
  • ⚠Findings may not generalize to all PD subtypes or populations outside the study cohort

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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.