Gut microbiota-driven metabolic reprogramming contributes to Parkinson's disease with REM sleep behavior disorder
This study found that Parkinson's disease patients with REM sleep behavior disorder (RBD-PD) exhibit distinctive metabolic disturbances, including accumulation of gut microbiota-derived toxic aromatic amino acid catabolites. These alterations were also observed in idiopathic RBD patients, representing the prodromal stage of PD. The findings suggest gut microbial dysbiosis drives a functional shift away from dietary fiber fermentation toward enhanced degradation of protein, aromatic amino acids, glycine, and intestinal mucin glycans.
Evidence Score
Study Evidence
Study 1. Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder.
observationalShao 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)
Result:
Mechanism Graph
Limitations
- ⚠Abstract does not specify sample size or statistical power
- ⚠Causal relationships cannot be established from observational multiomic profiling alone
- ⚠Findings may not generalize to all PD subtypes or non-RBD populations
Frequently Asked Questions
What is REM sleep behavior disorder (RBD) in Parkinson's disease?▼
RBD is a sleep disorder characterized by acting out dreams, and it affects 40-50% of Parkinson's disease patients. It is considered the most specific prodromal marker of PD and is associated with a more aggressive disease subtype.
How does gut microbiota contribute to Parkinson's disease with RBD?▼
The study found that gut microbial dysbiosis in RBD-PD patients shifts metabolism away from fiber fermentation toward degradation of proteins and amino acids, producing toxic aromatic amino acid catabolites that accumulate in plasma and contribute to oxidative stress and neuroinflammation.
What metabolic changes were observed in RBD-PD patients?▼
PD patients showed a shift from the tricarboxylic acid cycle toward glycolysis, dysregulated urea cycle, lipid remodeling, and activation of inflammatory pathways including PI3K-Akt, IL-17, NF-kappaB, MAPK, and TNF signaling.
Are these metabolic changes also seen in prodromal Parkinson's disease?▼
Yes, the same alterations were observed in idiopathic RBD (iRBD) patients, who represent the prodromal stage of PD, suggesting these changes occur early in disease development.
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References
- 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