Habitual Diet, Gut Microbiome Dysbiosis, and α-Synucleinopathy Conversion in Isolated Rapid Eye Movement (REM) Sleep Behavior Disorder.

BACKGROUND

Accumulating evidence indicates that habitual diet, including plant-based dietary patterns, is associated with neurodegenerative α-synucleinopathy risk. However, the role of diet and its correlation with the gut microbiome in prodromal α-synucleinopathy, specifically among patients with isolated rapid eye movement (REM) sleep behavior disorder (iRBD), remains unclear.

OBJECTIVE

To evaluate dietary patterns, their interplay with gut microbial dysbiosis, and longitudinal effects on neurodegenerative progression in iRBD patients.

METHODS

We recruited 287 iRBD patients and 208 age- and sex-matched controls. Plant-based diet indices (PDIs) were derived from food frequency questionnaires. Shotgun metagenomic sequencing was performed in 456 subjects for diet-microbiome analyses. After a median follow-up of 4.2 years, 45 (15.7%) iRBD patients converted to α-synucleinopathies. Cox proportional hazards models assessed the associations between diet and neurodegenerative outcomes.

RESULTS

We found that iRBD patients exhibited lower healthful PDIs (adjusted odds ratio [aOR] 95% confidence interval [95% CI]: 0.48 [0.29-0.80], P = 0.005) but higher consumption of unhealthful plant-based foods (refined grains, sweets, and sweeteners). Diet-microbiome interaction analysis identified dietary associations for 84.3% of iRBD-related gut microbes, including co-occurrence between healthful PDI and Clostridium sp. AF20-17LB. Longitudinally, four dietary factors and five iRBD-related microbes were associated with neurodegenerative outcomes; specifically, higher coffee consumption was linked to a lower risk of progression to α-synucleinopathy (aHR [95% CI]: 0.30 [0.11-0.78], P = 0.01). Furthermore, mediation analyses indicated that the iRBD-enriched species Ruthenibacterium lactatiformans mediated the association between unhealthful PDI and dementia-first conversion.

CONCLUSIONS

Habitual diet in iRBD is associated with gut microbiome dysbiosis and predicts neurodegenerative progression. These findings highlight diet-microbiome interactions as modifiable targets for intervention in prodromal α-synucleinopathy. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.