Objective: To investigate whether disease-related microbial dysbiosis modifies the relationship between dietary intake and gut microbiome composition and function in Parkinson’s disease (PD) and idiopathic REM sleep behaviour disorder (iRBD).

Background: Diet is a key environmental factor shaping the gut microbiome. Alterations in microbial composition have been reported in PD and in iRBD, a prodromal stage of synucleinopathy. However, it remains unclear whether disease-associated dysbiosis alters how dietary factors interact with the gut microbiome in these populations.

Method: We recruited patients with PD (n=87), iRBD (n=15), and healthy controls (n=45). PD participants were stratified by premotor RBD into PD-RBD+(n=44) and PD-RBD−(n=43). Dietary intake was assessed using a validated food frequency questionnaire, enabling quantification of total nutrient intake and nutrients derived from ultra-processed foods. Stool samples underwent shotgun metagenomic sequencing. Associations between dietary components, taxonomic composition, and functional pathways were analyzed across groups.

Results: Total dietary intake did not significantly differ among PD, iRBD, and controls, likely reflecting similar living environments and dietary habits. Despite this similarity, diet–microbiome association patterns differed by disease status. The PD-RBD+ subgroup showed distinct interaction patterns compared with controls, particularly involving lipid intake. Higher lipid consumption, especially from ultra-processed foods, was associated with reduced microbial alpha diversity and shifts in microbial composition in PD-RBD+. Taxonomic analyses revealed group-specific associations: Leuconostoc and Latilactobacillus showed inverse relationships with sugar and fiber intake in PD-RBD+, whereas Veillonella was negatively associated with lipid intake in controls and PD-RBD−. Functional pathway analysis showed that dietary fiber intake correlated with rhamnose degradation and butyrate synthesis pathways in healthy individuals, but these associations were attenuated in PD groups.

Conclusion: Disease-related microbial dysbiosis appears to reshape diet–microbiome interactions in PD and its prodromal stage. Identical dietary exposures may therefore produce different microbial responses depending on disease status, suggesting that dietary modification alone may have limited ability to restore microbiome balance in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/altered-diet-microbiome-associations-in-parkinsons-disease-and-prodromal-rem-sleep-behavior-disorder/