Shotgun metagenomic profiling of the gut microbiota in Parkinson's disease dementia and dementia with Lewy bodies.

BACKGROUND

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are related α-synucleinopathies that share Lewy pathology, but they differ clinically. Increasing evidence links gut microbiota (GMB) dysbiosis and microbially derived metabolites to Parkinsonian disorders yet reported associations remain heterogeneous across cohorts and the Lewy body dementia syndromes are comparatively under characterized. This study integrated clinical characterization and GMB profiling in Parkinson's disease dementia (PDD), DLB, and healthy controls (HC) to identify shared and syndrome specific features, and to relate these patterns to cognitive, neuropsychiatric, and functional outcomes.

METHODS

The present cross-sectional case-control study in Spain included 76 adults aged 60 to 85 years (HC = 38, PDD = 27, DLB = 11). Stool samples underwent shotgun metagenomic sequencing, with species-level taxonomic profiling using Kraken2. Community diversity was assessed using observed species and Chao1 richness, Shannon alpha diversity, and Bray-Curtis dissimilarity for beta diversity. LEfSe and multivariate linear modeling with MaAsLin2 were performed to identify GMB species associated with PDD and DLB and their clinical correlates.

RESULTS

PDD showed higher richness compared with HC. Shannon alpha diversity did not differ between groups. Bray-Curtis differed by separation of HC from both PDD and DLB, with no significant difference between Lewy body dementia syndromes. LEfSe identified 19 significantly differential taxa. Furthermore, several taxa showed significant multivariable associations with clinical outcomes.

CONCLUSIONS

PDD and DLB shared a broadly similar GMB alteration away from HC, with multivariable associations between several taxa and clinical outcomes. Longitudinal and functional studies are needed to clarify causality and biomarker potential.