Abstract
OBJECTIVES: Polypharmacy has been linked to alterations in gut microbiota, but its effects on the oral microbiome remain underexplored. This study aimed to examine the association of polypharmacy and anticholinergic burden with oral microbiome diversity and composition. METHODS: We conducted a cross-sectional analysis using data from NHANES 2009-2012, including participants aged 55-69 years who reported at least one prescription medication. Polypharmacy was defined as the concurrent use of five or more medications. Anticholinergic burden was quantified by the Anticholinergic Cognitive Burden scale and the Anticholinergic Drug Scale. Oral microbiome profiling comprised alpha diversity, beta diversity, and taxonomic composition at multiple phylogenetic levels. Associations were analyzed via weighted multivariable linear regression, principal coordinate analysis (PCoA), and multivariate analysis of variance. RESULTS: Among 1,596 participants, 29.2% reported polypharmacy, which correlated with higher anticholinergic burden. Both polypharmacy and anticholinergic burden were inversely associated with alpha diversity across multiple measures. Taxonomic analyses showed heterogeneous associations, with Porphyromonadaceae negatively linked to both exposures. PCoA indicated significant differences in community structure by polypharmacy status (Bray-Curtis: R² = 0.35%, P < .001). CONCLUSIONS: Among middle-aged and older U.S. adults, both polypharmacy and anticholinergic burden were inversely associated with oral microbiome diversity and linked to distinct microbiome composition.