Associations of oral microbiome diversity with prevalent cancer: a population-based cross-sectional study

Oral microbiome interacts with other organ systems and significantly impacts human health. However, analysis of its role in cancer remains scarce. This study aims to explore the relationship between oral microbiome diversity and prevalent cancer. We analyzed 7727 adults from the 2009-2012 National Health and Nutrition Examination Survey. The linear and non-linear associations between α-diversity and cancer were evaluated using multivariable logistic regression analysis and restricted cubic spline functions. Principal coordinates analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) were also used to evaluate differences in β-diversity by cancer status. We found a negative association between oral microbiome α-diversity and the odds of cancer. After adjusting for all confounding covariates, participants in the highest tertile of diversity had 42-46% lower odds of cancer compared to those in the lowest tertile (OTU richness OR = 0.54, 95% CI 0.33-0.87, Ptrend = 0.007; Faith's phylogenetic diversity OR = 0.58, 95% CI 0.35-0.94, Ptrend = 0.012). Exploratory β-diversity analyses showed statistically significant but limited differences in overall microbial community composition according to cancer status. Subgroup analyses suggested a potential effect modification by age, with participants younger than 65 years showing sensitivity to modest elevation in microbiome diversity. Additionally, certain characteristics were associated with lower oral microbiome α-diversity, including age 40 onwards, female sex, lower income, and antibiotics use. Our findings reveal that higher oral microbiome diversity is associated with lower odds of having cancer, which suggests that microbiota profiles may have potential utility in cancer-related risk stratification.