Sex differences in oral microbiome diversity and depression

Oral microbiome diversity may be associated with depression through the oral-microbiome-brain axis; however, whether sex modifies this association is unknown. This study aimed to investigate the association between oral microbiome diversity and depression, focusing on the impact of sex differences. Data were retrieved from the National Health and Nutrition Examination Survey (NHANES) 2009-2012 cycles. The characterization of the oral microbiome was conducted through the utilization of 16S ribosomal RNA gene sequencing. The α diversity (within-sample diversity) of the oral microbiome included observed Amplicon sequence variants (ASVs), Faith's Phylogenetic Diversity, the Shannon-Weiner Index, and the Simpson Index. Patients with a Patient Health Questionnaire-9 (PHQ-9) score of ≥ 10 were included in the depressed group. The association between α diversity of the oral microbiome and depression was measured using weighted logistic regression models. In this study, 7509 individuals aged 18-69 years were included. In the overall population, reduced Faith's Phylogenetic Diversity was associated with higher risk of depression (adjusted odds ratio[aOR]=0.965;95%CI = 0.934-0.996). Among males, higher α diversity was associated with lower depression risk (observed ASVs: aOR = 0.930, 95%CI = 0.895-0.968; Faith's Phylogenetic Diversity: aOR = 0.907, 95%CI = 0.861-0.955). This trend was not observed in females for α diversity. There were some interactions between sex and α diversity (P for interaction: observed ASVs, p = 0.013; Faith's Phylogenetic Diversity, p = 0.019), except for Shannon-Weiner or Simpson Index (P for interaction > 0.05). Higher α diversity (within-sample richness and phylogenetic diversity) of the oral microbiome was associated with reduced risk of depression in adult males, but not in adult females.