Association between oral microbiome and depression: A population-based study

Objective: Depression is a global mental health issue, particularly affecting adolescents and young adults. While the role of gut microbiota in depression has been extensively studied, the influence of the oral microbiome remains underexplored. Recent studies suggest that the oral microbiome may affect systemic and brain health through the oral-brain axis. This study aimed to investigate the relationship between oral microbiome diversity and depression using data from 6212 participants in the National Health and Nutrition Examination Survey (NHANES) 2009-2012. Methods: Oral microbiome diversity was assessed through oral rinse samples using 16S rRNA sequencing, focusing on alpha-diversity metrics (observed ASVs and Faith's phylogenetic diversity) and beta-diversity measures. Depressive symptoms were evaluated with the Patient Health Questionnaire (PHQ-9). Weighted logistic regression models were employed to assess associations between alpha-diversity and depression, while linear regression was used to examine the relationship between alpha-diversity and PHQ-9 scores. beta-diversity differences were analyzed via permutational analysis of variance (PERMANOVA). Results: 10.03% of the participants were diagnosed with depression. Higher alpha-diversity in the oral microbiome was negatively correlated with depression: observed ASVs (OR: 0.713 [CI: 0.508-0.999], P = 0.050) and Faith's phylogenetic diversity (OR: 0.584 [CI: 0.367-0.931], P = 0.025). Linear regression indicated that greater alpha-diversity was associated with lower PHQ-9 scores, reflecting fewer depressive symptoms. Furthermore, beta-diversity analysis revealed significant differences in the microbiome composition between depressed and non-depressed individuals. Conclusion: Reduced oral microbiome diversity is associated with an increased risk and severity of depression. The study underscores the importance of exploring the oral-brain axis and highlights the need for further research into the mechanisms and therapeutic strategies targeting this relationship.