New Insights into the oral microbiota and host epigenetic changes in obsessive compulsive disorder and major depressive disorder: Focus on BDNF

Obsessive-Compulsive Disorder (OCD) and Major Depressive Disorder (MDD) frequently co-occur, with depressive symptoms affecting OCD progression and vice versa. Identifying biomarkers is crucial for improving diagnosis and treatment. While the gut microbiota's role in psychiatric disorders is well-studied, this research focuses on alterations in the oral microbiota and their relationship with BDNF (Brain-Derived Neurotrophic Factor) DNA methylation in OCD and MDD patients compared to healthy controls. Our findings reveal significant changes in microbiota composition with OCD patients showing increased Actinobacteriota and Firmicutes abundances (p < 0.05; CTRL = n.24, OCD = n.29), while MDD patients exhibiting increased Actinobacteriota and Firmicutes, with reduced Bacteroidota and Proteobacteria abundances (p < 0.05; CTRL = n.24, MDD = n.20). These alterations, including potential post-streptococcal autoimmunity, highlight the microbiota's role in OCD and MDD pathophysiology. Selective changes in BDNF DNA methylation were observed in both disorders at CpG sites in exon I and IV, significantly reduced in OCD and MDD (p < 0.05; CTRL = n.24, OCD = n.29, MDD = n.20) and, following miRNome analysis, showed altered expression of BDNF-targeting microRNAs, with miR-16–5p and miR-29a-3p upregulated in OCD (p < 0.05; CTRL = n.24, OCD = n.17), and miR-29a-3p upregulated and miR-191–5p downregulated in MDD (p < 0.05; CTRL = n.24, MDD = n.16). These findings suggest disorder-specific microbiota and epigenetic profiles, positioning saliva as a non-invasive tool for biomarker identification. This research advances the understanding of microbial-epigenetic interactions in OCD and MDD, potentially guiding early diagnosis and targeted therapies.