Beyond the Gut: Integrating Oral Microbiota into the Microbiota-Brain Axis in Depression.

Depression, a major contributor to years lived with disability (YLD), affects nearly 300 million people worldwide. In the aftermath of the COVID-19 pandemic, cases of major depressive disorder (MDD) or clinical depression have risen by 28% particularly among women and young adults. Characterized by persistent low mood, cognitive impairment, suicidal ideation, sleep disturbances, appetite changes, and fatigue, depression continues to impose a profound public health burden, compounded by the limited efficacy of current treatments and the lack of reliable diagnostic or predictive biomarkers. While the gut microbiota has been extensively implicated in depression's pathophysiology, emerging evidence indicates that the oral microbiome which ranks second only to the gut in microbial diversity also plays a significant role in neuropsychiatric health. Oral microbial dysbiosis may contribute to depression through immune, inflammatory, and neuroactive pathways, positioning the oral microbiome as both a potential non-invasive biomarker and a novel therapeutic target. Incorporating oral microbial profiling into clinical research could not only refine our understanding of depression's underlying mechanisms but also facilitate the development of microbiome-based strategies in precision psychiatry. This growing recognition highlights the importance of expanding research beyond the gut-brain axis to encompass the oral-brain axis as an integral component in the quest for effective diagnostics and interventions.