Adolescent depression and gut microbiota dysbiosis: characteristics, mechanisms, and microbiota-targeted therapeutics

Major depressive disorder (MDD) is one of the most prevalent mental disorders, yet its pathogenesis remains incompletely understood. Accumulating evidence indicates that MDD is closely associated with gut microbiota dysbiosis, with bidirectional communication along the microbiota-gut-brain axis playing a pivotal role in disease development. The gut microbiota and its metabolites exert dual influences on MDD, contributing to its pathophysiology while also offering promising therapeutic targets. In recent years, the prevalence of depression, especially in adolescents, has shown a sharp upward trend, increasing the risk of suicide in this population. However, few studies have systematically reviewed the link between gut dysbiosis and MDD in adolescents. This review summarizes current evidence on structural and functional alterations of the gut microbiota in adolescent MDD and explores the underlying mechanisms mediated by the microbiota-gut-brain axis. Furthermore, we also discuss the therapeutic potential of microbiota-targeted interventions, including dietary modification, probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Future research should aim to characterize specific microbial alterations in adolescent MDD and clarify the mechanisms underlying gut-brain interactions, thereby advancing the clinical translation of microbiota-targeted therapeutics for adolescent depression.