Abstract
Emerging evidence has highlighted that altered gut microbiota are associated with the onset and progression of depression via regulating the gut-brain axis. However, existing research has predominantly focused on children and adults, frequently neglecting adolescent depression. Given the rising prevalence and substantial impact of adolescent depression on functional impairment and suicidality, it is essential to focus more on this age group. In this study, we examined the fecal microbiota and inflammatory profiles of 99 depressed adolescents and 106 age-matched healthy controls using Illumina NovaSeq sequencing and multiplex immunoassays, respectively. Our findings revealed lower bacterial α-diversity and richness, alongside altered β-diversity in adolescents with depression. Gut dysbiosis associated with adolescent depression was characterized by increased pro-inflammatory genera such as Streptococcus and decreased anti-inflammatory genera like Faecalibacterium. These differential genera may serve as potential non-invasive biomarkers for adolescent depression, either individually or in combination. We also observed disruptions in the inferred microbiota functions in adolescent depression-associated microbiota, particularly in glycolysis and gluconeogenesis. Additionally, depressed adolescents exhibited systemic immune dysfunction, with elevated levels of pro-inflammatory cytokines and chemokines, which showed significant correlations with the differential genera. Our study bridges the gap between children and adults by providing new insights into the fecal microbiota characteristics and their links to immune system disruptions in depressed adolescents, which offer new targets for the diagnosis and treatment of depression in this age group.