Gut microbiota dysbiosis in adolescent depression: a comparative analysis with adult depression and healthy adolescent.

Introduction: Adolescent depression differs substantially from adult depression in neurodevelopmental and pathophysiological aspects, with gut microbiota dysbiosis recognized as a key regulator via the microbiota-gut-brain axis. Nevertheless, the age-specific microbial and metabolic signatures of adolescent depression remain poorly defined. Methods: 125 participants including 33 adolescents with depression, 62 adults with depression, and 30 healthy adolescent controls were recruited. Full-length 16S rRNA gene sequencing was applied to profile gut microbial composition and functional metabolism. Results: Alpha diversity was markedly reduced in adolescents with depression relative to healthy adolescent, whereas no significant difference was observed between adolescent and adult depression. PCoA and age-adjusted PERMANOVA revealed distinct microbial community separation across the three groups, with disease status contributing substantially to community divergence. A significant Group × Age interaction indicated that depression may exerted age-dependent effects on gut microbiota. At the genus level, 19 differential taxa were identified between depressed and healthy adolescents, with Discussion: Our findings reveal both age-conserved and adolescent-specific microbial signatures, providing candidate microbial signatures and hypothesis-generating functional insights.