The role of gut microbiota in adolescent depression: Insights from adverse childhood experiences.

BACKGROUNDDepression has become a leading global mental health disorder, with a rising prevalence of 15-20 % among adolescents. Emerging evidence suggests that adolescent depression may constitute a distinct subtype, differing clinically and neurobiologically from adult presentations. The gut microbiota's role in psychiatric disorders has garnered increasing attention, as dysbiosis may modulate behavior and mood via the microbiota-gut-brain axis, potentially contributing to depressive pathogenesis.

METHODSThis study included 60 depressed and 64 healthy adolescents (aged 11-18). Fecal samples were immediately flash-frozen in liquid nitrogen after collection, stored at -80 °C within 30 min, and processed within 6 months to minimize DNA degradation. And microbial DNA was extracted using the HiPure Stool DNA Mini Kit. The V3-V4 hypervariable regions of the 16S rRNA gene were amplified via PCR with primers 341F (5'-CCTAYGGGRBGCASCAG-3') and 805R (5'-GACTACHVGGGTATCTAATCC-3'), followed by Illumina NovaSeq 6000 sequencing. PCR cycle optimization was performed via gradient testing (20-30 cycles), confirming 25 cycles as optimal to prevent chimera formation while maintaining amplicon yield. Bioinformatics pipelines included QIIME2 for quality filtering, DADA2 for ASV inference, and PICRUSt2 for functional prediction. Statistical analyses included t-tests, mediation analysis, and Linear discriminant analysis Effect Size (LEfSe).

RESULTSFifty percent of depressed adolescents originated from single-parent or grandparent-led households and exhibited reduced resilience scores alongside elevated adverse childhood experiences (ACEs). Gut microbiota analysis revealed significant compositional and functional dysbiosis in depressed youth, marked by depletion of beneficial taxa (e.g., Bifidobacterium, Faecalibacterium) and butyrate-producing species, alongside enrichment of pro-inflammatory genera (e.g., Escherichia-Shigella). Mediation analyses implicated ACEs as a potential driver of these microbial alterations.

CONCLUSIONSThis study reveals distinct gut microbiota profiles in adolescents with depression compared to healthy controls, offering mechanistic insights into how ACEs and microbial dysbiosis may contribute to depressive etiology.