Gut-brain axis in adolescent depression: a systematic review of psychological implications and behavioral interventions.

Abstract

<h4>Background</h4>Adolescent depression affects 13% of youths globally, with 30-40% exhibiting treatment resistance. Emerging evidence implicates gut microbiome dysbiosis in core behavioral symptoms (e.g., anhedonia, social withdrawal) via gut-brain axis (GBA) pathways. This systematic review synthesizes clinical and preclinical evidence (2014-2025) to delineate the microbiota-behavior interactions and evaluate microbiome-targeted interventions.<h4>Methods</h4>Following PRISMA 2020 guidelines, 45 studies (29 clinical trials, 11 animal models, 5 meta-analyses) were analyzed from PubMed, Web of Science, and Embase. Data extraction focused on microbiome composition, neurobehavioral outcomes, and intervention efficacy. Random-effects meta-analyses pooled effect sizes (95% CIs).<h4>Results</h4>Depressed adolescents showed reduced gut microbiota <i>α</i>-diversity (Shannon index SMD = -0.92; 95% CI: -1.24, -0.60) and altered taxa abundance (e.g., <i>Bacteroidetes</i> depletion: Δ = -32%). Dysbiosis correlated with anhedonia severity (<i>r</i> = 0.42; 95% CI: 0.28, 0.55) and impaired social functioning. Psychobiotics (e.g., <i>Lactobacillus plantarum PS128</i>) significantly reduced depressive symptoms (HAM-D Δ = -4.2; 95% CI: -5.1, -3.3) vs. placebo and improved emotion recognition (+18%; 95% CI: 2.1, 33.9). Sex-specific effects were prominent: <i>Bifidobacterium breve</i> enhanced reward responsiveness in females (SMD = 0.61; 95% CI: 0.22, 1.00). Current data lack large-scale RCTs for fecal microbiota transplantation (FMT) in adolescents.<h4>Conclusion</h4>Gut microbiome modulation shows promise as an adjunct to behavioral therapies (e.g., CBT). <i>Bifidobacterium breve</i>'s female-predominant effects suggest hormonal modulation. Future research must address gaps in FMT safety, developmental mechanisms, personalized nutritional interventions.