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

  • 2025-09-04
  • Frontiers in nutrition 12
    • Haitao Liu
    • Xiaoli Li
    • Ying Shi
    • Ke Hong
    • Xing Wang
    • Congfu Huang

Study Design

Type
Review
Population
Adolescent depression affects 13% of youths globally, with 30-40% exhibiting treatment resistance.
Methods
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).

Background

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.

Methods

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).

Results

Depressed adolescents showed reduced gut microbiota α-diversity (Shannon index SMD = -0.92; 95% CI: -1.24, -0.60) and altered taxa abundance (e.g., Bacteroidetes depletion: Δ = -32%). Dysbiosis correlated with anhedonia severity (r = 0.42; 95% CI: 0.28, 0.55) and impaired social functioning. Psychobiotics (e.g., Lactobacillus plantarum PS128) 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: Bifidobacterium breve 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.

Conclusion

Gut microbiome modulation shows promise as an adjunct to behavioral therapies (e.g., CBT). Bifidobacterium breve's female-predominant effects suggest hormonal modulation. Future research must address gaps in FMT safety, developmental mechanisms, personalized nutritional interventions.

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