REVIEW article
Front. Nutr.
Sec. Nutrition, Psychology and Brain Health
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1644245
Gut-Brain Axis in Adolescent Depression: A Systematic Review of Psychological Implications and Behavioral Interventions
Provisionally accepted
- Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, China
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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) versus 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.
Keywords: adolescent depression, gut-brain axis, psychobiotics, mediterranean diet, personalized nutrition, microbiota, sex differences
Received: 11 Jun 2025; Accepted: 20 Aug 2025.
Copyright: © 2025 Liu, Li, Shi, Hong and Congfu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huang Congfu, Longgang District Maternity & Child Healthcare Hospital of Shenzhen City, Shenzhen, China
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