Gut microbiota-targeted interventions for depression in adolescents and young adults: Mechanisms, evidence strength and clinical strategies-A narrative review.

Abstract

Depression in adolescents and young adults is common, associated with substantial functional impairment and characterised by limited treatment efficacy. The microbiota-gut-brain (MGB) axis has emerged as a potential therapeutic target for depression. This narrative review synthesises preclinical and clinical evidence on a range of MGB axis interventions aimed at alleviating depressive symptoms in youth, including probiotics, prebiotics, synbiotics, postbiotics, faecal microbiota transplantation (FMT) and lifestyle strategies such as dietary modification and structured exercise. In animal models, these interventions consistently produce antidepressant effects, accompanied by reduced inflammatory signalling, normalisation of hypothalamic-pituitary-adrenal axis activity and upregulation of neurotrophic and serotonergic pathways. In humans, particularly among younger cohorts, the evidence is heterogeneous. Some probiotic or synbiotic regimens have yielded modest improvements in depressive symptoms in preliminary trials, whereas stand-alone prebiotics have shown inconsistent or null effects; clinical evidence for postbiotics and FMT remains preliminary. Lifestyle interventions that target the MGB axis, such as Mediterranean-style diets and structured exercise programmes, have been associated with improved mood and, in some studies, reductions in inflammatory biomarkers. Compared with studies in adults, research in this population remains limited by small sample sizes, greater methodological heterogeneity and less consistent findings and also suggests the presence of age-specific pathways. Current evidence indicates that interventions targeting the MGB axis should be approached cautiously and considered only as adjunctive strategies for the treatment of depression in this population. Future work requires rigorously designed, strain- and protocol-specific clinical trials with standardised procedures, careful safety monitoring and biomarker-guided personalised approaches.