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.
Hanchen Hou, Yinan Li, Wanting Tang et al.· General Psychiatry· 0 citations
Abstract Background Adolescence is a critical period for brain network remodeling and the onset of major depressive disorder (MDD); however, white matter (WM) functional topology in adolescent MDD remains underexplored. Given that WM functional signals reflect meaningful neural activity and are disrupted in psychiatric disorders, this study aimed to characterize WM functional connectome alterations in adolescents with MDD and examine their clinical associations. Methods Resting-state fMRI data were obtained from a cohort of adolescents with MDD (n = 320) and healthy controls (HCs, n = 144), as well as from an independent replication cohort. Following the construction of thresholded WM functional networks, graph-theoretical analyses were used to calculate global topological properties. Canonical correlation analysis (CCA) was used to examine associations between topology and clinical symptoms, while exploratory classification assessed their discriminative information and generalizability. Furthermore, subgroup analyses were conducted to evaluate the effects of a history of suicide attempt, non-suicidal self-injury, childhood trauma, and sex. Results Compared with HCs, adolescent MDD exhibited significant reductions in the clustering coefficient, characteristic path length, and local efficiency. CCA identified distinct covariation patterns: reduced global integration was linked to severe suicidal ideation and depressed mood, while impaired local segregation was associated with vegetative symptoms such as weight loss and insomnia. Subgroup analyses revealed significant sexual dimorphism, with male patients demonstrating more severe topological impairments than females. A similar pattern was observed in the independent replication cohort. The classification analysis achieved above-chance accuracy (69.6 and 60% in the two cohorts). Conclusions Our results reveal a topologically shifted WM functional connectome structure in adolescent MDD, providing new clues to aid in understanding the pathophysiology of its pathophysiology.
