The gut microbiome's influence on brain function and mental health is a burgeoning area of research. Adolescence is considered a sensitive period for gut-brain axis development, making dietary interventions potentially impactful on long-term mental health. Preclinical and human studies suggest that psychobiotics (probiotics and prebiotics) might offer a novel treatment avenue for anxiety. Probiotics, live bacteria, can release neuroactive substances like GABA and serotonin. Prebiotics, non-digestible food ingredients, selectively stimulate beneficial bacteria. Animal studies demonstrate the psychotropic effects of probiotics and prebiotics, affecting anxiety-related behaviors and stress responses, particularly during adolescence. This review aims to assess the current evidence for the efficacy of psychobiotics in reducing anxiety and stress in young people aged 10–24 years.

The introduction extensively reviews preclinical and human studies exploring the gut-brain axis and the potential of psychobiotics to treat anxiety. Animal models have shown that manipulating gut microbiota via probiotics (e.g., *Lactobacillus* species, *Bifidobacterium* species) and prebiotics (e.g., fructooligosaccharides, galactooligosaccharides) can influence anxiety-like behaviors and stress responses. Adolescence is highlighted as a critical period for gut-brain axis development, making interventions during this stage potentially more impactful. Studies cited demonstrate that probiotics and prebiotics can affect GABA, serotonin levels and modulate stress responses in animal models, suggesting potential mechanisms for their anxiolytic effects. However, the translation of these findings to humans remains uncertain and requires further investigation.

This systematic review and meta-analysis followed PRISMA guidelines. Six databases (PubMed, Embase, Cochrane, Scopus, Ovid, Web of Science) were searched for controlled trials (May 30 – June 10, 2020) involving youth (10–24 years) with anxiety as a primary or secondary outcome. Inclusion criteria included controlled trials with at least one active treatment (probiotic or prebiotic) and one comparator group. Exclusion criteria were synbiotic interventions, unpublished data, and duplicate publications. 5416 studies were initially identified, with 14 eligible for systematic review and 10 for meta-analysis. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool (RoB-2). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Sensitivity analyses were performed excluding high-risk-of-bias studies.

Fourteen studies were included in the systematic review, nine involving probiotics and five prebiotics. Ten studies were included in the meta-analysis. The meta-analysis revealed no significant overall effect of psychobiotics on anxiety (pooled SMD = −0.03, 95% CI: −0.21, 0.14), indicating an absence of effect. Heterogeneity was 12%. Sensitivity analysis, accounting for risk of bias (one study low risk, five high risk, four uncertain), yielded a SMD of −0.16 (95% CI: −0.38, 0.07), suggesting minimal efficacy. Individual studies showed mixed results, with some suggesting a potential benefit for specific probiotic strains (e.g., *L. casei Shirota*) on stress reduction, but not anxiety. Several studies involved university students undergoing exam stress, focusing on stress-related GI problems or immune performance, and varied widely in the specific strains used, dosages, and outcome measures. In contrast to the meta-analysis findings which found no significant effect, one study showed improvement in worrying symptoms (high daily dose of probiotics). Two studies reported adverse effects (increased anxiety scores and pulse rate). Prebiotic interventions were less investigated but showed potential in some studies.

The findings of this systematic review and meta-analysis do not support the widespread use of psychobiotics for anxiety treatment in youth. The lack of a significant overall effect suggests that the current evidence is insufficient to recommend psychobiotics as a routine treatment for anxiety. The heterogeneity across studies highlights the need for standardized methodologies, including consistent outcome measures and well-defined doses and strains of psychobiotics. The observed minimal efficacy in sensitivity analysis may reflect true limited effectiveness, or it could be due to methodological limitations of the included studies. Further research is needed to determine which strains of probiotics and prebiotics are most effective for which symptoms and patient populations. The study's focus on adolescents and inclusion of youth consultation provides valuable insight into the acceptability of such interventions for this population. Future research should prioritize mechanistic studies in human models to establish causal relationships, and consider the wider context influencing the gut-brain axis.

Currently, limited evidence supports the use of psychobiotics for anxiety treatment in youth. Future research should adopt a multidisciplinary approach, focusing on mechanistic studies, standardized protocols, and the broader context impacting the gut-brain axis. This would help clarify the potential role of psychobiotics in managing anxiety and other mental health challenges in young people.

The study's limitations include the heterogeneity of studies in terms of psychobiotic types, dosages, outcome measures, and study populations. The relatively small number of studies included in the meta-analysis may have limited the statistical power to detect small effects. Risk of bias varied across studies, potentially influencing the results. Furthermore, the review primarily focused on anxiety, and other mental health outcomes were not consistently assessed. Future research needs to address these limitations to provide more robust evidence on the efficacy of psychobiotics.