Pre-/pro and synbiotics on anxiety and depression symptoms: a GRADE assessed systematic review and meta-analysis of randomized controlled trials

The influence of pre-/pro-/synbiotics on depressive and anxiety symptoms remains ambiguous. This systematic review and meta-analysis aimed to clarify the impact of these interventions on mental health outcomes in adults. A systematic search was conducted across PubMed, Scopus, and Web of Science databases until May 10, 2025, to identify randomized controlled trials (RCTs) evaluating the effects of pre-/pro-/synbiotics on depressive and anxiety symptoms in adults. Random-effects models were used to compute pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated using funnel plots and Egger’s test. A total of 70 RCTs (65 for depression and 49 for anxiety) met the inclusion criteria and had intervention durations ranging from 2 to 24 weeks. Pre-/pro-/synbiotics supplementation significantly reduced depressive symptoms (SMD = −0.57; 95% CI: −0.71, −0.43, p < 0.001; I2 = 83.0%) and anxiety symptoms (SMD = −0.43; 95% CI: −0.59, −0.28, p < 0.001; I2 = 80.5%). Subgroup analyses for depression revealed larger effects in studies with sample size < 50, and in participants aged ≥ 50 years. Probiotics and synbiotics significantly reduced depression, while prebiotics did not. All three intervention types significantly reduced anxiety, with synbiotics showing the largest effect. This meta-analysis suggests that supplementation with pre-/pro-/synbiotics may have beneficial effects on depressive and anxiety symptoms in adults. However, due to substantial heterogeneity and the overall moderate methodological quality of included studies, these findings should be interpreted with caution. Importantly, these interventions should be considered as an adjunctive option to support mental health, not as a replacement for standard evidence-based treatments such as pharmacotherapy and psychotherapy. Further high-quality RCTs with standardized protocols are warranted to confirm these findings and establish definitive clinical recommendations.