The efficacy of probiotics, prebiotics, and synbiotics on anxiety, depression, and sleep: a systematic review and meta-analysis of randomized controlled trials.

backgroundWith the growing recognition of the limitations associated with conventional treatments for anxiety and depression, there has been increasing interest in alternative and adjunct therapies, particularly probiotics, prebiotics, and synbiotics. However, current research results regarding their efficacy in treating anxiety, depression, and sleep have been inconsistent.

methodsA systematic literature search for randomized controlled trials (RCTs) was conducted in PubMed, Web of Science, and Embase from inception to October 2023, updated in March 2025. The included studies involved individuals with anxiety and depression disorders, or chronic disease patients/healthy populations presenting with depressive or anxiety symptoms. Two researchers independently screened and extracted data. The Cochrane risk of bias tool was used to evaluate the quality of the included studies. Data synthesis and subgroup analyses were performed in Review Manager 5.3 and Stata 15.0 software. The anxiety, depression, and sleep scores were calculated by the standard mean difference (SMD) and 95% confidence intervals (CIs).

resultsA total of 72 RCTs were included (3,319 intervention and 2,778 control participants). Among these, researchers examined depression in 63 studies (2,880 and 2,493 participants) and anxiety in 49 studies (2,124 and 1,788 participants) using probiotics/prebiotics/synbiotics interventions, while 12 studies (411 and 378 participants) examined sleep using probiotic interventions. The meta-analysis demonstrated significant reductions compared to placebo in depression (SMD = − 0.53, 95% CI: −0.67 to − 0.39, Z = 7.33, P < 0.001) and anxiety (SMD = − 0.44, 95% CI: −0.59 to − 0.28, P < 0.001). Additionally, probiotics were shown to improve sleep quality (SMD = − 0.39, 95% CI: −0.53 to − 0.25, P < 0.001). Subgroup analyses indicated that both probiotics, prebiotics, and synbiotics independently alleviated anxiety and depression. The impact of probiotics varied by population, intervention duration, and probiotic types.

conclusionThese findings suggest that probiotics, prebiotics, and synbiotics offer promising adjunctive treatments for anxiety, depression, and sleep disturbances. However, given the high heterogeneity and limited methodological quality of the included studies, further large-scale and high-quality RCTs with long-term follow-up are needed to further validate these outcomes. REGISTRATION: The protocol was registered on PROSPERO (Registration number: CRD42024563862). CLINICAL TRIAL NUMBER: Not applicable.