INTRODUCTION: Sleep disturbances are common and contribute to substantial functional and health-related burden. Probiotics have been proposed as a potential modulator of sleep via gut-brain axis mechanisms, yet the magnitude, consistency, and clinical significance of their effects remain uncertain. This study synthesized all randomized controlled trials evaluating the effect of probiotic supplementation on validated subjective and objective sleep outcomes, using harmonized change-score methodology and contemporary certainty-of-evidence grading.
METHODS: An updated search (March 31, 2022-October 1, 2025) was performed in PubMed, Scopus, and Web of Science to identify randomized placebo-controlled trials evaluating probiotics in adults or adolescents. Outcomes included global Pittsburgh Sleep Quality Index (PSQI) scores, PSQI subdomains, insomnia severity, objective sleep measures, and OSA Sleep Inventory MA (OSA-MA) factors. Effect sizes were synthesized as mean differences or standardized mean differences comparing change from baseline between probiotic and placebo groups. Random-effects models were used for all analyses.
RESULTS: Thirty-nine trials (n=4094 participants) were included. Probiotic supplementation significantly improved PSQI global scores (mean difference (MD) -0.71; 95% CI -1.23 to -0.20; very low certainty). Benefits were domain-specific, with significant improvements in daytime dysfunction (MD -0.08; 95% CI -0.11 to -0.05) and sleep time (MD 0.11; 95% CI 0.01 to 0.21), while other subdomains showed no consistent effects. Insomnia severity did not improve overall (SMD 0.17; 95% CI -1.15 to 1.49), although sensitivity analysis excluding an influential study indicated a significant reduction (standardized mean difference (SMD) -0.44; 95% CI -0.74 to -0.14; low certainty). Objective sleep outcomes showed modest improvements, including increased total sleep time (MD 13.82 minutes; 95% CI 1.15 to 26.49) and reduced awake time during sleep period (MD 5.15 minutes; 95% CI 0.43 to 9.87). Probiotics significantly improved OSA-MA Factor 1 (sleepiness on rising; MD 1.07; 95% CI 0.40 to 1.75) and Factor 4 (refreshing on rising; MD 1.18; 95% CI 0.42 to 1.94), with no significant differences in other factors.
CONCLUSIONS: Probiotic supplementation is associated with small improvements in global subjective sleep quality and selected subjective sleep domains. However, effect sizes are modest, certainty of evidence is generally low, and the clinical meaningfulness of these findings remains uncertain.
SYSTEMATIC REVIEW REGISTRATION: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000057556, identifier UMIN000050539.
Gut-Brain Axis