An updated systematic review and appraisal of the pathophysiologic mechanisms of probiotics in alleviating depression.

Gut-brain axis has emerged as a promising strategy for managing depression. Probiotic supplements, which modulate the gut microbiome, are suggested to enhance gut-brain communication and improve depressive symptoms and cognitive function. However, the acceptance of probiotics in managing depression remains contentious. This study aimed to evaluate the effects of probiotics on depression through meta-analysis and to assess their mechanisms of action, focusing on changes in gut microbial composition and neural mechanisms. A total of 12 randomized controlled trials from PubMed, Web of Science, and Scopus, up to January 1, 2024, were included. Nine studies consistently demonstrated improvements in depressive symptoms, gut microbiota, inflammatory markers, cognitive function, and mood regulation. The meta-analysis indicated a significant reduction in depressive symptoms with probiotics compared to placebo, with a mean difference of - 1.94 (95% CI = -3.56 to - 0.32,  = 0.02, I = 69%). The Hamilton Depression Rating Scale (HAM-D), which showed substantial improvement, with a mean difference of - 3.27 (95% CI = -6.42 to - 0.12,  = 0.04, I = 82%), is a preferred tool for further studies due to its comprehensive symptom coverage and strong psychometric properties. Probiotic strains such as subspecies JYLP-326 and CCFM1025 were particularly effective, while multi-strain probiotics generally showed more consistent effects than single-strain interventions. Probiotics show promising potential in alleviating depression through their anti-inflammatory effects, gut microbiota modulation, cognitive function enhancement, and possible influence on brain structure and neurotransmitter systems. Despite some variability in trial results, this review provides updated insights for medical practitioners, highlighting probiotics as a viable treatment option for depression.