Probiotics as a Tool for Regulating Molecular Mechanisms in Depression: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Depression is one of the main mental disorders. Pharmacological treatment of depression is often associated with delayed effects or insufficient efficacy. Consequently, there is a need to discover new therapeutic methods to cope with depression faster and more effectively. Several lines of evidence indicate that the use of probiotic therapy reduces depressive symptoms. Nonetheless, the exact mechanisms linking the gut microbiota and the central nervous system, as well as the potential mechanisms of action for probiotics, are still not entirely clarified. The aim of this review was to systematically summarize the available knowledge according to PRISMA guidelines on the molecular mechanisms linking probiotics and healthy populations with subclinical depression or anxiety symptoms, as well as depressed patients with or without comorbid somatic illnesses. The standardized mean difference (SMD) with 95% confidence intervals (CI) was calculated. Twenty records were included. It has been found that probiotic administration is linked to a significant increase in BDNF levels during probiotic treatment compared to the placebo (SMD = 0.37, 95% CI [0.07, 0.68], = 0.02) when considering the resolution of depressive symptoms in depressed patients with or without comorbid somatic illnesses. CRP levels were significantly lower (SMD = -0.47, 95% CI [0.75, -0.19], = 0.001), and nitric oxide levels were significantly higher (SMD = 0.97, 95% CI [0.58, 1.36], < 0.0001) in probiotic-treated patients compared to the placebo, however, only among depressed patients with somatic co-morbidities. There were no significant differences in IL-1β, IL-6, IL-10, TNF-α, and cortisol levels after probiotic administration between the intervention and control groups (all > 0.05). Firm conclusions on the effectiveness of probiotics and their possible association with inflammatory markers in the healthy population (only with subclinical depressive or anxiety symptoms) cannot be drawn. The advent of clinical trials examining the long-term administration of probiotics could evaluate the long-term effectiveness of probiotics in treating depression and preventing its recurrence.