Dr. Jake Sallaway-CostelloMAY SALEH ALOTAIBI2022-05-262022-05-26https://drepo.sdl.edu.sa/handle/20.500.14154/29972Abstract Background: Depression is amongst the most common mental disorders and is often related to a number of other medical conditions. Accumulating evidence suggests that probiotics can be efficient in decreasing depressive symptoms. Objective: The current systematic review aimed to evaluate the effectiveness of probiotic supplementation on depressive symptoms, inflammatory biomarkers and markers of hypothalamic–pituitary–adrenal (HPA) axis, and to evaluate the safety of probiotics supplementation in MDD patients (≥16) years. Methodology: A systematic search of the literature of 4 databases (MEDLINE, Cochrane Library, PubMed and Embase) for full text English-language papers published from 2015 to 2020, was carried out, and followed the principles of Preferred Reporting Items for Systematic Reviews and Meta-analyses. Randomised controlled trials that investigated the effects of probiotics on depressive symptoms in patients (≥16) with MDD, were eligible. The independent t-test was performed to compare the mean difference between groups. Results: In total, six RCTs with a total sample of 333 participants were included. Probiotics supplementation shows a significant reduction in depressive symptoms compared with placebo [SMD= -1.208, 95% C.I (-1.44─ -0.975), P=0.01]. No significant change was shown in inflammatory biomarkers TNF-α (-1.11±8.87 vs. 3.2±4.43, P=0.11); IL-6 (-562892.66± 974959.77 vs. -153412.01±265718.13, P=0.26); IL-1β (0.32±0.48 vs. 0.28±0.48, P=0.4); CRP (-154.35± 1392.08 vs. 534.20± 489.04, P=0.29), and the markers of HPA axis in kynurenine (-0.13±0.13 vs. 0.087±0.08, P=0.09), tryptophan (-0.53±7.3 vs. -1.23±1.87, P=0.45); Cortisol (- 13.10±18.49 vs. -13.28±18.81, P=0.4). However, no significant adverse effects were noted in the probiotics group compared with the control group. Conclusion: Overall, probiotics supplementation showed a beneficial impact on depressive symptoms without significant adverse effects in MDD patients. However, probiotics had no significant influence on inflammatory biomarkers and markers of HPA axis. Further RCTs on adolescents with MDD are needed, and specific recommendations are required for the use of probiotics in clinical practice in patients with MDD. Keywords: Major depressive disorder (MDD), probiotics, gut-brain axis, depressive symptoms, inflammatory biomarkers, HPA axis.en