Major depressive disorder (MDD) is a disturbing mental condition affecting millions of people globally. The gut microbiota has garnered a major attention in the neurobiology and treatments of brain disorders, including depression. In this systematic review, we emphasized how prebiotics, probiotics, synbiotics, and postbiotics treatments manage depression. We registered this review on the Open Science Framework platform (Registration number: osf.io/bu674). As per PRISMA guidelines, we obtained 224 preclinical and clinical studies from five electronic databases (PubMed, Medline, EMBASE, Cochrane Library, and Web of Science) for the period of December 2008 to February 2025. Pan-probiotic approaches showed superior mood-elevating effects compared to a single-strain intervention. The mechanistic investigations of these studies unveiled complex neuroendocrine alterations, including the increase in serotonergic neurotransmission, anti-inflammatory responses, brain-derived neurotrophic factor expression, microbial diversity, and normalization of cortisol. Lactobacillus and Bifidobacterium genera exhibited the most consistent antidepressant-like effects at 1-10 billion colony-forming units (CFU) administered for 8-10 weeks. The probiotic and prebiotic interventions also demonstrated beneficial effects across the diverse clinical subpopulations, including patients with comorbid gastrointestinal disorders, heart complications, metabolic disorders, and postpartum depression. While these findings underscore the potential of microbiota-targeted therapeutics in depression, large-scale and long-term clinical trials are needed to identify a precise probiotic strain and treatment regimen.
Keywords: Clinical; Depression; Gut microbiota; Prebiotics; Preclinical; Probiotics; Synbiotics.
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