Major depressive disorder (MDD) is a mental illness with high mortality, suicide, and relapse rates that could become the leading cause of health problems worldwide by 2030. The microbiota-gut-brain axis involves bidirectional communication between the human gut microbiota and the central nervous system (CNS). The gut microbiome is a complex ecosystem of approximately 100 trillion microorganisms, including viruses, bacteria, and fungi. The gut microbiota has recently been recognized for its impact on various diseases and health concerns. Several factors influence the composition and structure of gut microbes, ultimately affecting human physiology, with the nervous system being particularly vulnerable. The gut-brain-microbiota axis influences several important brain functions through numerous pathways, including vagus nerve signaling, gut microbial synthesis of metabolites, and immune-related chemicals. These factors can influence neurotransmitter activity, neuroinflammation, behavior, and mental health. Despite increased interest, the possibility of modifying the gut microbiota as a therapeutic approach remains unclear. Although numerous studies suggest that microbiota play an important role in many illnesses, the precise mechanisms are yet to be elucidated, and there are currently no evidence-based, microbiota-focused treatments for these illnesses. Recent research indicates that gut dysbiosis (GD) causes increased intestinal permeability (leaky gut), initiates systemic inflammation, and contaminates the blood. Opportunistic microbial metabolites cross the blood-brain barrier, triggering a neuroinflammatory cascade and apoptotic pathways while affecting neurogenesis and neurotransmitters, ultimately resulting in the development of MDD and anxiety. This review examined the factors influencing normal gut microbiota and GD-mediated MDD, as well as possible therapeutic options. The study outlines its objectives and methodological approaches, including the screening and filtering of research on GD-induced depression. Furthermore, it explored the daily use of dietary supplements, revealing new paths for clinical and preclinical research.
