Role of Gut Microbiota in Major Depressive Disorders: A review

Abstract

Major Depressive Disorder (MDD), the fourth leading cause of disability, affects 350 million people globally and shares genetic overlap with psychiatric disorders like bipolar disorder and schizophrenia. Research suggests MDD is linked to increased levels of pro-inflammatory cytokines, including interleukin, indicating immune system involvement. Gut microbiota (GM) plays a crucial role in regulating the gut-brain axis, and gut dysbiosis can disrupt this axis, leading to the production of harmful metabolites, immune mediators, and pro-inflammatory cytokines. This negatively impacts neurotransmitter production, such as norepinephrine, serotonin (5-HT), and dopamine, all essential in mood regulation. Non-pharmacological approaches, including ketogenic diets, calorie restriction, and intermittent fasting, have been shown to protect and restore GM by improving intestinal barrier integrity and stimulating cell regeneration. A healthy GM strengthens tight junctions and encourages antimicrobial peptide production. Additionally, probiotics downregulate stress-induced ‘GABA’ mRNA expression in the amygdala and prefrontal cortex, reducing corticosterone levels. This helps prevent gut leakage, reverses stress-induced HPA axis activation, and shows promise in minimizing depressive thoughts and behaviors.