Investigations on the Prospects of Using Lactiplantibacillus plantarum to Combat Depression through Gut Microbiota–Brain Axis

Depression is a common neurological disorder that causes a substantial burden of disease due to higher mortality and prevalence rates. The gut microbiota plays a major role in mood regulation and offers novel insights into the etiology and management of depression. However, gut dysbiosis has a negative impact on mood, cognition, behavior, and brain development. Therefore, approaches to restore the normal gut composition, such as probiotics, prebiotics, and fecal microbiota transplant, may offer novel tactics to improve therapy for depression, among which probiotics have drawn significant attention as a therapeutic intervention. Although there is no consensus on the most effective probiotic strain for treating depression, Lactiplantibacillus plantarum (L. plantarum) has gained considerable prominence due to its therapeutic potential in managing depression. The mechanisms by which L. plantarum regulates depression involve modulating the gut–brain axis through the production of various compounds, including gamma-aminobutyric acid (GABA), tryptophan, lactate, short-chain fatty acids (SCFAs), acetylcholine, and vitamins. This review highlights the antidepressant potential of L. plantarum through modulation of the gut microbiota and explores the possible mechanism of action of L. plantarum and its metabolites, as well as the genetic and epigenetic regulation of host responses and potential microRNA interactions that modulate the gut microbiota. Furthermore, metabolic engineering techniques for the L. plantarum strain, as well as promising strategies for delivering L. plantarum to the brain, have been discussed. A deeper insight into the mechanisms and gut microbiota interventions may provide effective treatment approaches for depression.