Schematic model of the microbiota gut-brain axis: An interplay between the HPA axis, the immune system, the gut microbiome and the brain connected by biomolecules. This figure shows the complex communication between the gut (bottom) and the brain (top) with a wide array of factors inducing, promoting, and inhibiting the stress (top right) and immune system (middle left) with an important role for the gut microbiota and microbial derivatives (bottom). Microbiota can be (indirectly) bidirectionally involved with a hyperactive HPA axis and pro-inflammatory state that play a role in the etiology of MDD. ACTH, adrenocorticotropic hormone; BBB, blood-brain barrier; BDNF, brain-derived neurotrophic factor; CORT, cortisol; CRH, corticotropin-releasing hormone; CVO, circumventricular organs; LPS, lipopolysaccharide; MAMPs, microbe-associated molecular patterns; NTs, neurotransmitters (serotonin, dopamine and norepinephrine); SCFAs, short-chain fatty acids; TJP, tight junction protein; TLR4, toll-like receptor 4; TRP, tryptophan; TYR, tyrosine; Dashed line in BBB: impaired BBB integrity; Dashed in in gut epithelial barrier: leaky gut.