Compelling preclinical data demonstrated the beneficial effect of probiotics in normalizing HPA axis functioning, BDNF levels and 5-HT neurotransmission. In particular, certain probiotics such as lactobacilli and bifidobacteria can reverse psychological stress-induced HPA axis activation and possess antidepressant or anxiolytic activity in rats. A seminal work in experimental animals showed that altered stress responsiveness has been partially reversed by colonization of the gut. Importantly, a recent and innovative study showed that short-term consumption of mostly animal or mostly plant diet rapidly and reproducibly altered the human gut microbiome, suggesting that the development of dietary interventions may provide a novel promising adjuvant therapy in addition to pharmacological antidepressant treatments in MDD. Indeed, recent reports of trials administrating a combination of probiotics to healthy subjects demonstrated improvements in depression or anxiety outcome measures. Moreover, urinary free cortisol levels were significantly reduced by the probiotics, providing a potential mechanism for the improvement in psychological symptoms observed. Consistent with this finding, other studies in healthy subjects found that the consumption of a probiotic-containing yogurt improved mood and that a multispecies probiotic (different strains of lactobacilli and bifidobacteria) reduced rumination and aggressive thoughts. Moreover, a pioneer study in healthy subjects revealed by using fMRI that consumption of probiotic bacteria (including strains of lactobacilli and bifidobacteria) in fermented milk for 4 weeks modulated brain activation in corticolimbic regions while viewing frightened and angry facial expressions. Most important, a very recent study demonstrated that administration of probiotics, a mixture of lactobacilli and bifidobacteria, ameliorated depressive symptoms in unmedicated patients with mild to moderate depression. These studies together suggest that restoring disturbed gut microbiome-brain interactions via probiotic bacteria might be a desirable treatment strategy for depression, especially as most of the clinically depressed patients additionally suffer from obesity, weight loss or gain, appetite disturbances and constipation.