Probiotic bacteria are widely accepted as therapeutic agents against inflammatory bowel diseases for their immunostimulating effects. In the last decade, more evidence has emerged sup-porting the positive effects of probiotics on the course of neurodegenerative and psychiatric diseases. This brief review summarizes the data from clinical studies of probiotics possessing antidepressant properties and focuses on the potential genes and proteins underlying these mechanisms. Data from small-sample placebo-controlled pilot studies indicate that certain strains of bacteria can significantly reduce the symptoms of depression, especially in depressed patients. Despite the disparity between studies attempting to pinpoint the bacterial putative genes and proteins accounting for these mecha-nisms, they ultimately show that bacteria are a potential source of metabiotics—microbial metabolites or structural components. Since the constituents of cells—namely, secreted proteins, peptides and cell wall components—are most likely to be entangled in the gut–brain axis, they can serve as starting point in the search for probiotics with concrete properties.