Although the epigenetic mechanism of probiotics seems indirect and remains largely unexplored, the butyrate-producing bacterial strains which target HDAC inhibition either at the hippocampal level or the intestinal epithelial, modulating BDNF expression and proinflammatory cytokines with anti-depressive effects, may serve as a suitable probiotic candidate to facilitate a better understanding of the epigenetic role and potential of probiotics in treating depression. This evidence concerns the gene BDNF and major depressive disorder.