In a chronic unpredictable stress model of murine depression, a synbiotic combination of L. plantarum ATCC 793 (Lp793), B. longum ATCC 15707 (Bl15707), and a botanical-derived polyphenolic preparation (BDPP) promoted CTLA4+ Treg expansion, lowered Th17 cells in the gut, lowered IL-1β and IL-17a levels in the serum, and lowered prefrontal cortex IL-1β levels, which attenuated depression and anxiety-like behaviors [376]. This evidence concerns the gene CTLA4 and major depressive disorder.