One month of NS8 supplementation alleviated the depression-like behaviors of WKY rats; improved gut microbiota composition and function; reduced the levels of CRH in the hippocampus; increased the levels of GR, DA, and BDNF in the hippocampus; and alleviated the abnormalities in the serotonergic system and noradrenergic systems (Figure 8, graphic abstract). Here, NR3C1 is linked to major depressive disorder.