Given the role of Se in antioxidant activity, its implication in chronic low grade inflammation during obesity, and the impact it might have on changes in the composition and function of intestinal microbial communities, we investigated how: 1) dietary variations of Se in combination with high or low-fat diets impact intestinal microbial populations, and 2) the intake of this mineral alters the host eCBome-mediated response and immune status as well as antioxidant activity exerted by selenoproteins in the intestinal microenvironment. This evidence concerns the gene SELENOS and obesity due to melanocortin 4 receptor deficiency.