In experiments in apolipoprotein E-deficient (ApoE−/−) mice with hypercholesterolemia and atherosclerosis susceptibility induced with a high-fat diet, Haghikia et al. [116] identified a novel regulatory pathway in which propionate acts as a prebiotic to selectively regulate the immune system in the gut, resulting in a reduction in the aortic atherosclerotic lesion area and the control of intestinal cholesterol homeostasis. Here, APOE is linked to familial hypercholesterolemia.