Colesevelam was previously found to suppress ileal Fgf15 expression due to its binding of bile acids, which subsequently derepresses hepatic Cyp7a1 expression via the Fxr–Fgf15–Cyp7a1 axis in a mouse model of high-fat diet-induced obesity [7], which we confirmed in our microbiome-humanized mice. Here, NR1H4 is linked to obesity due to melanocortin 4 receptor deficiency.