Our findings further strengthen the indication of FXR-FGF19-based therapies in the clinical management of chronic intestinal inflammation and CRC in patients with concomitant dysregulation of BA homeostasis, possibly due to unhealthy eating patterns leading to intestinal dysbiosis and comorbidities, such as obesity and type 2 diabetes. Here, FGF19 is linked to obesity due to melanocortin 4 receptor deficiency.