Concurrently, it is worth noting that FSDSS-treated organoids displayed a strong downregulation of Fstl4 mRNA, coding for a protein that negatively regulates BDNF maturation, thus its biological effect.127 It is well documented that BDNF and other neurotrophins are involved in chronic pain establishment,128,129 especially in abdominal pain related to IBS.130–135 However, only one study reported that blocking the BDNF signaling ameliorated visceral hypersensitivity in an IBS-like rat model.136 Moreover, no therapeutic strategies to modulate epithelial-derived BDNF have been developed so far. The gene discussed is FSTL4; the disease is irritable bowel syndrome.