The use of linaclotide, a guanylate cyclase C (GC-C) agonist used in clinical practice to treat constipation-predominant IBS, restored both colonic hypersensitivity and permeability, proposing the GC-C/cGMP pathway as an important player in the peripheral regulation of the persistent visceral pain in adults exposed to this form of ELS (109). The gene discussed is GUCY2C; the disease is irritable bowel syndrome.