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). This evidence concerns the gene GUCY2C and constipation disorder.