Chronic constipation is among the most common sources of morbidity affecting health care expenditures and quality of life in the developed world. In striking contrast, diarrheal disease continues to be a leading cause of morbidity and mortality in underdeveloped countries. In a metamorphosis from pathogenetic mechanism to therapeutic paradigm, linaclotide, a first-in-class 14-amino acid peptide homologous to bacterial heat-stable enterotoxins (STs; Figure 1A) contributing to global endemic diarrhea, is emerging as a promising agent to treat chronic constipation. In this issue of Gastroenterology, a Phase IIb US, multicenter, double-blind, placebo-controlled trial revealed that linaclotide was well-tolerated and improved symptoms, bowel function, and disease-relevant quality-of-life measures in patients with chronic constipation.
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