A heat-stable toxin made by certain E. coli strains works by overstimulating a gut receptor called guanylate cyclase-C, flooding the intestine with fluid. Researchers wondered whether a safer, engineered version of the same signal could treat the opposite problem, chronic constipation.
In a 12-week randomized trial of 800 adults with irritable bowel syndrome with constipation, those taking the synthetic peptide linaclotide daily saw significantly more complete bowel movements than those on placebo, with 33.6 percent meeting the FDA's combined response criteria compared with 21 percent on placebo.
Because linaclotide barely leaves the gut and does not reach the bloodstream in meaningful amounts, it avoids most of the systemic side effects older constipation drugs carried. The main downside reported was diarrhea in a subset of patients, and the drug works on symptoms rather than on any underlying cause of the disorder.
Read the original study
Rao et al., American Journal of Gastroenterology, 2012 · doi.org/10.1038/ajg.2012.255
A diarrhea toxin, redesigned to treat constipation.
Source
- Rao, S., Lembo, A. J., Shiff, S. J., Lavins, B. J., Currie, M. G., Jia, X. D., Shi, K., MacDougall, J. E., Shao, J. Z., Eng, P., Fox, S. M., Schneier, H. A., Kurtz, C. B., & Johnston, J. M. (2012). A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation. The American Journal of Gastroenterology, 107(11), 1714–24; quiz p.1725. https://doi.org/10.1038/ajg.2012.255