| Description |
Promoting intestinal epithelial regeneration remains a major medical challenge. Interestingly, there is a sexually distinct wound healing response to consumption of nonsteroidal anti-inflammatories (NSAIDs). We mined the literature for NSAID patient data finding that female patients taking NSAIDs are less likely to have acute damage to the intestine than males. We verified in vivo that female mice recover faster than male mice following drug-induced acute intestinal epithelial damage by scoring enteritis symptoms and performing histological staining on sectioned tissue. Using an ex vivo organoid system we showed that estrogen is necessary and sufficient in enhancing female organoid formation via estrogen receptor beta. Thus, estrogen promotes female intestinal epithelial organoid regeneration to lower the incidence of intestinal bleeding and ulceration. The intensive and prolonged usage of NSAIDs remains a dominant treatment strategy for many diseases including cancer and arthritis. With distillation of dosage, mechanistic explanation and approved clinical trials, estrogen supplementation holds promise to minimize gastrointestinal side effects for patient groups subject to chronic NSAID treatment. It is paramount to separate these beneficial, protective intestinal effects from the feminizing effects of estrogen to make this treatment viable for all patient populations. In total, these experiments demonstrate estrogen to be partially responsible for a more robust healing of the female intestinal epithelium. |
