Regional Differences in Stress-Induced Increase of Epithelial Permeability in the Mouse Intestine

Background and Aims: Stress is known to increase intestinal permeability, which may contribute to the development of irritable bowel syndrome (IBS) and other intestinal disorders. However, regional differences in epithelial permeability along the intestinal tract and their responses to stress have yet to be explored. Methods: Adult male and female C57BL/6 mice were utilized to compare the regional permeability differences amongst sex and their responses to stress. Mice in the stressed groups were placed in restrainers for one hour per day for five days as a form of stress. Control mice remained in their primary cage without undergoing restraint stress. Following the last stress/control session, the duodenum, jejunum, ileum, proximal colon, and distal colon were removed, and the mucosa/submucosa preparations were mounted onto the Ussing Chamber System. Transepithelial resistance (TER) was recorded as a measurement of paracellular permeability. FITC-insulin (4kD) and horseradish peroxidase (HRP, 40 kD) were added to the luminal chamber, and the flux rates from luminal to basolateral side were used to assess the paracellular and transcellular permeability, respectively. Results: Stress resulted in a significant decrease in TER only in the distal colon of male and female mice. FITC-insulin flux rate remained unaffected by stress in male mice but was significantly increased in the distal colon of the stressed female mice. HRP flux rate was significantly increased in the proximal colon of the stressed males while showing no significant change in the female intestinal tract. Conclusions: The results suggest that the large intestinal epithelium is more vulnerable to stress comparing to the small intestine, and male and female mice respond differently to stress. Aiming toward the specific regions impacted by stress may aid in the creation of regional-specific medications that more specifically target IBS or other stress-related gut problems. University of Wisconsin-La Crosse Faculty Research Grant (SL) and Undergraduate Research and Creativity Grant (LB & LV) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.