A. R. Munoz1, S. R. Hamarneh1, H. Albadawi2, M. Watkins2, F. Adiliaghdam1, J. M. Ramirez1, F. Kuehn1, R. Hodin1 1Massachusetts General Hospital,Department Of Surgery,Boston, MA, USA 2Massachusetts General Hospital,Division Of Vascular And Endovascular Surgery,Boston, MA, USA
Introduction: Ulcerative colitis (UC) is characterized by a chronic increase of intestinal pro-inflammatory cytokines. The brush-border enzyme intestinal alkaline phosphatase (IAP) functions as an anti-inflammatory factor, and its levels are decreased in UC patients. Furthermore, IAP supplementation has been shown to be protective against colitis in mice and humans. Recently, attention has been drawn to the potential benefits of exercise on UC. We thus sought to study the effect of exercise on colitis development, while also investigating the potential role of IAP in the pathway.
Methods: Seven week old C57BL/6 mice were either exercised (EX) or not exercised (NX) for 4 weeks (n=6). Exercised mice were placed on a treadmill for 1 hour daily with 12 m/min speed and 10º incline. Stool was collected daily and used for pNPP phosphatase activity assays and bacterial colony quantification plating. Following the 4-week period, mice were treated with either 2% dextran sodium sulfate (DSS) or normal drinking water for 7 days (n=3). After the 7-day treatment, mice were all placed on normal drinking water for 2 days. Mice were then weighed to determine percent weight loss during DSS treatment and were gavaged with FITC for intestinal permeability determination. Five hours after gavage, mice were sacrificed and serum FITC levels were determined.
Results: After the 4-week exercise period, the EX group weighed less than the NX group (23.38±0.40 vs 26.17±1.05 g, p=.033), demonstrating exercise efficacy. Additionally, the EX group showed significantly increased IAP activity (299.19±30.76 vs 167.82±30.40 pmole pNPP hydrolyzed/min/ug protein, p=.038) and increased levels of aerobic bacterial colonies (440,133±93,597 vs 108,800±40,754 CFU/g stool, p=.0088). In response to the DSS exposure, EX mice lost less percent body weight compared to NX mice (7.3±2.1 vs 22.6±3.7 percent body weight loss, p=.024), indicating less severe colitis in the EX group. Furthermore, the EX mice maintained a healthier gut mucosal barrier, i.e., less FITC fluorescence in serum following DSS-treatment (569.9±199.3 vs 1376.3±26.2 fluorescence, p=.015).
Conclusion: Exercise appears to be protective against the development of colitis in mice, perhaps mediated in part by an upregulation of endogenous IAP.