Journal of Nutrition

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© 2007 American Society for Nutrition J. Nutr. 137:2475-2480, November 2007


Nutritional Immunology

Low Dietary Calcium Levels Modulate Mucosal Caspase Expression and Increase Disease Activity in Mice with Dextran Sulfate Sodium–Induced Colitis1–3,

Laetitia C. Pele4,5, Vinay Thoree5, Feras Mustafa5, Shijun He5, Loukia Tsaprouni6, Neville A. Punchard6, Richard P. H. Thompson5, Stephen M. Evans5 and Jonathan J. Powell4,*

4 MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge CB1 9NL, UK; 5 Gastrointestinal Laboratory, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, UK; and 6 Division of Science, University of Luton, Luton LU1 3JU, UK

* To whom correspondence should be addressed. E-mail: jonathan.powell{at}mrc-hnr.cam.ac.uk.

Dietary calcium (Ca) positively modulates the susceptibility to colon cancer, but its effects on related or earlier colonic pathologies, such as inflammation and mucosal dysregulation, are poorly understood. We tested the effects of differing dietary Ca levels on acute dextran sulfate sodium (DSS)-induced colitis in mice. BALB/c mice received a normal Ca (NCa) diet (0.5% Ca), a high Ca (HCa) diet (1.5% Ca), a low Ca (LCa) diet (0.05% Ca), or a very low Ca (VLCa) diet (0.009% Ca) for 3 wk. Mucosal caspases 1, 3, and 9 were assessed by Western blotting, and the histological crypt score was assessed by microscopy. Half of the mice in each group received DSS (1.5%) for 20 d in their drinking water, and disease activity was assessed. Increasing or lowering dietary Ca increased mucosal caspases (P < 0.0001 vs. NCa). Crypt scores increased with decreasing dietary Ca levels (P < 0.0001, r = –0.675), indicating that elevated caspases in LCa groups reflected early subclinical inflammation. DSS-induced disease activity was higher in mice fed low dietary Ca levels [P < 0.0001, VLCa and DSS vs. NCa and DSS (NCaDSS) and P < 0.005, LCa and DSS vs. NCaDSS], and mice from the VLCa group were moribund within 11 d of DSS administration. Those in the HCa group did not differ greatly from controls. Together, these data indicate that Ca protects against DSS-induced colitis in mice. The mechanisms are unclear, but the calcium-sensing receptor and/or luminal precipitates of calcium phosphate microparticles may be involved. Whether these observations can be extended to patients with colitis or infectious diarrhea deserves consideration.








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