2nd Annual BMRP Investigator Meeting - Abstract

Dietary Calcium, Spermine or Tryptophan Supplementation Reduces Severity of Dextran Sulfate Sodium (DSS)-induced Colitis in Rats

Steven C. Hebert

Department of Cellular and Molecular Physiology, Yale University (New Haven, Connecticut, U.S.A.)

Background & Aims: The extracellular calcium-sensing receptor (CaSR) is an unusual G protein-coupled receptor that senses changes in extracellular concentrations of calcium and other nutrients such as polyamines and amino acids.  CaSR activation in the gastrointestinal tract leads to modulation of two important aspects of intestinal function: fluid absorption/ secretion, and cell proliferation/differentiation/apoptosis.  These functions are perturbed in patients with inflammatory bowel disease (IBD).   The present study invested CaSR function in a DSS model of IBD in rats.

Materials & Methods: Male adult Sprague-Dawley rats (100 gram) were given either a standard diet as control (C), standard diet supplemented with 2.5% (w/w) calcium (CA), 0.1% spermine (S) or 1% tryptophan (T), for three weeks; this was followed by adding 3% (w/v) dextran sulfate sodium (DSS) to drinking water to induce the IBD-like symptoms.  Daily body weight loss was recorded as well examining the development of bloody diarrhea as signs of induction of the IBD symptoms.  Following onset of weight loss and bloody diarrhea, animals were sacrificed and changes in colonic pathology were examined.

Results:

  • Bloody diarrhea, body weight loss and decreased colon weight and length developed in animals receiving (C) in response to DSS treatment.  The severity of the DSS-induced bloody diarrhea and accompanying weight loss was markedly reduced in animals receiving either calcium-(CA), spermine-(S) or tryptophan-(T) diets.  In these latter groups, no significant differences in both colon weight and length were noted between DSS-treated and non-DSS control animals.
  • Microscopically, a decrease in total number of crypts, reduction in crypt length, and the onset of ulceration was observed following DSS treatment in (C).  Groups receiving (CA), (S), or (T) diets had a marked reduction in severity of the morphological parameters observed in group (C).
  • Under DSS-free conditions, no significant differences in body weight, feces consistency and weight and length of colons were observed in CA, S, or T group animals and C group animals.  However, colonic mucosal hypertrophy occurred in animals of all supplement groups (CA, S, T) compared to controls.

Conclusion: Dietary supplementation of calcium, spermine or tryptophan may be beneficial in the prevention and/or treatment of IBD.  This effect may be exerted via modulation of the CaSR and its role in the proliferation and differentiation of intestinal epithelia.