Supplemental calcium attenuates the colitis-related increase in diarrhea, intestinal permeability, and extracellular matrix breakdown in HLA-B27 transgenic rats.
We have shown in several controlled rat and human infection studies that dietary calcium improves intestinal resistance and strengthens the mucosal barrier. Reinforcement of gut barrier function may alleviate inflammatory bowel disease (IBD). Therefore, we investigated the effect of supplemental calcium on spontaneous colitis development in an experimental rat model of IBD. HLA-B27 transgenic rats were fed a purified high-fat diet containing either a low or high calcium concentration (30 and 120 mmol CaHPO4/kg diet, respectively) for almost 7 wk. Inert chromium EDTA (CrEDTA) was added to the diets to quantify intestinal permeability by measuring urinary CrEDTA excretion. Relative fecal wet weight was determined to quantify diarrhea. Colonic inflammation was determined histologically and by measuring mucosal interleukin (IL)-1beta. In addition, colonic mucosal gene expression of individual rats was analyzed using whole-genome microarrays. The calcium diet significantly inhibited the increase in intestinal permeability and diarrhea with time in HLA-B27 rats developing colitis compared with the control transgenic rats. Mucosal IL-1beta levels were lower in calcium-fed rats and histological colitis scores tended to be lower (P = 0.08). Supplemental calcium prevented the colitis-induced increase in the expression of extracellular matrix remodeling genes (e.g. matrix metalloproteinases, procollagens, and fibronectin), which was confirmed by quantitative real-time PCR and gelatin zymography. In conclusion, dietary calcium ameliorates several important aspects of colitis severity in HLA-B27 transgenic rats. Reduction of mucosal irritation by luminal components might be part of the mechanism. These results show promise for supplemental calcium as effective adjunct therapy for IBD.
Schepens
Marloes A A
MA
TI Food and Nutrition, 6700 AN Wageningen, The Netherlands.
Schonewille
Arjan J
AJ
Vink
Carolien
C
van Schothorst
Evert M
EM
Kramer
Evelien
E
Hendriks
Thijs
T
Brummer
Robert-Jan
RJ
Keijer
Jaap
J
van der Meer
Roelof
R
Bovee-Oudenhoven
Ingeborg M J
IM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002118:Calcium / Q000494:pharmacology / Q000627:therapeutic use*; D002136:Calcium, Dietary / Q000494:pharmacology / Q000627:therapeutic use*; D003092:Colitis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003967:Diarrhea / Q000188:drug therapy* / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000008:administration & dosage / Q000652:urine; D005109:Extracellular Matrix / Q000187:drug effects*; D005243:Feces; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015796:HLA-B27 Antigen / Q000235:genetics; D053583:Interleukin-1beta / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010539:Permeability / Q000187:drug effects; D011347:Procollagen / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic
D000893:Anti-Inflammatory Agents; D002136:Calcium, Dietary; D005353:Fibronectins; D015796:HLA-B27 Antigen; D053583:Interleukin-1beta; D011347:Procollagen; D004492:Edetic Acid; D020782:Matrix Metalloproteinases; D002118:Calcium