Dietary heme adversely affects experimental colitis in rats, despite heat-shock protein induction.
OBJECTIVE
Research on dietary modulation of inflammatory bowel disease is in its infancy. Dietary heme, mimicking red meat, is cytotoxic to colonic epithelium and thus may aggravate colitis. Alternatively, heme-induced colonic stress might also result in potential protective heat-shock proteins (HSPs). Therefore, we investigated the effect of dietary heme on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.


METHODS
Rats were fed a high-fat control diet or a similar diet supplemented with heme. After dietary adaptation, rats were rectally infused with TNBS for colitis induction or saline for sham treatment. Colitis severity was evaluated and several markers were quantified in colonic mucosa isolated 1 wk after colitis induction. Furthermore, cytotoxicity of fecal water and serum α-1-acid glycoprotein were measured.


RESULTS
Dietary heme increased cytotoxicity of the fecal water. Heme-fed sham-treated rats had higher colonic HSP-25 and heme-oxygenase-1 mRNA levels, which was confirmed by immunohistochemistry. HSP induction by heme was associated with decreased protein levels of myeloperoxidase and interleukin-1β after subsequent TNBS infusion. However, no dietary effects were observed on histologic colitis score. Furthermore, body weight gain, colon length, and food intake were lower and α-1-acid glycoprotein concentrations were higher in heme-fed colitic rats. In addition, somatostatin, involved in mucosal repair, was not changed with TNBS infusion in heme-fed rats.


CONCLUSIONS
Dietary heme adversely affects colitis, despite HSP induction. We speculate that the irritating influence of dietary heme, being continuously present in the colon, impairs recovery after colitis induction. A diet high in red meat might be a risk factor for inflammatory bowel disease development.
Schepens
Marloes A A
MA
Top Institute Food and Nutrition, Wageningen, The Netherlands.
Vink
Carolien
C
Schonewille
Arjan J
AJ
Dijkstra
Gerard
G
van der Meer
Roelof
R
Bovee-Oudenhoven
Ingeborg M J
IM
D000818:Animals; D015415:Biomarkers; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004754:Enterobacter / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006418:Heme / Q000009:adverse effects*; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced*; D053583:Interleukin-1beta / Q000032:analysis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007777:Lactobacillaceae / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D015415:Biomarkers; D006360:Heat-Shock Proteins; D053583:Interleukin-1beta; D006418:Heme; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D051547:Heme Oxygenase-1