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P079. Effects of a mixture of amino acids on colonic mucosa healing after experimental colitis

X. Liu1, M. Baumont1, J.-C. Marie2, C. Chaumontet1, M. Andriamihaja1, F. Walker2, H. Matsumoto3, D. Tomé1, A.-M. Davila1, F. Blachier1, 1Institut National de la Recherche Agronomique (INRA), AgroParisTech, Centre de Recherche en Nutrition Humaine-Ile de France, UMR 914 Physiologie de la Nutrition et du Comportement Alimentaire, Paris, France, 2Institut National de la Santé et de la Recherche Médicale (INSERM) Université Paris 7 Denis Diderot, U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, Paris, France, 3Institute for Innovation, Ajinomoto Co. Inc, Frontier Research Laboratory, Kawasaki, Japan

Background

Mucosal healing (MH) is considered today as an important goal for the treatment of inflammatory bowel diseases as well as an end point for clinical trials. During the process of healing, the colonic mucosa has specific requirements in terms of energy, carbon and nitrogen sources. MH is believed to require increased supply in some amino acids. The objective of this study was to test the impact of specific amino acids supplementation (Thr, Met and Glu) on colonic MH using DSS-induced colitis rat model.

Methods

Experimental colitis was induced in Wistar male rats by the ingestion of 5% (w/v) DSS in drinking water for 6 days (baseline data). The rats with colitis induced were thus randomly assigned to 2 different groups. One received the amino acids mixture (AA) (Thr 0.5 g/j, Met 0.31 g/j and Glu 0.57 g/j) and the other received alanine (0.86 g/j) as iso-nitrogenous control in drinking water for 3, 7 or 10 days. At each time point, colonic luminal contents were collected for water content measurement and distal segments of colon were sampled for histopathology studies, myeloperoxidase activity and glutathione content measurements, and for IL-1beta, TNF-alpha, IL-6, IL-10, MIP-2, TGF-beta, MUC-2 and MUC-3 gene expression assessment.

Results

At baseline (after 6d DSS treatment), the colonic luminal water content, MPO activity, pro-inflammatory cytokines, regulatory cytokines and the percentage of inflammatory surface of colonic mucosa were significantly higher in DSS-treated rats. After 7d of AA treatment, the colonic luminal water content was significantly lower (71.5%+/-1.7%) comparing to the control group (77.4%+/-1.2%) (p < 0.05), indicating an amelioration of the overall absorptive function of the colon. After 10d of AA treatment, the percentage of regeneration and reepithelialization of the colonic mucosa was significantly higher (81%+/-7%) compared to the control group (51%+/-8%) (p < 0.05), indicating an improvement of the colonic MH.

Conclusion

Our study points out a beneficial effect of specific amino acids supplementation in the colonic MH (structure and functionality) after experimental colitis in rats. Our results also provide data on the evolution of all parameters for the establishment of a set of criteria that could be utilized for the monitoring of post-DSS healing phase in this experimental model. Further work is needed to confirm the effects of Thr, Met and Glu on MH in clinical trials.