Efeitos imunobiológicos de dietas contendo aminoácidos livres

Abstract

Nutrients are capable of modulating the immune system in several ways, including the development and maintenance of immune homeostasis. After weaning, dietary proteins are essential for the maturation of the gut-associated lymphoid tissue (GALT) and modulation of systemic immune activity, such as response to infection, nasal and oral tolerance induction and allergic responses. In situations of immunological maturity, in adult animals, the role of dietary protein in the immune system is not known. To understand the immune effects of diets containing free amino acids (AA) is very important in clinical routine, especially in situations of intestinal inflammation in which elemental diets containing AA are used. Nutritional therapy is a commonly used complementary tool in the treatment of inflammatory bowel disease, but there is no consensus about the most appropriate dietary formulation. Thus, the objective of this study was to analize the immunobiological effects of diets containing either free amino acids (AA diet) or intact proteins (casein) in adult animals in physiological conditions as well as during intestinal inflammation. In all experimental protocols, 8 week-old mice C57BL/6 were chosen. AIN93 diet containing either 15% casein (CAS diet) or equivalente amounts of AA (AA diet) were used. For evaluation analysis in physiological conditions, animals received either CAS or AA diet for five weeks. AA diet consumption did not change weight or biochemical tests indicative of nutritional status, however it lead to several immunobiological changes in mice, such as reduction of serum immunoglobulins and increase of several cytokines in the small intestine and colon, including IL-17, IL-10 and TGF- . Conversely, there was a reduction of virtually all cytokines evaluated in spleen of AA-fed mice. These alterations were observed mainly after one week of diet consumption. Animals form the amino acid group also showed an increase of total cells, activated cells, Th17 and regulatory T lymphocytes in the lamina propria of the small intestine, but not in the colon. In this case, differences among the groups were seen later, particularly after five weeks. Intestinal morphology was altered in the AA group, including increase of villus size and crypth depth in the small intestine and increase of cellular infiltration, reduction of globlet cells and edema of the submucosal layer in the colon. The impact of AA diet consumption also was evaluated in inflammatory situations. In this case, AA and CAS diets were offered either during the development of colitis induced by dextran sulfate sodium (DSS) or prior to colitis induction. AA diet caused exacerbation of intestinal inflammation when consumed previously and during colitis induction. This was evidenced by the increased clinical and histological scores and shortening of the colon in AA-fed mice. In conclusion, consumption of diets containing free AA to replace the intact proteins does not change the nutritional status, but causes several intestinal and systemic immunological changes in adult animals. Severity of these changes are proportional to the time of diet consumption. Presence of free amino acids in the diet causes exacerbation of intestinal inflammation. Thus, the use of diets containing free amino acids should be used with caution in clinical practice, specially during intestinal inflammation.