Avaliação da dieta MAL-ED associada com desnutrição infantil na barreira morfofuncional do epitélio intestinal e recuperação da lesão com uso de glutamina em modelo murino

Abstract

Child malnutrition is considered a serious public health problem as it is associated with high mortality rates, cognitive and growth deficits. The use of translational preclinical models is essential for the search for more appropriate treatments and is important to reduce the morbidity associated with malnutrition. Therefore, the objective of this work was to evaluate the intestinal epithelial barrier function of mice subject to an animal model of acute malnutrition based on the complementary diet of children with malnutrition described in the MAL-ED multicenter COHORT study and to investigate whether treatment with glutamine reverses the changes caused. For the induction of experimental malnutrition, male C57BL/6 mice (21 days old) were fed the MAL-ED diet for 12 days. As a treatment, glutamine was used continuously (final concentration of 31.4 mM in drinking water) for five days, starting on the eighth day after starting the diet. Another group of animals received the same concentration of isonitrogenic glycine, to investigate the results found in glutamine treatment were caused by increased nitrogen levels. On days 0, 7 and 12 of the experimental protocol, body composition and body development were measured. The intestinal barrier function was measured using electrophysiological parameters of Potential Difference - DP, Short Circuit Current - Isc and Transepithelial Resistance - Basal Rt and absorption of glucose, glutamine, and alanyl-glutamine. Mice subjected to the MAL-ED diet showed a reduction in fat mass, weight gain, and body growth. The analyzes in automatized Ussing Chamber System (UCS) showed an increase in Rt in relation to the cumulative concentrations of glutamine and alanyl-glutamine, reducing the low absorption of substrates in animals that consumed the MAL-ED diet. Treatment with glutamine reversed weight loss and promoted improvement in body growth, an increase in basal Rt and an improvement in the intestinal epithelial barrier function in animals that consumed the MAL-ED diet. According to the findings of the present study, the MAL-ED diet causes changes in the gastrointestinal barrier. Furthermore, it demonstrated the use of glutamine as a new mechanism for effectiveness in improving weight gain and growth in malnourished animals by restoring the function of the intestinal epithelial barrier.