A New Murine Undernutrition Model Based on Complementary Feeding of Undernourished Children Causes Damage to the Morphofunctional Intestinal Epithelium Barrier

Complementary feeding is critical in establishing undernutrition. However, experimental undernourished diets do not represent the amount of nutrients in the complementary diets of undernourished children. To develop, validate, and evaluate the impact of a new murine model of undernutrition on the in...

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Bibliographic Details
Published in:	The Journal of nutrition Vol. 154; no. 4; p. 1232
Main Authors:	Ribeiro, Samilly A, Braga, Enock Lr, Queiroga, Marcus L, Clementino, Marco A, Fonseca, Xhaulla Mqc, Belém, Mônica O, Magalhães, Lyvia Mvc, de Sousa, José K, de Freitas, Thiago M, Veras, Herlice N, de Aquino, Cristiane C, Santos, Alan Dc, de Moura, Flávio Rm, Dos Santos, Armênio A, Havt, Alexandre, Maciel, Bruna Ll, Lima, Aldo Am
Format:	Journal Article
Language:	English
Published:	United States 01-04-2024
Subjects:	Animals Child Child Nutrition Disorders - complications Cohort Studies Disease Models, Animal Humans Infant Infant Nutritional Physiological Phenomena Intestinal Mucosa - metabolism Malnutrition - complications Mannitol Mice Mice, Inbred C57BL Zinc undernutrition experimental model child undernutrition body composition complementary feeding functional barrier of the intestinal epithelium
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Summary:	Complementary feeding is critical in establishing undernutrition. However, experimental undernourished diets do not represent the amount of nutrients in the complementary diets of undernourished children. To develop, validate, and evaluate the impact of a new murine model of undernutrition on the intestinal epithelium, based on the complementary diet of undernourished children from 7 countries with low-socioeconomic power belonging to the Malnutrition-Enteric Diseases (MAL-ED) cohort study. We used the difference in the percentage of energy, macronutrients, fiber and zinc in the complementary diet of children without undernutrition compared with stunting (height-for-age Z-score < -2) for the MAL-ED diet formulation. Subsequently, C57BL/6 mice were fed a control diet (AIN-93M diet) or MAL-ED diet for 28 d. Weight was measured daily; body composition was measured every 7 d; lactulose:mannitol ratio (LM) and morphometry were evaluated on days 7 and 28; the cotransport test and analysis of intestinal transporters and tight junctions were performed on day 7. The MAL-ED diet presented -8.03% energy, -37.46% protein, -24.20% lipid, -10.83% zinc, +5.93% carbohydrate, and +45.17% fiber compared with the control diet. This diet rapidly reduced weight gain and compromised body growth and energy reserves during the chronic period (P < 0.05). In the intestinal epithelial barrier, this diet caused an increase in the LM (P < 0.001) and reduced (P < 0.001) the villous area associated with an increase in FAT/CD36 in the acute period and increased (P < 0.001) mannitol excretion in the chronic period. The MAL-ED diet induced undernutrition in mice, resulting in acute damage to the integrity of the intestinal epithelial barrier and a subsequent increase in the intestinal area during the chronic period. This study introduces the first murine model of undernutrition for the complementary feeding phase, based on data from undernourished children in 7 different countries.
ISSN:	1541-6100
DOI:	10.1016/j.tjnut.2024.02.001