Chylomicron-responsive Tregs in EED

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Abstract. A quarter of the world’s children experience chronic malnutrition coupled with a lack of access to clean drinking water. This combination results in Environmental Enteric Dysfunction (EED), a disease where intestinal malabsorption exacerbates malnutrition, leading to increased cognitive deficiencies, stunted growth and mortality. The intestine of EED patients is characterized by inflammation and flattened villi in the small intestine that negatively affect absorptive capacity. Our groups have recently identified a pool of protective Tregs in the small intestine that respond specifically to dietary lipid absorption, to the presence or absence of chylomicrons secreted in response to dietary lipids, and to EED. We hypothesize that lipid absorption and chylomicron secretion is reduced in the EED intestine, that EED-chylomicrons deliver less dietary triglyceride to mesenteric LN Tregs, and that replenishing calories by bypassing the chylomicron pathway (with a medium-chain- triglycerides) will restore calories without blocking the effect EED-chylomicrons that will travel by the lymph to stimulate protective intestinal Tregs.