Development of a Weaned Pig Model of Enterotoxigenic E.coli-induced Environmental Enteropathy

Abstract

Environmental enteropathy is chronic inflammatory disease of the small intestine that hinders the childhood development in impoverished countries. As it assumes a large role in the malnutrition as well as stunting of growth in the early stages of life. This is correlated with an increased likelihood of contracting a chronic disease in adulthood. A specific culprit of the disease is unknown but it is assumed that an enteric pathogen plays a role as fecal-oral contamination and poor living conditions are the primary routes to infection. Weaned pigs experience similar symptoms to that of humans in a disease known as post weaning diarrhea. The aim of this study was to develop a model of environmental enteropathy that can be utilized for the research of new interventions. Twenty-four weaned piglets at approximately 14lbs were randomly assigned to one of three treatments. The pigs were housed 2 pigs per pen with a total of 4 pens per treatment. The treatments were as follows: 1) Control (sham challenged with PBS) 2) Acute (received one dose of ATCC 23545) and 3) Chronic (received a daily dose of ATCC 23545). After 2 d of acclimation, pigs were challenged with the respective treatment on d 1. Feed disappearance, body weight, blood and fecal samples were taken on d 0, 1, 3, and 6. Blood and fecal samples were analyzed for inflammatory markers. All pigs were necropsied on d 7 for the collection of intestinal samples for histology and determination of Enterotoxigenic Eschericia coli counts. The ETEC 23545 treatment had no effect on ADG, ADFI, or G:F throughout the duration of the trial (P≥.18 ) A treatment interaction was seen on d 6 serum levels of IL-6 (P<0.05) but an effect was not seen in the d 6 serum levels of IL-8. The fecal calprotectin levels did not have a treatment (P=.95) day (P=.48) or treatment x day (P=.95) effect. However, the fecal colony counts experienced a treatment effect (P<.0001). The acutely challenged pigs most closely mimicked environmental enteropathy in children with highest fecal shedding of E.coli, elevated colonization of small intestine and elevated levels of serum IL-6

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