Optimization of a small intestinal segment perfusion model for heat-stable enterotoxin A induced secretion in pigs

Abstract

Enterotoxigenic Escherichia coli (ETEC) are a major cause of infectious diarrhea both in human and pigs. After ingestion of contaminated food or water, ETEC bacteria colonize the small intestine where they produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, which induce watery diarrhea. We investigated the possibility of eliciting STa-induced secretion in jejunal segments of anesthetized pigs using a small-intestinal segment perfusion (SISP) model. Five consecutive mid-jejunal segments of anaesthetized piglets were perfused for 6h with different concentrations of STa in a physiologic salt solution. Changes in intestinal net fluid absorption were measured. From the results we could conclude that the STa response was dose-dependent and that continuous perfusion with 50nM of STa or more was required to reduce net absorption. This concentration was sufficient to reduce net absorption compared to control segments in 12 out of 14 piglets. STa-induced responses however showed relative high variation between different jejunal segments of one pig, similar to the inter-segment variation seen in control animals where segments were perfused with physiologic salt solution. These results indicate that more optimization is required before this model could be used to test compounds that could interfere with the STa-induced fluid secretion.