136 Intestinal Barrier Function: Physiological Regulation, Injury, and Repair in Horses and Swine

Abstract Intestinal barrier function is critical to prevent translocation of microorganisms and their toxins from the intestinal lumen to the circulation. This is particularly noteworthy in horses, in which colic may be associated with ischemia and breakdown of the intestinal barrier, and in pigs, in which infectious diseases such as PEDv cause epithelial soughing and loss of intestinal barrier function. The term ‘function’ refers to the ability of a single layer of columnar epithelium that lines the intestinal tract to form a physical and dynamic barrier. This layer of epithelium is linked by a series of interepithelial junctions, most importantly tight junctions, that has to prevent passage of noxious luminal contents, while simultaneously serving to transport electrolytes, water, and nutrients necessary for physiological function of the host. The tight junctions are dynamically regulated by the cytoskeleton via nutrient signaling, and perturbed by reduced oxygen tension and pathogenic organisms. Barrier function also includes the ability to rapidly repair. In the small intestine, villus contraction is the initial phase of repair, followed by crawling of epithelium adjacent to the wound using a mechanism called restitution. In the colon, where there are no villi, restitution is particularly rapid. Following restitution, tight junctions have to be re-sealed to re-establish barrier function, which occurs rapidly by recycling intact tight junction proteins. The intestinal barrier is further disrupted during injury by inflammation, including transmigration of neutrophils that disrupt tight junctions. An additional critical element of barrier function is the continuous renewal of epithelium via proliferation of stem cells contained within the intestinal crypts. Proliferation increases following injury to replace lost epithelium. Collectively, barrier function includes mechanisms to maintain a healthy epithelial barrier, repair in the acute phases of injury and inflammation, and replace epithelium via stem cell activity.