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Pathophysiological Effects of Brachyspira Species on Ion Transport Within the Porcine Colon Resulting in Diarrheal Disease



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Swine dysentery, a production limiting diarrhea in swine, is responsible for profound economic loss annually. Brachyspira hyodysenteriae is the etiological agent responsible for colonization of the colon and development of classical swine dysentery. Like Brachyspira hyodysenteriae, Brachyspira hampsonii causes mucohemorragic diarrhea which is indistinguishable from swine dysentery. Classical swine dysentery has been characterized as a malabsorptive diarrhea in which Na+ and Cl- absorption is abolished in diarrheic pigs. However, characterization of the transporters responsible for these alterations in ion transport have not been studied. Thus, this thesis focuses on the pathophysiological mechanisms involved in altering the colonic mucin environment and the alterations in ion transport responsible for the development of diarrheal disease. Both secretory and absorptive responses were characterized in the colon of experimentally challenged pigs infected with Brachyspira hyodysenteriae or Brachyspira hampsonii. Anion secretion was assessed in Ussing chambers by measuring short-circuit current following agonist addition. Additionally, 22Na and 36Cl radiolabelled isotope fluxes in Ussing chambers were used to assess changes in unidirectional and net ion transport. 3H-mannitol radiolabelled isotope fluxes were also used to assess barrier function. Changes in ion channel and transporter mRNA and protein expression in the colon of diseased pigs was assessed by RT-qPCR and western blot. To determine the role of cytokines on modulation of ion channel and transporter function RT-qPCR was used to assess gene transcripts throughout the porcine colon. Finally, to provide a mechanism for the alterations in ion transport, Caco-2 monolayers were exposed to both cytokines and a Brachyspira hampsonii lysate. Anion secretion along with Na+ and Cl- absorption was significantly reduced in the colon of diarrheic pigs infected with Brachyspira hyodysenteriae and Brachyspira hampsonii, with no change in epithelial barrier function. This response was attributed to a decrease in channel and transporter mRNA and protein. The only cytokine significantly up-regulated throughout the colon of diseased pigs out of the 12 cytokines examined was IL-1α. IL-1α was responsible for the decrease in the anion exchanger DRA mRNA but, not chloride channel CFTR or the cation exchanger NHE3 mRNA expression as indicated by Caco-2 monolayers exposed to human recombinant IL-1α for 24 hours. Interestingly, Caco-2 monolayers exposed to a Brachyspira hamspsonii lysate had significantly reduced mRNA expression of both CFTR and NHE3 after 48 hours of exposure accompanied by a significant increase in IL-1α expression. I conclude, that although the observed decrease in anion secretion would not contribute to diarrheal development, it would begin to explain some of the pathophysiological changes in mucin rheological properties observed within the colon. These changes in the colonic mucin environment benefit Brachyspira species allowing for greater growth and colonization. On the other hand, the significant decrease in Na+ and Cl- absorption in the colon of diarrheic pigs due to loss of NHE and DRA mRNA and protein define the pathophysiological mechanism by which this malabsorptive diarrhea develops. These changes in ion transport are attributed to both the host’s cytokine response and direct effects of Brachyspira species.



Swine, Diarrhea, Ussing chamber, Ion transport, Ion channels



Doctor of Philosophy (Ph.D.)


Veterinary Biomedical Sciences


Veterinary Biomedical Sciences


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