Pathogenic disease modulation of pig intestinal function and integrity

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Helm, Emma
Major Professor
Gabler, Nicholas K
Burrough, Eric R
Loving, Crystal L
Koltes, Dawn A
Greiner, Laura L
Committee Member
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Animal Science
One key aspect of disease physiology that has garnered much attention in the swine industry over the last 10 years is that of “gut health”, which comprises many factors, including that of intestinal barrier permeability and digestive function. The ability of the gastrointestinal tract to regulate nutrient, energy, and water uptake into the body is critical for supporting efficient lean tissue accretion. However, pathogen induced disease often compromises gastrointestinal function, reducing efficient lean tissue accretion and overall health. As porcine pathogens have many different mechanisms of action, it is likely that individual pathogens have different implications on barrier function and permeability. Therefore, the overarching aim of this dissertation was to evaluate intestinal function and integrity of pigs during a variety of physiological stressors. We conducted 4 research chapters using disease models including Porcine Reproductive and Respiratory Syndrome Virus (PRRSV; Chapter 2), Brachyspira hyodysenteriae (Chapters 3 and 4), and Lawsonia intracellularis (Chapter 5) experimental challenges, as well as during a feed restriction event (Chapter 2). The PRRSV challenge was chosen in concert with the feed restriction (pair-feeding) model as we have developed a PRRSV model that consistently produces severe disease and complete loss of appetite. Chapters 3-5 focused on enteric pathogens. In post-nursery pigs (i.e. grow-finisher pigs), two common bacterial pathogens are B. hyodysenteriae and L. intracellularis. These two bacterial agents cause disease by different mechanisms, so we postulated they would not impact intestinal function and integrity in the same manner. Second to this primary objective, we evaluated potential prevention/mitigation strategies (diet manipulation and vaccination) during these pathogenic disease challenges to understand what positive impacts they may have on parameters of intestinal health, function, and integrity. Herein, we reported that a PRRSV challenge attenuated markers of intestinal integrity via the reduction of jejunal transepithelial resistance (TER), but this did not coincide with increased macromolecule permeability which is typically associated with reduced intestinal integrity (Chapter 2). Furthermore, these changes appear to primarily be caused by disease associated reductions in feed intake (Chapter 2). Conversely, B. hyodysenteriae challenge was not associated with any change to ileal permeability and was associated with increased TER and reduced macromolecule permeability (Chapter 3). Finally, L. intracellularis challenge was associated with no change to either TER or macromolecule permeability in the ileum or colon (Chapter 5). In Chapter 2, we evaluated small intestinal mRNA abundance, protein abundance, and cellular location of several tight junction proteins to determine if that explained the observed reduction in TER due to PRRSV and pair-feeding. Although we observed reductions in mRNA abundance of several tight junction proteins, no change to protein abundance or cellular location of these proteins was observed (Chapter 2). Thus, the reduction in TER due to PRRSV and pair-feeding was likely not driven by changes to tight junctional complexes, which would explain why no change to paracellular macromolecule permeability were observed. Regardless, unlike some pig pathogens such as PEDV, none of the challenge models utilized in the current experiment appear to dramatically reduce small or large intestinal epithelial barrier integrity. Also critical to intestinal health is maintenance of digestive and absorptive machinery. In Chapter 2, we found that PRRSV and disease hypophagia do not appear to reduce the digestive function of the intestinal tract, suggesting caloric supplementation may be a viable avenue to research regarding improving growth of PRRSV challenged pigs. However, digestive function was reduced by both B. hyodysenteriae (Chapter 3) and L. intracellularis (Chapter 5), albeit via different mechanisms. In the case of B. hyodysenteriae, this was likely driven by excessive watery diarrhea and mucus secretion, while in the case of L. intracellularis it was due to the failure of epithelial cells to mature into enterocytes. The ability of the gastrointestinal tract to maintain structural integrity and digestive function, before, during, and after stress events is imperative for supporting optimal pig growth performance, health, and wellbeing. Therefore, the ultimate goal of understanding intestinal physiology during different diseases is to develop the best prevention, mitigation, or recovery strategies to allow for increased growth and reduced mortality in the face of disease challenge. In this dissertation, we evaluated two strategies: dietary fiber manipulation (Chapters 3 and 4) and vaccination (Chapter 5). We demonstrated that replacing lowly fermentable fibers with highly fermentable fibers protected pigs from developing SD during B. hyodysenteriae challenge, potentially due to a reduction in species of anaerobic or mucolytic bacteria. We were also able to demonstrate that vaccination mitigated peak clinical disease during L. intracellularis challenge (Chapter 5), due to an earlier immune response and lower pathogen burden at peak infection. Taken together, this dissertation provides fundamental data regarding the impact various swine disease challenges have on intestinal function and integrity. Further, we evaluated several strategies that worked to mitigate disease, highly fermentable fibers in the case of B. hyodysenteriae and vaccination for L. intracellularis. This data provides pork producers with implementable strategies if they are experiencing problems with either pig pathogen. Finally, this dissertation highlights that not all pig pathogens induce “leaky gut” in pigs and attempts to improve intestinal integrity during these pathogen challenges may not be a particularly useful strategy to mitigate disease.