Effects of consumption of milk containing recombinant human lactoferrin and lysozyme on porcine immunity in models of health and disease

Human milk helps protect and promote maturation of the gut and mucosal immune system in infants. Abundant human milk proteins, including lactoferrin and lysozyme, help confer these positive health effects of human milk. Cows and goats normally produce low levels of lactoferrin and lysozyme in their milk, however there are transgenic cattle which produce high amounts of recombinant human lactoferrin (rhLF-milk) and goats which produce high levels of human lysozyme in their milk (hLZ-milk). Pigs were utilized to study the effects of consumption of rhLF-milk and hLZ-milk because pigs have similar gastrointestinal physiology to humans. This current research demonstrates the positive effects of consuming rhLF-milk and a combination of rhLF-milk and hLZ-milk in healthy pigs as well as the efficacy of using hLZ-milk as a treatment for E. coli induced diarrhea in pigs. Compared to control goats' milk, the hLZ-milk was a more effective treatment for diarrhea. Pigs consuming hLZ-milk recovered from clinical signs of infection faster with significantly improved fecal consistency and activity level, and circulating immune cells returned faster to pre-infection level, while control-fed pigs had significantly higher hematocrit indicating dehydration. In the ileum, pigs fed hLZ-milk had significantly less damaged villi and lower expression of pro-inflammatory cytokine IL-8. These data demonstrate that hLZ-milk is a more effective treatment of E. coli-induced diarrhea than control milk. When comparing rhLF-milk fed pigs to control-milk fed pigs we observed that rhLF-milk beneficially changed circulating leukocyte populations and gastrointestinal morphology. There was proportionally a significant decrease in neutrophils and increase in lymphocytes and changes in intestinal villi architecture including longer villi, deeper crypts, and thinner lamina propria. Effects of consumption of rhLF-milk and hLZ-milk separately and in combination was tested and compared to control milk. Pigs fed rhLF+hLZ milk had significantly deeper intestinal crypts and a thinner lamina propria layer. Pigs fed hLZ-milk, rhLF-milk, and rhLF+hLZ had significantly reduced mean corpuscular volume and increased red blood cells. These results align with previous research and suggest that in some parameters the combination of lactoferrin and lysozyme have additive effects, in contrast to the synergistic effects reported when utilizing in-vitro models.