| Intestinal dysbiosis leads to immune dysregulation, nutritional deficiencies and chronic inflammatory diseases, therefore the relationship between host-derived antimicrobials and establishment of the microbiome is an important area of study. A significant contributor to forming an adult-like microbiome in mammals is the first diet, milk, owing in part to its antimicrobial enzymes. To better mimic human milk composition, we have genetically engineered goats to produce an increased concentration of human lysozyme (hLZ) in their milk to 67% of the level of human milk. Using the pig as a model organism for the human gastrointestinal tract, hLZ milk fed to young pigs resulted in changes to architecture of the small intestine and modulation of microbial populations, but the mechanism by which hLZ asserts these effects are unknown.;Peptidoglycan recognition proteins (PGLYRPs) are innate immune antimicrobials implicated in early establishment and maintaining the symbiotic equilibrium of commensal populations in a broad range of species. In humans and pigs there are four isotypes of PGLYRPs with PGLYRP-3 and 4 having highest expression throughout the gastrointestinal tract. Due to PGLYRPs function, the effect of hLZ on PGLYRP-3 and 4 expression and secretion is being investigated as a mechanism by which hLZ milk asserts its effects. To better understand this interaction, a pig jejunal cell line, IPEC-J2, was treated with hLZ milk which showed a subsequent time-dependent significant increase in expression of PGLYRP-3 and 4. Furthermore, PGLYRP-3 expression increased significantly in response to two commensal species, Bifidobacterium longum subp suis and Lactobacillus reuteri in a time-dependent manner. Thus, I demonstrate that milk from lysozyme transgenic goats induced expression of PGLYRP-3 and that this expression was also influenced by the presence of commensal bacteria. The goal of this work is to investigate how lysozyme and peptidoglycan recognition proteins (PGLYRPs) together help maintain an anti-inflammatory environment in the gut and determine if the mechanism involves modulating the microbiome. These studies are the basis for understanding how hLZ elevating PGLYRPs can help establish the microbiota in early life and potentially restore equilibrium after injury. |
