Lysozyme transgenic goats’ milk positively impacts intestinal cytokine expression and morphology

Abstract

In addition to its well-recognized antimicrobial properties, lysozyme can also modulate the inflammatory response. This ability may be particularly important in the gastrointestinal tract where inappropriate inflammatory reactions can damage the intestinal epithelium, leading to significant health problems. The consumption of milk from transgenic goats producing human lysozyme (hLZ) in their milk therefore has the potential to positively impact intestinal health. In order to investigate the effect of hLZ-containing milk on the inflammatory response, young pigs were fed pasteurized milk from hLZ or non-transgenic control goats and quantitative real-time PCR was performed to assess local expression of TNF-α, IL-8, and TGF-β1 in the small intestine. Histological changes were also investigated, specifically looking at villi width, length, crypt depth, and lamina propria thickness along with cell counts for intraepithelial lymphocytes and goblet cells. Significantly higher expression of anti-inflammatory cytokine TGF-β1 was seen in the ileum of pigs fed pasteurized milk containing hLZ (P = 0.0478), along with an increase in intraepithelial lymphocytes (P = 0.0255), and decrease in lamina propria thickness in the duodenum (P = 0.0001). Based on these results we conclude that consuming pasteurized milk containing hLZ does not induce an inflammatory response and improves the health of the small intestine in pigs.

Granulated lysozyme as an alternative to antibiotics improves growth performance and small intestinal morphology of 10-day-old pigs1

“…In the current study, pigs consuming lysozyme had villus heights and crypt depths that were similar to those of pigs consuming antibiotics, both of which were improved compared with the villus heights and crypt depths the control group. In contrast, pigs consuming hLZ from goat milk did not show changes in villus height or crypt depth in the ileum or jejunum (Brundige et al, 2008;Cooper et al, 2011). Similar to growth performance measures, this may have been due to decreased lysozyme consumption or the presence of antibiotics in the diets.…”

Consumption of Lysozyme-Rich Milk Can Alter Microbial Fecal Populations

“…After 14 days of HLZ milk consumption, the proportion of Firmicutes in the fecal microbiota was underrepresented and that of Bacteroidetes overrepresented compared to animals consuming control goat milk. The gut surface area of the animals used in this study was investigated previously and was found to be related to an improved absorptive capacity of the intestinal epithelium, as HLZ-fed pigs tended to have longer villi and had a significantly thinner lamina propria in the duodenum (10). A 20% increase in the proportional representation of Bacteroidetes in fecal microbiota in humans has been correlated with a decrease in nutrient absorption (19).…”

“…We have developed transgenic dairy goats that express human lysozyme (HLZ) in their milk at 68% the level normally found in human milk (29) with the goal of incorporating the beneficial protective properties of human milk into readily available livestock milk in order to promote the intestinal and overall health of people of all ages. We previously demonstrated that consumption of milk from HLZ-transgenic goats by animal models results in the modulation of Escherichia coli and total coliform levels in the small intestine as determined using standard culture techniques (30), resistance to intestinal colonization by pathogenic E. coli (5), and histological and cytokine changes coupled with increases in serum metabolite makers indicative of improved gastrointestinal (GI) health (6,10).…”

Analysis of raw goat milk microbiota: Impact of stage of lactation and lysozyme on microbial diversity

“…The milk from hLZ goats has been shown to have a longer shelf-life and in vitro slowed the growth of bacterial isolates responsible for causing the spoilage of milk (Pseudomonas fragi) and mastitis (Escherichia coli and Staphylococcus aureus) but not Lactococcus lactis (Maga et al, 2006b) as the milk can still be used to produce cheese (Scharfen et al, 2007). When consumed by animal models, pasteurized hLZ milk beneficially modulates gut microbiota (Maga et al, 2012), improves gut morphology and circulating metabolites in young pigs (Brundige et al, 2010;Cooper et al, 2011) and helps resolve the symptoms of diarrhea (Cooper et al, 2013), all indicating potential human health benefits. One important question to answer is if lysozyme itself is causing these changes or if byproducts of lysozyme presence in milk (different types of bacteria or metabolites) are influencing the antimicrobial action of the milk.…”