Consumption of milk from transgenic goats expressing human lysozyme in the mammary gland results in the modulation of intestinal microflora

Abstract

Lysozyme is a key antimicrobial component of human milk that has several health-promoting functions including the development of a healthy intestinal tract. However, levels of lysozyme in the milk of dairy animals are negligible. We have generated transgenic dairy goats that express human lysozyme (HLZ) in their milk in an attempt to deliver the benefits of human milk in a continual fashion. To test the feasibility of this transgenic approach to achieve a biological impact at the level of the intestine, feeding trials were conducted in two animal models. Pasteurized milk from HLZ transgenic animals was fed to both kid goats (ruminant model) and young pigs (human model), and the numbers of total coliforms and Escherichia coli present in the small intestine were determined. Data from this proof-of-principle study demonstrate that milk from transgenic animals was capable of modulating the bacterial population of the gut in both animal models. Pigs that consumed pasteurized milk from HLZ transgenic goats had fewer numbers of coliforms and E. coli in their intestine than did those receiving milk from non-transgenic control animals. The opposite effect was seen in goats. Milk from these transgenic animals not only represent one of the first transgenic food products with the potential of benefiting human health, but are also a unique model to study the development and role of intestinal microflora on health, well-being and resistance to disease.

Consumption of Lysozyme-Rich Milk Can Alter Microbial Fecal Populations

“…Using standard culturing techniques, total coliform and E. coli counts in the duodenum and ileum of HLZ-fed pigs tended to be lower than in control-fed pigs, similar to results seen when starting with 14-day-old pigs (5,30). These results indicate the reproducibility of the effect of HLZ milk in differently aged animals at this level of detail.…”

“…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).…”

Endolysins as Antimicrobials

“…Transgenic goat milk containing human lysozyme could protect from mastitis in vitro and showed benefits in animal health for goats drinking the transgenic milk (Maga et al, 2006b;Maga et al, 2006a). Similarly, pigs (Tong et al, 2010) and cattle (Yang et al, 2011) expressing lysozyme in the mammary gland have been created.…”

Role of the Lysozyme Inhibitor Ivy in Growth or Survival ofEscherichia coliandPseudomonas aeruginosaBacteria in Hen Egg White and in Human Saliva and Breast Milk

“…Although lysozyme had no direct antibacterial activity against the tested bacteria in breast milk, this does not exclude an antibacterial effect on other bacteria, for example, gram-positive bacteria. In addition, breast milk lysozyme may modulate the gut microflora, either directly or after being processed by pepsin in the stomach into various antibacterial peptides (8,21,28).…”