Consumption of transgenic milk containing the antimicrobials lactoferrin and lysozyme separately and in conjunction by 6-week-old pigs improves intestinal and systemic health

Abstract

Lactoferrin and lysozyme are antimicrobial and immunomodulatory proteins produced in high quantities in human milk that aid in gastrointestinal (GI) health and have beneficial effects when supplemented separately and in conjunction in human and animal diets. Ruminants produce low levels of lactoferrin and lysozyme; however, there are genetically engineered cattle and goats that respectively secrete recombinant human lactoferrin (rhLF-milk), and human lysozyme (hLZ-milk) in their milk. Effects of consumption of rhLF-milk, hLZ-milk and a combination of rhLF-and hLZ-milk were tested on young pigs as an animal model for the GI tract of children. Compared with control milk-fed pigs, pigs fed a combination of rhLF and hLZ (rhLF+hLZ) milk had a 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 (MCV) and red blood cells (RBCs) were significantly increased in pigs fed hLZ-milk and rhLF-milk and tended to be increased in rhLF+hLZ-fed pigs, indicating more mature RBCs. These results support previous research demonstrating that pigs fed milk containing rhLF or hLZ had decreased intestinal inflammation, and suggest that in some parameters the combination of lactoferrin and lysozyme have additive effects, in contrast to the synergistic effects reported when utilising in-vitro models.

Lactoferrin suppresses lipopolysaccharide-induced endometritis in mice via down-regulation of the NF-κB pathway

“…A study by Latorre et al demonstrated that LF can bind and sequester LPS, thus preventing activation of the pro-inflammatory pathway, sepsis, and tissue damage [10]. Cooper et al showed that pigs that were fed LF presented decreased intestinal inflammation [11]. Kuhara et al reported that oral ingestion of LF by mice with hepatitis enhanced the expression of IL-11 in the small intestine [12].…”

Production of human lactoferrin and lysozyme in the milk of transgenic dairy animals: past, present, and future

“…However a study has been conducted combining milk from lactoferrin transgenic cows and milk from lysozyme transgenic goats (Cooper et al 2014). Pigs fed a combination of rhLF and hLZ milk had significantly thinner lamina propria layer and significantly deeper crypts.…”

“…As research continues the effects of various milk processing techniques, such as powdering, on the bioactivity of lactoferrin and lysozyme in milk will likely be investigated, since powdering allows for extended shelf life and easier shipment of the milk. Also, it has already been shown that milk containing different concentrations of lactoferrin and lysozyme can induce different physiological changes (Cooper et al 2014), thus more in-depth dose-response studies could be done to determine the threshold concentrations needed to induce specific changes. Additionally investigations into the effects of long term consumption as well as monitoring how long after the cessation of consumption the effects on parameters such as intestinal architecture, immune response, and microbiota persist.…”

“…These results support previous research that shows milk containing rhLF induces proliferation of intestinal crypt cells, and that pigs fed milk containing rhLF and hLZ had decreased intestinal inflammation, particularly in the lamina propria. The increased RBC's shows animals fed these antimicrobials had higher numbers of RBC's and that the RBC's were more mature since as RBC's mature the volume (MCV) decreases (Cooper et al 2014).…”

The Role of Lactoferrin in Gastrointestinal and Immune Development and Function: A Preclinical Perspective

“…[90][91][92] Alternatively, the milk from lactoferrin-transgenic animals has been fed directly to another species (eg, hLF transgenic bovine milk fed to piglets). [93][94][95][96][97] Lactoferrin also has been overexpressed in Chinese hamster ovary, 98 insect cells, 99 yeast, 100 and plant cells, 101 including rice, 102 and these forms also have been shown to be bioactive in vitro 102 and in vivo. 98,100,103,104 However, given the difficulty in dissecting the action of an individual component within the complex milieu of milk, most studies have taken the approach of supplementing a single milk component to a formula.…”