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

Published online by Cambridge University Press:  17 December 2013

Caitlin A Cooper ,
Elizabeth A Maga  and
James D Murray
Caitlin A Cooper
Affiliation:
Department of Animal Science, University of California, Davis, USA
Elizabeth A Maga
Affiliation:
Department of Animal Science, University of California, Davis, USA
James D Murray*
Affiliation:
Department of Animal Science, University of California, Davis, USA Department of Population Health and Reproduction, University of California, Davis, USA
*
*For correspondence; e-mail: Jdmurray@ucdavis.edu
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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.

Keywords

Transgeniclactoferrinlysozymemilkhemaetologypigs
Type
Research Article
Information
Journal of Dairy Research , Volume 81 , Issue 1 , February 2014 , pp. 30 - 37
Copyright
Copyright © Proprietors of Journal of Dairy Research 2013 

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References

Actor, JK, Hwang, SA & Kruzel, ML 2009 Lactoferrin as a natural immune modulator. Current Pharmaceutical Design 15 1956–1973 Google Scholar
Brundige, DR, Maga, EA, Klasing, KC & Murray, JD 2008 Lysozyme transgenic goats' milk influences gastrointestinal morphology in young pigs. Journal of Nutrition 138 921–926 Google Scholar
Brundige, DR, Maga, EA, Klasing, KC & Murray, JD 2010 Consumption of pasteurized human lysozyme transgenic goats' milk alters serum metabolite profile in young pigs. Transgenic Research 19 563–574 CrossRefGoogle ScholarPubMed
Cerven, D, DeGeorge, G & Bethell, D 2008 28-day repeated dose oral toxicity of recombinant human holo-lactoferrin in rats. Regulatory Toxicology and Pharmacology 52 174–179 Google Scholar
Cetin, E, Silici, S, Cetin, N & Güçlü, BK 2010 Effects of diets containing different concentrations of propolis on hematological and immunological variables in laying hens. Poultry Science 89 1703–1708 CrossRefGoogle ScholarPubMed
Cooper, CA, Brundige, DR, Reh, WA, Maga, EA & Murray, JD 2011 Lysozyme transgenic goats' milk positively impacts intestinal cytokine expression and morphology. Transgenic Research 20 1235–1243 CrossRefGoogle ScholarPubMed
Cooper, CA, Nelson, KM, Maga, EA & Murray, JD 2013 Consumption of transgenic cows' milk containing human lactoferrin results in beneficial changes in the gastrointestinal tract and systemic health of young pigs. Transgenic Research 22 571–578 CrossRefGoogle ScholarPubMed
Drakesmith, H & Prentice, AM 2012 Hepcidin and the iron-infection axis. Science 338 768–772 Google Scholar
Ellison, RTJ & Giehl, TJ 1991 Killing of Gram-negative bacteria by lactoferrin and lysozyme. Journal of Clinical Investigation 88 1080–1091 Google Scholar
Evans, GO 2009 Animal Hematoxicology: a Practical Guild for Toxicologist and Biomedical Researchers, 1st edition. Boca Raton, FL: Taylor and Francis Group Google Scholar
Fonseca, AM, Pereira, CF, Porto, G & Arosa, FA 2003 Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress. Free Radical Biology and Medicine 35 1404–1416 Google Scholar
Ginsburg, I 2002 Role of lipoteichoic acid in infection and inflammation. Lancet Infectious Disease 2 171–179 Google Scholar
Goldman, AS, Thorpe, LW, Goldblum, RM & Hanson, LA 1986 Anti-inflammatory properties of human milk. Acta Paediatrica Scandinavica 75 689–695 Google Scholar
Harikrishnan, R, Balasundaram, C & Heo, MS 2010 Effect of probiotics enriched diet on Paralichthys olivaceus infected with lymphocystis disease virus (LCDV). Fish and Shellfish Immunology 29 868–874 Google Scholar
Harikrishnan, R, Kim, JS, Kim, MC, Balasundaram, C & Heo, MS 2012 Pomegranate enriched diet enhances the hematology, innate immune response, and disease resistance in olive flounder against Philasterides dicentrarchi. Veterinary Parasitology 187 147–156 Google Scholar
Hettinga, K, van Valenberg, H, de Vries, S, Boeren, S, van Hooijdonk, T, van Arendonk, J & Vervoort, J 2011 The host defense proteome of human and bovine milk. PLoS ONE 6 e19433 Google Scholar
Hu, W, Zhao, J, Wang, J, Yu, T, Wang, J & Li, N 2012 Transgenic milk containing recombinant human lactoferrin modulates the intestinal flora in piglets. Biochemistry and Cell Biology 90 485–496 Google Scholar
Humphrey, BD, Huang, N & Klasing, KC 2002 Rice expressing lactoferrin and lysozyme has antibiotic-like properties when fed to chicks. Journal of Nutrition 132 1214–1218 Google Scholar
Ita, SO, Etim, OE, Ben, EE & Ekpo, OF 2007 Haematopoietic properties of ethanolic extract of Ageratum conyzoides (goat weed) in albino rats. Niger Journal of Physiological Science 22 83–87 Google Scholar
Jacobs, A & Summers, MR 1981 Iron uptake and ferritin synthesis by peripheral blood leucocytes in patients with primary idiopathic haemochromatosis. British Journal of Haematology 49 649–652 Google Scholar
Kruzel, ML, Actor, JK, Boldogh, I & Zimecki, M 2007 Lactoferrin in health and disease. Postepy higieny i medycyny doswiadczalnej 61 261–267 Google Scholar
Kuang, SY, Xiao, WW, Feng, L, Liu, Y, Jiang, J, Jiang, WD, Hu, K, Li, SH, Tang, L & Zhou, XQ 2012 Effects of graded levels of dietary methionine hydroxy analogue on immune response and antioxidant status of immune organs in juvenile Jian carp (Cyprinus carpio var. Jian). Fish and Shellfish Immunology 32 629–636 CrossRefGoogle ScholarPubMed
Kurasawa, T, Takada, K, Ohno, N & Yadomae, T 1996 Effects of murine lysozyme on lipopolysaccharide-induced biological activities. Federation of European Microbiological Societies: Immunology and Medical Microbiology 13 293–301 Google Scholar
Lee, M, Kovacs-Nolan, J, Yang, C, Archibold, T, Fan, MZ & Mine, Y 2009 Hen egg lysozyme attenuates inflammation and modulates local gene expression in a porcine model of dextran sodium sulfate (DSS)-induced colitus. Journal of Agricultural Food Chemistry 57 2233–2240 CrossRefGoogle Scholar
Leitch, EC & Wilcox, MD 1999 Elucidation of the antistaphylococcal action of lactoferrin and lysozyme. Journal of Medical Microbiology 48 867–871 Google Scholar
Liao, Y, Lopez, V, Shafizadeh, TB, Halsted, CH & Lonnerdal, B 2007 Cloning of a pig homologue of the human lactoferrin receptor: expression and localization during intestinal maturation in piglets. Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology 148 584–590 Google Scholar
Liao, Y, Jiang, R & Lonnerdal, B 2012 Biochemical and molecular impacts of lactoferrin on small intestinal growth and development during early life. Biochemistry and Cell Biology 90 476–484 CrossRefGoogle ScholarPubMed
Liu, D, Guo, Y, Wang, Z & Yuan, J 2010 Exogenous lysozyme influences Clostridium perfringens colonization and intestinal barrier function in broiler chickens. Avian Pathology 39 17–24 Google Scholar
Ljungh, A & Wadström, T 2006 Lactic acid bacteria as probiotics. Current Issues in Intestinal Microbiology 7 73–89 Google Scholar
Maga, EA, Shoemaker, CF, Rowe, JD, Bondurant, RH, Anderson, GB & Murray, JD 2006a Production and processing of milk from transgenic goats expressing human lysozyme in the mammary gland. Journal of Dairy Science 89 518–524 Google Scholar
Maga, EA, Cullor, JS, Smith, W, Anderson, GB & Murray, JD 2006b Human lysozyme expressed in the mammary gland of transgenic dairy goats can inhibit the growth of bacteria that cause mastitis and the cold-spoilage of milk. Foodborne Pathology and Disease 3 384–392 Google Scholar
Maga, EA, Walker, RL, Anderson, GB & Murray, JD 2006c Consumption of milk from transgenic goats expressing human lysozyme in the mammary gland results in the modulation of intestinal microflora. Transgenic Research 15 515–519 Google Scholar
Maga, EA, Desai, PT, Weimer, BC, Dao, N, Kültz, D & Murray, JD 2012 Consumption of lysozyme-rich milk can alter microbial fecal populations. Applied and Environmental Microbiology 78 6153–6160 Google Scholar
Mahmoud, KZ & Edens, FW 2012 Breeder age affects small intestine development of broiler chicks with immediate or delayed access to feed. British Poultry Science 53 32–41 CrossRefGoogle ScholarPubMed
Moore, G, Knight, G & Blann, A 2010 Fundamentals of Biomedical Science: Haematology. New York, NY: Oxford University Press Google Scholar
Moriguchi, R, Otaki, Y, Hazeki, S, Shimada, T, Matsumoto, A, Kakita, N, Kaibe, S, Kuragano, T, Nonoguchi, H, Masayoshi, N, Hasuike, Y & Nakanishi, T 2012 High levels of tumor necrosis factor-α downregulate antimicrobial iron transport protein, Nramp1, in chronic hemodialysis patients: a key factor for infection risk. American Journal of Nephrology 35 372–378 Google Scholar
Mountzouris, KC, McCartney, AL & Gibson, GR 2002 Intestinal microflora of human infants and current trends for its nutritional modulation. British Journal of Nutrition 87 405–420 Google Scholar
Newburg, DS & Walker, WA 2007 Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatric Research 61 2–8 Google Scholar
Nielsen, SM, Hansen, GH & Danielsen, EM 2010 Lactoferrin targets T cells in the small intestine. Journal of Gastroenterology 45 1121–1128 Google Scholar
Ohno, N & Morrison, DC 1989a Lipopolysaccharide interaction with lysozyme. Binding of lipopolysaccharide to lysozyme and inhibition of lysozyme enzymatic activity. Journal of Biological Chemistry 264 4434–4441 Google Scholar
Ohno, N & Morrison, DC 1989b Lipopolysaccharide interactions with lysozyme differentially affect lipopolysaccharide immunostimulatory activity. European Journal of Biochemistry 186 629–636 Google Scholar
Pfaffl, MW, Horgan, GW & Dempfle, L 2002 Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Research 30 36 Google Scholar
Scharfen, EC, Mills, DA & Maga, EA 2007 Use of human lysozyme transgenic goat milk in cheese making: effects on lactic acid bacteria performance. Journal of Dairy Science 90 4084–4091 Google Scholar
Takada, K, Ohno, N & Yadomae, T 1994a Binding of lysozyme to lipopolysaccharide suppresses tumor necrosis factor production in vivo. Infection and Immunity 62 1171–1175 Google Scholar
Takada, K, Ohno, N & Yadomae, T 1994b Detoxification of lipopolysaccharide (LPS) by egg white lysozyme. Federation of European Microbiological Societies: Immunology and Medical Microbiology 9 255–263 Google Scholar
Thomassen, EA, van Veen, HA, van Berkel, PH, Nuijens, JH & Abrahams, JP 2005 The protein structure of recombinant human lactoferrin produced in the milk of transgenic cows closely matches the structure of human milk-derived lactoferrin. Transgenic Research 14 397–405 Google Scholar
van Berkel, PH, Welling, MM, Geerts, M, van Veen, HA, Ravensbergen, B, Salaheddine, M, Pauwels, EK, Pieper, F, Nuijens, JH & Nibbering, PH 2002 Large scale production of recombinant human lactoferrin in the milk of transgenic cows. Nature Biotechnology 20 484–487 Google Scholar
van der Linden, DS, Short, D, Dittmann, A & Yu, PL 2009 Synergistic effects of ovine-derived cathelicidins and other antimicrobials against Escherichia coli O157:H7 and Staphylococcus aureus 1056 MRSA. Biotechnology Letters 31 1265–1267 Google Scholar
Wang, L, Trebicka, E, Fu, Y, Ellenbogen, S, Hong, CC, Babitt, JL, Lin, HY & Cherayil, BJ 2012 The bone morphogenetic protein-hepcidin axis as a therapeutic target in inflammatory bowel disease. Inflammatory Bowel Disease 18 112–119 Google Scholar
Wu, X, Yung, LM, Cheng, WH, Yu, PB, Babitt, JL, Lin, HY & Xia, Y 2012 Hepcidin regulation by BMP signaling in macrophages is lipopolysaccharide dependent. PLoS ONE 7 e44622 Google Scholar
Yang, B, Wang, J, Tang, B, Liu, Y, Guo, C, Yang, P, Yu, T, Li, R, Zhao, J, Zhang, L, Dai, Y & Li, N 2011 Characterization of bioactive recombinant human lysozyme expressed in milk of cloned transgenic cattle. PLoS ONE 16 e17593 Google Scholar
Yen, CC, Lin, CY, Chong, KY, Tsai, TC, Shen, CJ, Lin, MF, Su, CY, Chen, HL & Chen, CM 2009 Lactoferrin as a natural regimen for selective decontamination of the digestive tract: recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonates from pathogenic challenge in the gastrointestinal tract. Journal of Infectious Disease 199 590–598 Google Scholar
Zhang, P, Sawicki, V, Lewis, A, Hanson, L, Nuijens, JH & Neville, MC 2001 Human lactoferrin in the milk of transgenic mice increases intestinal growth in ten-day-old suckling neonates. Advances in Experimental Medicine and Biology 501 107–113 Google Scholar