Modern commercial pig farming systems inflict increased stress in animals, which often leads to various negative changes in the gastro-intestinal tract, especially in the case of piglets. Ban of antibiotics, used as growth promoters, has caused a need for alternatives to conventional antimicrobials in swine diets. Use of pre-/or probiotics, organic acids and plant extracts is often recommended, but it seems that zinc oxide and cooper salts, which were traditionally included in high doses to piglets diet, possess the highest efficacy. In commercial conditions feeding piglets with high doses of Zn and/or Cu stimulates piglets daily gain and decreases feed conversion factor. However, as heavy metals Zn and Cu tend to accumulate in soil and cause serious environmental pollution of soil and tap-water. Furthermore, high zinc concentrations (2500÷3000 mg/kg feed) in feed may have an impact on development of antimicrobial resistance, and may regulate the expression of genes that modify piglets’ immune response. Therefore, the use of high doses of ZnO and/or Cu salts, as growth promoter, has always been a subject of discussion, and caused different legal status of such treatment in various EU countries. This short review describes current European Food Safety Authority (EFSA) point of view on the use of ZnO in medicated feed. The higher bioavailability of recently introduced new sources or forms of these metals allows for substantial reduction of dietary inclusion rate, which should have a positive outcome for pigs health and the environment.
Agga GE, Scott HM, Vinasco J, Nagaraja TG, Amachawadi RG, Bai J, Norby B, Renter DG, Dritz SS, Nelssen JL, Tokach MD (2015) Effects of chlortetracycline and copper supplementation on the prevalence, distribution, and quantity of antimicrobial resistance gens in the fecal metagenome of weaned pigs. Prev Vet Med 119: 179-189.
Ahmed ST, Hwang JA, Hoon J, Mun HS, Yang CJ (2014) Comparison of single and blend acidifiers as alternative to antibiotics on growth performance, fecal microflora, and humoral immunity in weaned piglets. Asian-Australas J Anim Sci 27: 93-100.
Ansari MA, Khan HM, Khan AA, Sultan A, Azam A (2012) Characterization of clinical strains of MSSA, MRSA and MRSE isolated from skin and soft tissue infections and the antibacterial activity of ZnO nanoparticles. World J Microbiol Biotechnol 28: 1605-1613.
Armstrong TA, Cook DR, Ward MM, Williams CM, Spears JW (2004) Effect of dietary copper source (cupric citrate and cupric sulfate) and concentration on growth performance and fetal copper excretion in weanling pigs. J Anim Sci 82: 1234-1240.
Bednorz C, Oelgeschlager K, Kinnemann B, Hartmann S, Neumann K, Pieper R, Bethe A, Semmler T, Tedin K, Schierack P, Wieler LH, Guenther S (2013) The broader context of antibiotic resistance: zinc feed supplementation of piglets increases the proportion of multi-resistant Escherichia coli in vivo. Int J Med Microbiol 303: 396-403.
Brugger D, Windisch WM (2015) Environmental responsibilities of livestock feeding using trace mineral supplements. Anim Nutr 1: 113-118.
Castillo M, Martin-Orue SM, Taylor-Pickard JA, Perez JF, Gasa J (2008) Use of mannanoligosaccharides and zinc chelate as growth promoters and diarrhea preventive in weaning pigs: Effects on microbiota and gut function. J Anim Sci 86: 94-101.
Carlson D, Poulsen DH, Sehested J (2004) Influence of weaning and effect of post weaning dietary zinc and copper on electrophysiological response to glucose, theophylline and 5-HT in piglet small intestinal mucosa. Comp Biochem Physiol A 137: 757-765.
Castro M (2005) Use of additives on the feeding of monogastric animals. Cuban J Anim Sci 39: 439.
Cho JH, Zhao PY, Kim IH (2011) Probiotics as a dietary additive for pigs: a review. J Anim Vet Advances 10: 2127-2134.
Cho JH, Upadhaya SD, Kim IH (2015) Effects of dietary supplementation of modified zinc oxide on growth performance, nutrient digestibility, blood profiles, fecal microbials shedding and fecal score in weanling pigs. Anim Sci J 86: 617-623.
Cromwell GL (1997) Copper as a nutrient for animals. In: Richardson HW (ed) Handbook of Copper Compounds and Applications. Marcel Dekker Inc., New York, pp 177-202.
Cromwell GL, Lindenmann MD, Monegue HJ, Hall DD, Orr DE (1998) Tribasic copper chloride and copper sulfate as copper sources for weanling pigs. J Anim Sci 76: 118-123.
Davin R, Manzanilla EG, Klasing KC, Perez JF (2012) Evolution of zinc, iron, and copper concentrations along the gastrointestinal tract of piglets weaned with or without in-feed high doses of zinc oxide compared to unweaned littermates. J Anim Sci 90: (Suppl 4): 248-250.
Davin R, Manzanilla EG, Klasing KC, Perez JF (2013) Effect of weaning and in-feed high doses of zinc oxide on zinc levels in different body compartments of piglets. J Anim Physiol Anim Nutr 97, (Suppl. s1): 6-12.
Demir E, Akca H, Kaya B, Burgucu D, Tokgun O, Turna F, Aksakal S, Vales G, Creus A, Marcos R (2014) Zinc oxide nanoparticles: genotoxicity, interaction with UV-light and cell-transforming potential. J Hazard Mater 264: 420-429.
EFSA (2014) Scientific opinion on the potential reduction of currently authorized maximum zinc content in complete feed. EFSA J 12: 3668. www.efsa.europa.eu/efsajournal
Grela ER, Pastuszak J (2004) Nutritional and prophylactic importance of zinc in pigs production. Med Weter 60: 1254-1258.
Hahn TW, Lohakare JD, Lee SL, Moon WK, Chae BJ (2006) Effects of supplementation of beta-glucans on growth performance, nutrient digestibility, and immunity in weaning pigs. J Anim Sci 84: 1422-1428.
Hernandez A, Pluske JR, D’Souza DN, Mullan BP (2008) Levels of copper and zinc in diets for growing and finishing pigs can be reduced without detrimental effects on production and mineral status. Animal 2: 1763-1771.
Heo JM, Opapeju FO, Pluske JR, Kim JC, Hampson DJ, Nyachoti CM (2013) Gastrointestinal health and function in weaning pigs: a review of feeding strategies to control post-weaning diarrhoea without using in-feed antimicrobial compounds. J Anim Physiol Anim Nutr (Berl) 97: 207-237.
Hill GM, Ku PK, Miller ER, Ullrey DE, Losty TA, O’Dell BL (1983) A copper deficiency in neonatal pigs induced by a high zinc maternal diet. J Nutr 113: 867-872.
Hojberg O, Canibe N, Poulsen HD, Hedemann MS, Jensen BB (2005) Influence of dietary zinc oxide and copper sulfate on the gastrointestinal ecosystem in newly weaned piglets. Appl Environ Microbiol 71: 2267-2277.
Holman DB, Chenier MR (2015) Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance. Can J Microbiol 61: 785-798.
Holzel CS, Muller C, Harms KS, Mikolajewski S, Schwaiger K, Bauer J (2012) Heavy metals in liquid pig manure in light of bacterial antimicrobial resistance. Environ Res 113: 21-27.
Jacela JY, DeRouchey JM, Tokach MD, Goodband RD, Nelssen JL, Renter DG, Dritz SS (2010) Feed additives for swine: Fact sheets-high dietary levels of copper and zinc for young pigs, and phytase. J Swine Health Prod 18: 87-92.
Jensen J, Larsen MM, Bak J (2016) National monitoring study in Denmark finds increased and critical levels of copper and zinc in arable soils fertilized with pig slurry. Environ Pollut 214: 334-340.
Jongbloed AW, Bikker P, Thissen JT (2011) Dose-response relationship between dietary copper level and growth performance in piglets and growing -finishing pigs and effect of withdrawal of a high copper level on subsequent growth performance. Report 483, Wageningen UR Livestock Research. http://www.livestockresearch.wur.nl
Kim JC, Hansen CF, Pluske JR, Mullan BP (2010) Evaluating the replacement of zinc oxide with an encapsulated zinc oxide product as a means of controlling post-weaning diarrhea in piglets. Murdoch University, Project 2C-114. http://apri.com.au/2C-114_Final_report
Lampromsuk P, Bunchasak C, Kaewtapee C, Sawanon S, Poeikhampha T (2012) Effect of supplementing acidifiers and organic zinc in diet on growth performances and gut conditions of pigs. J Appl Sci 12: 553-560.
Li J, Li DF, Xing JJ, Cheng ZB, Lai CH (2006) Effects of β-glucan extracted from Saccharomyces cerevisiae on growth performance, and immunological and somatotropic responses of pigs challenged with Escherichia coli lipopolysaccharide. J Anim Sci 84: 2374-2381.
Li X, Yin J, Li D, Chen X, Zang J, Zhou X (2006a) Dietary supplementation with zinc oxide increases Igf-I and Igf-I receptor gene expression in the small intestine of weanling piglets. J Nutr 136: 1786-1791.
Lipinski K, Mazur M, Antoszkiewicz Z, Makowski Z (2014) The effect of dietary supplementation with a herbal product, a bland of organic acids and zinc oxide on nutrient digestibility and growth performance in weaned piglets. Pol J Natur Sc 29: 119-127.
Liu P, Pieper R, Rieger J, Vahjen W, Davin R, Plendl J, Meyer W, Zentek J (2014) Effect of dietary zinc oxide on morphological characteristics, mucin composition and gene expression in the colon of weaned piglets. PloS one 9: e91091.
Malka E, Perelshtein I, Lipovsky Y, Shalom Y, Naparstek L, Perkas N, Patrick T, Lubart R, Nitzan Y, Banin E, Gedanken A (2013) Eradication of multi-drug resistant bacteria by a novel Zn-doped CuO nanocomposite. Small 9: 4069-4076.
Mavromichalis I, Peter CM, Parr TM, Ganessunker D, Baker DH (2000) Growth-promoting efficacy in young pigs of two sources of zinc oxide having either a high or a low bioavailability of zinc. J Anim Sci 78: 2896-2902.
McAlpine P, O’Shea CJ, Varley PF, Flynn B, O’Doherty JV (2012) The effect of seaweed extract as an alternative to zinc oxide diets on growth performance, nutrient digestibility, and fecal score of weaned piglets. J Anim Sci 90: (Suppl 4): 224-226
Missotten JA, Goris J, Jakobsen M, Van Coillie E, Herman L, De Smet S, Dierick NA, Heyndrickx M (2009) Screening of isolated lactic acid bacteria as potential beneficial strains for fermented liquid pig feed production. Anim Feed Sci Technol 150: 122-138.
Morales J, Cordero G, Pineiro C, Durosoy S (2012) Zinc oxide at low supplementation level improves productive performance and health status of piglets. J Anim Sci 90: 436-438.
Moreno MA (2014) Survey of quantitative antimicrobial consumption per production stage in farrow-to-finish pig farms in Spain. Vet Rec Open 1. e000002
Mullan BP, Wilson RH, Harris D, Allen JG, Naylor A (2007) Supplementation of weaning pig diets with zinc oxide or Bioplex TM Zinc. Pig Industry, 1288. en.engormix/pig/supplementation-weaner-pig/141-pO
NRC (National Research Council) (2005) Mineral tolerance of domestic animals. Second revised edition. The National Academies Press, Washington D.C. www.nap.edu.read/11309/chapter/1
Perez VG, Waguespack AM, Bidner TD, Southern LL, Fakler TM, Ward TL, Steidinger M, Pettigrew JE (2011) Additivity of effects from dietary copper and zinc on growth performance and fecal microbiota of pigs after weaning. J Anim Sci 89: 414-425.
Pieper R, Vahjen W, Neumann K, Van Kessel AG, Zentek J (2012) Dose-dependent effects of dietary zinc oxide on bacterial communities and metabolic profiles in the ileum of weaned pigs. J Anim Physiol Anim Nutr (Berl) 96: 825-833.
Regulation No 1831/2003, Regulation of the European Parliament and of the Council. Official Journal of European Union, 2003, L 268/29 eur-lex.europa.edu/legal-content/EN/TXT/?uri
Roof MD, Mahan DC (1982) Effect of carbadox and various dietary copper levels for weanling swine. J Anim Sci 55: 1109-1117.
Sargeant HR, McDowall KJ, Miller HM, Shaw MA (2010) Dietary zinc oxide affects the expression of genes associated with inflammation: Transcriptome analysis in piglets challenged with ETEC K88. Vet Immunol Immunopathol 137: 120-129.
Shelton NW, Tokach MD, Nelssen JL, Goodband RD, Dritz SS, DeRouchey JM, Hill GM (2011) Effects of copper sulfate, tri-basic copper chloride, and zinc oxide on weanling pig performance. J Anim Sci 89: 2440-2451.
Sirelkhatim A, Mahmud S, Seeni A, Kaus NH, Ann LC, Bakhori SK, Hasan H, Mohamad D (2015) Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nano-Micro Letters 7: 219-242.
Slifierz MJ, Friendship R, Weese JS (2014) Zinc Oxide therapy increases prevalence and persistence of methicillin-resistant Staphylococcus in pigs: a randomized controlled trial. Zoonoses Public Health 62: 301-308.
Tayel AA, El-Tras WF, Moussa S, El-Baz AF, Mahrous H, Salem MF, Brimer L (2011) Antibacterial action of zinc oxide nanoparticles against foodborne pathogens. J Food Safety 31: 211-218.
Thacker PA (2013) Alternatives to antibiotics as growth promoters for use in swine production: a review. J Anim Sci Biotechnol 4(35): 1-12.
Thati V, Roy AS, Prasad A, Shivannavar CT, Gaddad SM (2010) Nanostructured zinc oxide enhances the activity of antibiotics against Staphylococcus aureus. J Biosci Tech 1: 64-69.
Turner JL, Dritz SS, Minton JE (2001) Alternatives to conventional antimicrobials in swine diets. Prof Anim Sci 17: 217-226.
Vondruskova H, Slamova R, Trckova M, Zraly, Pavlik I (2010) Alternatives to antibiotic growth promoters in prevention of diarrhoea in weaned piglets: a review. Vet Med 55: 199-224.
Wang Z, Burwinkel M, Chai W, Lange E, Blohm U, Breithaupt A, Hoffmann B, Twardziok S, Rieger J, Janczyk P, Pieper R, Osterrieder N (2014) Dietary Enterococcus faecium NCIMB 10415 and zinc oxide stimulate immune reactions to trivalent influenza vaccination in pigs but do not affect virological response upon challenge infection. Plos one 9: e87007.
Yin J, Li X, LiD, Yue T, Fang Q, Ni J, Zhou X, Wu G (2009) Dietary supplementation with zinc oxide stimulates ghrelin secretion from stomach of young pigs. J Nutr Biochem 20: 783-790.
Zhang B, Guo Y (2009) Supplemental zinc reduced intestinal permeability by enhancing occluding and zonula occludens proteins 1 (ZO-1) expression in weaning piglets. Br J Nutr 102: 687-693.
Zhou W, Kornegay ET, Lindermann MD, Swinkels JW, Welten MK, Wong EA (2014) Stimulation of growth by intravenous injection of copper in weanling pigs. J Anim Sci 72: 2395-2403.