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http://dx.doi.org/10.5713/ajas.15.0120

Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives - A Review  

Melo, A.D.B. (School of Agricultural Sciences and Veterinary Medicine, Pontificia Universidade Catolica do Parana)
Silveira, H. (Department of Animal Sciences, Universidade Federal de Lavras)
Luciano, F.B. (School of Agricultural Sciences and Veterinary Medicine, Pontificia Universidade Catolica do Parana)
Andrade, C. (School of Agricultural Sciences and Veterinary Medicine, Pontificia Universidade Catolica do Parana)
Costa, L.B. (School of Agricultural Sciences and Veterinary Medicine, Pontificia Universidade Catolica do Parana)
Rostagno, M.H. (Department of Animal Sciences, Purdue University)
Publication Information
Asian-Australasian Journal of Animal Sciences / v.29, no.1, 2016 , pp. 16-22 More about this Journal
Abstract
The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.
Keywords
Feed Additives; Intestinal Alkaline Phosphatase; Intestinal Inflammation; Gut Health; Swine;
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1 Brun, L. R., M. L. Brance, M. Lombarte, M. Lupo, V. E. Di Loreto, and A. Rigalli. 2014. Regulation of intestinal calcium absorption by luminal calcium content: role of intestinal alkaline phosphatase. Mol. Nutr. Food. Res. 58:1546-1551.   DOI
2 Burkey, T. E., K. A. Skjolaas, and J. E. Minton. 2009. Board-invited review: porcine mucosal immunity of the gastrointestinal tract. J. Anim. Sci. 87:1493-1501.   DOI
3 Cario, E. 2005. Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2. Gut. 54:1182-1193.   DOI
4 Chen, K. T., M. S. Malo, A. K. Moss, S. Zeller, P. Johnson, F. Ebrahimi, G. Mostafa, S. N. Alam, S. Ramasamy, H. S. Warren, E. L. Hohmann, and R. A. Hodin. 2010. Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase. Am. J. Physiol. Gastrointest. Liver Physiol. 299:G467-G475.   DOI
5 Chen, K. T., M. S. Malo, L. K. Beasley-Topliffe, K. Poelstra, J. L. Millan, G. Mostafa, S. N. Alam, S. Ramasamy, H. S. Warren, E. L. Hohmann, and R. A. Hodin. 2011. A role for intestinal alkaline phosphatase in the maintenance of local gut immunity. Dig. Dis. Sci. 56:1020-1027.   DOI
6 de Lange, C. F. M., J. Pluske, J. Gong, and C. M. Nyachoti. 2010. Strategic use of feed ingredients and feed additives to stimulate gut health and development in young pigs. Livest. Sci. 134:124-134.   DOI
7 Eisenhut, M. 2006. Changes in ion transport in inflammatory disease. J. Inflamm (Lond). 3:5.   DOI
8 Fairbrother, J. M., E. Nadeau, and C. L. Gyles. 2005. Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies. Anim. Health Res. Rev. 6:17-39.   DOI
9 Gallois, M. and I. P. Oswald. 2008. Immunomodulators as efficient alternatives to in-feed antimicrobials in pig production. Arch. Zootech. 11:15-32.
10 Gao, M., N. London, K. Cheng, R. Tamura, J. Jin, O. Schueler-Furman, and H. Yin. 2014. Rationally designed macrocyclic peptides as synergistic agonists of LPS-induced inflammatory response. Tetrahedron. 70:7664-7668.   DOI
11 Goldberg, R. F., W. G. Austen, Jr., X. Zhang, G. Munene, G. Mostafa, S. Biswas, M. McCormack, K. R. Eberlin, J. T. Nguyen, H. S. Tatlidede, H. S. Warren, S. Narisawa, J. L. Millán, and R. A. Hodin. 2008. Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc. Natl. Acad. Sci. USA 105:3551-3556.   DOI
12 Goldstein, D. J., C. Rogers, and H. Harris. 1982. A search for trace expression of placental-like alkaline phosphatase in non-malignant human tissues: demonstration of its occurrence in lung, cervix, testis and thymus. Clin. Chim. Acta. 125:63-75.   DOI
13 Heo, J. M., F. O. Opapeju, J. R. Pluske, J. C. Kim, D. J. Hampson, and C. M. Nyachoti. 2013. Gastrointestinal health and function in weaned pigs: a review of feeding strategies to control postweaning diarrhoea without using in-feed antimicrobial compounds. J. Anim. Physiol. Anim. Nutr (Berl). 97:207-237.   DOI
14 Howe, L. M. 2000. Novel agents in the therapy of endotoxic shock. Expert. Opin. Investig. Drugs. 9:1363-1372.   DOI
15 Hu, C. H., K. Xiao, J. Song, and Z. S. Luan. 2013. Effects of zinc oxide supported on zeolite on growth performance, intestinal microflora and permeability, and cytokines expression of weaned pigs. Anim. Feed. Sci. Technol. 181:65-71.   DOI
16 Lackeyram, D., C. Yang, T. Archbold, K. C. Swanson, and M. Z. Fan. 2010. Early weaning reduces small intestinal alkaline phosphatase expression in pigs. J. Nutr. 140:461-468.   DOI
17 Jang, I. S., Y. H. Ko, S. Y. Kang, and C. Y. Lee. 2007. Effect of a commercial essential oil on growth performance, digestive enzyme activity and intestinal microflora population in broiler chickens. Anim. Feed. Sci. Technol. 134:304-315.   DOI
18 Kim, J. C., C. F. Hansen, B. P. Mullan, and J. R. Pluske. 2012. Nutrition and pathology of weaner pigs: Nutritional strategies to support barrier function in the gastrointestinal tract. Anim. Feed. Sci. Technol. 173:3-16.   DOI
19 Koyama, I., T. Matsunaga, T. Harada, S. Hokari, and T. Komoda. 2002. Alkaline phosphatases reduce toxicity of lipopolysaccharides in vivo and in vitro through dephosphorylation. Clin. Biochem. 35:455-461.   DOI
20 Lalles, J. P. 2010. Intestinal alkaline phosphatase: Multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr. Rev. 68:323-332.   DOI
21 Lalles, J. P. 2014. Intestinal alkaline phosphatase: Novel functions and protective effects. Nutr. Rev. 72:82-94.   DOI
22 Levkut, M., A. Marcin, V. Revajova, L. Lenhardt, I. Danielovic, J. Hecl, J. Blanár, M. Levkutova, and J. Pistl. 2011. Influence of oregano extract on the intestine, some plasma parameters and growth performance in chickens. Acta. Vet. Brno. 61:215-225.   DOI
23 Levkut, M., A. L. Marcin, L. Lenhardt, P. Porvaz, V. Revajova, B. Soltysova, J. Blanar, Z. Sevcikova, and J. Pistl. 2010. Effect of sage extract on alkaline phosphatase, enterocyte proliferative activity and growth performance in chickens. Acta. Vet. Brno. 79:177-183.   DOI
24 Martin, L., R. Pieper, N. Schunter, W. Vahjen, and J. Zentek. 2013. Performance, organ zinc concentration, jejunal brush border membrane enzyme activities and mRNA expression in piglets fed with different levels of dietary zinc. Arch. Anim. Nutr. 67:248-261.   DOI
25 Li, X., J. Yin, D. Li, X. Chen, J. Zang, and X. Zhou. 2006. 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.   DOI
26 Malo, M. S., O. Moaven, N. Muhammad, B. Biswas, S. N. Alam, K. P. Economopoulos, S. S. Gul, S. R. Hamarneh, N. S. Malo, A. Teshager, M. M. Mohamed, Q. Tao, S. Narisawa, J. L. Millan, E. L. Hohmann, H. S. Warren, S. C. Robson, and R. A. Hodin. 2014. Intestinal alkaline phosphatase promotes gut bacterial growth by reducing the concentration of luminal nucleotide triphosphates. Am. J. Physiol. Gastrointest. Liver. Physiol. 306:G826-G838.   DOI
27 Malo, M. S., S. Biswas, M. A. Abedrapo, L. Yeh, A. Chen, and R. A. Hodin. 2006. The pro-inflammatory cytokines, IL-1beta and TNF-alpha, inhibit intestinal alkaline phosphatase gene expression. DNA. Cell. Biol. 25:684-695.   DOI
28 Martinez-Moya, P., M. Ortega-Gonzalez, R. Gonzalez, A. Anzola, B. Ocon, C. Hernandez-Chirlaque, R. Lopez-Posadas, M. D. Suarez, A. Zarzuelo, O. Martinez-Augustin, and F. Sanchez de Medina. 2012. Exogenous alkaline phosphatase treatment complements endogenous enzyme protection in colonic inflammation and reduces bacterial translocation in rats. Pharmacol. Res. 66:144-153.   DOI
29 McGhee, J. R., M. E. Lamm, and W. Strober. 1999. Mucosal immune responses: an overview. In: Mucosal Immunology, 2nd Ed. (Eds. P. L. Ogra, J. Mestecky, and M. E. Lamm). Academic Press, San Diego, CA, USA. pp. 485-506.
30 Moss, A. K., S. R. Hamarneh, M. M. Mohamed, S. Ramasamy, H. Yammine, P. Patel, K. Kaliannan, S. N. Alam, N. Muhammad, O. Moaven, A. Teshager, N. S. Malo, S. Narisawa, J. L. Millán, H. S. Warren, E. Hohmann, M. S. Malo, and R. A. Hodin. 2013. Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate. Am. J. Physiol. Gastrointest. Liver. Physiol. 304:G597-604.   DOI
31 Mussa, T., M. Ballester, E. Silva-Campa, M. Baratelli, N. Busquets, M. P. Lecours, J. Dominguez, M. Amadori, L. Fraile, J. Hernandez, and M. Montoya. 2013. Swine, human or avian influenza viruses differentially activates porcine dendritic cells cytokine profile. Vet. Immunol. Immunopathol. 154:25-35.   DOI
32 Oshiumi, H., M. Matsumoto, K. Funami, T. Akazawa, and T. Seya. 2003. TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat. Immunol. 4:161-167.   DOI
33 Perez, R., F. Stevenson, J. Johnson, M. Morgan, K. Erickson, N. E. Hubbard, L. Morand, S. Rudich, S. Katznelson, and J. B. German. 1998. Sodium butyrate upregulates Kupffer cell PGE2 production and modulates immune function. J. Surg. Res. 78:1-6.   DOI
34 Pie, S., J. P. Lalles, F. Blazy, J. Laffitte, B. Seve, and I. P. Oswald. 2004. Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. J. Nutr. 134:641-647.   DOI
35 Poelstra, K., W. W. Bakker, P. A. Klok, J. A. Kamps, M. J. Hardonk, and D. K. Meijer. 1997a. Dephosphorylation of endotoxin by alkaline phosphatase in vivo. Am. J. Pathol. 151:1163-1169.
36 Poelstra, K., W. W. Bakker, P. A. Klok, M. J. Hardonk, and D. K. Meijer. 1997b. A physiologic function for alkaline phosphatase: endotoxin detoxification. Lab. Invest. 76:319-327.
37 Shelton, N. W., M. D. Tokach, J. L. Nelssen, R. D. Goodband, S. S. Dritz, J. M. DeRouchey, and G. M. Hill. 2011. Effects of copper sulfate, tri-basic copper chloride, and zinc oxide on weanling pig performance. J. Anim. Sci. 89:2440-2451.   DOI
38 Prakash, U. N. and K. Srinivasan. 2010. Beneficial influence of dietary spices on the ultrastructure and fluidity of the intestinal brush border in rats. Br. J. Nutr. 104:31-39.   DOI
39 Roselli, M., A. Finamore, I. Garaguso, M. S. Britti, and E. Mengheri. 2003. Zinc oxide protects cultured enterocytes from the damage induced by Escherichia coli. J. Nutr. 133:4077-4082.   DOI
40 Sang, Y., J. Yang, C. R. Ross, R. R. Rowland, and F. Blecha. 2008. Molecular identification and functional expression of porcine Toll-like receptor (TLR) 3 and TLR7. Vet. Immunol. Immunopathol. 125:162-167.   DOI
41 Shimosato, T., M. Tohno, H. Kitazawa, S. Katoh, K. Watanabe, Y. Kawai, H. Aso, T. Yamaguchi, and T. Saito. 2005. Toll-like receptor 9 is expressed on follicle-associated epithelia containing M cells in swine Peyer's patches. Immunol. Lett. 98:83-89.   DOI
42 Shinkai, H., M. Tanaka, T. Morozumi, T. Eguchi-Ogawa, N. Okumura, Y. Muneta, T. Awata, and H. Uenishi. 2006a. Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes. Immunogenetics 58:324-330.   DOI
43 Shinkai, H., Y. Muneta, K. Suzuki, T. Eguchi-Ogawa, T. Awata, and H. Uenishi. 2006b. Porcine Toll-like receptor 1, 6, and 10 genes: complete sequencing of genomic region and expression analysis. Mol. Immunol. 43:1474-1480.   DOI
44 Taras, D., W. Vahjen, M. Macha, and O. Simon. 2006. Performance, diarrhea incidence, and occurrence of Escherichia coli virulence genes during long-term administration of a probiotic Enterococcus faecium strain to sows and piglets. J. Anim. Sci. 84:608-617.   DOI
45 Smith, F., J. E. Clark, B. L. Overman, C. C. Tozel, J. H. Huang, J. E. Rivier, A. T. Blikslager, and A. J. Moeser. 2010. Early weaning stress impairs development of mucosal barrier function in the porcine intestine. Am. J. Physiol. Gastrointest. Liver. Physiol. 298:G352-G363.   DOI
46 Sussman, N. L., R. Eliakim, D. Rubin, D. H. Perlmutter, K. DeSchryver-Kecskemeti, and D. H. Alpers. 1989. Intestinal alkaline phosphatase is secreted bidirectionally from villous enterocytes. Am. J. Physiol. 257(1 Pt 1):G14-G23.
47 Takeda, K., and S. Akira. 2004. TLR signaling pathways. Semin. Immunol. 16:3-9.   DOI
48 Tohno, M., T. Shimosato, H. Kitazawa, S. Katoh, I. D. Iliev, T. Kimura, Y. Kawai, K. Watanabe, H. Aso, T. Yamaguchi, and T. Saito. 2005. Toll-like receptor 2 is expressed on the intestinal M cells in swine. Biochem. Biophys. Res. Commun. 330:547-554.   DOI
49 Tohno, M., T. Shimosato, M. Moue, H. Aso, K. Watanabe, Y. Kawai, T. Yamaguchi, T. Saito, and H. Kitazawa. 2006. Toll-like receptor 2 and 9 are expressed and functional in gutassociated lymphoid tissues of presuckling newborn swine. Vet. Res. 37:791-812.   DOI
50 Tucci, F. M., M. C. Thomaz, L. S. O. Nakaghi, M. I. Hannas, A. J. Scandolera, and F. E. L. Budino. 2011. The effect of the addition of trofic agents in weaned piglet diets over the structure and ultra-structure of small intestine and over performance. Arq. Bras. Med. Vet. Zootec. 63:931-940.   DOI
51 Vaishnava, S. and L. V. Hooper. 2007. Alkaline phosphatase: keeping the peace at the gut epithelial surface. Cell. Host. Microbe. 2:365-367.   DOI
52 Tuin, A., A. Huizinga-Van der Vlag, A. M. van Loenen-Weemaes, D. K. Meijer, and K. Poelstra. 2006. On the role and fate of LPS-dephosphorylating activity in the rat liver. Am. J. Physiol. Gastrointest. Liver. Physiol. 290:G377-G385.   DOI
53 Uenishi, H. and H. Shinkai. 2009. Porcine Toll-like receptors: the front line of pathogen monitoring and possible implications for disease resistance. Dev. Comp. Immunol. 33:353-361.   DOI
54 Uysal, G., A. Sökmen, and S. Vidinlisan. 2000. Clinical risk factors for fatal diarrhea in hospitalized children. Indian. J. Pediatr. 67:329-333.   DOI
55 van Veen, S. Q., A. K. van Vliet, M. Wulferink, R. Brands, M. A. Boermeester, and T. M. van Gulik. 2005. Bovine intestinal alkaline phosphatase attenuates the inflammatory response in secondary peritonitis in mice. Infect. Immun. 73:4309-4314.   DOI
56 Weber, T. E. and B. J. Kerr. 2008. Effect of sodium butyrate on growth performance and response to lipopolysaccharide in weanling pigs. J. Anim. Sci. 86:442-450.   DOI
57 Yamamoto, M., S. Sato, K. Mori, K. Hoshino, O. Takeuchi, K. Takeda, and S. Akira. 2002. Cutting edge: A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J. Immunol. 169:6668-6672.   DOI
58 Zhang, L., J. Liu, J. Bai, X. Wang, Y. Li, and P. Jiang. 2013. Comparative expression of Toll-like receptors and inflammatory cytokines in pigs infected with different virulent porcine reproductive and respiratory syndrome virus isolates. Virol. J. 10:135.   DOI
59 Akira, S., K. Takeda, and T. Kaisho. 2001. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat. Immunol. 2:675-680.   DOI
60 Abasht, B., M. G. Kaiser, and S. J. Lamont. 2008. Toll-like receptor gene expression in cecum and spleen of advanced intercross line chicks infected with Salmonella enterica serovar Enteritidis. Vet. Immunol. Immunopathol. 123:314-323.   DOI
61 Alam, S. N., H. Yammine, O. Moaven, R. Ahmed, A. K. Moss, B. Biswas, N. Muhammad, R. Biswas, A. Raychowdhury, K. Kaliannan, S. Ghosh, M. Ray, S. R. Hamarneh, S. Barua, N. S. Malo, A. K. Bhan, M. S. Malo, and R. A. Hodin. 2014. Intestinal alkaline phosphatase prevents antibiotic-induced susceptibility to enteric pathogens. Ann. Surg. 259:715-722.   DOI
62 Artis, D. 2008. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat. Rev. Immunol. 8:411-420.   DOI
63 Berkes, J., V. K. Viswanathan, S. D. Savkovic, and G. Hecht. 2003. Intestinal epithelial responses to enteric pathogens: Effects on the tight junction barrier, ion transport, and inflammation. Gut. 52:439-451.   DOI
64 Bates, J. M., J. Akerlund, E. Mittge, and K. Guillemin. 2007. Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell. Host. Microbe. 2:371-382.   DOI
65 Bederska-Łojewska, D. and M. Pieszka. 2011. Modulating gastrointestinal microflora of pigs through nutrition using feed additives. Ann. Anim. Sci. 11:333-355.
66 Bentala, H., W. R. Verweij, A. Huizinga-Van der Vlag, A. M. van Loenen-Weemaes, D. K. Meijer, and K. Poelstra. 2002. Removal of phosphate from lipid A as a strategy to detoxify lipopolysaccharide. Shock. 18:561-566.   DOI
67 Beumer, C., M. Wulferink, W. Raaben, D. Fiechter, R. Brands, and W. Seinen. 2003. Calf intestinal alkaline phosphatase, a novel therapeutic drug for lipopolysaccharide (LPS)-mediated diseases, attenuates LPS toxicity in mice and piglets. J. Pharmacol. Exp. Ther. 307:737-744.   DOI
68 Beutler, B. and E. T. Rietschel. 2003. Innate immune sensing and its roots: the story of endotoxin. Nat. Rev. Immunol. 3:169-176.   DOI
69 Bevins, C. L., E. Martin-Porter, and T. Ganz. 1999. Defensins and innate host defence of the gastrointestinal tract. Gut. 45:911-915.   DOI
70 Bol-Schoenmakers, M., D. Fiechter, W. Raaben, I. Hassing, R. Bleumink, D. Kruijswijk, K. Maijoor, M. Tersteeg-Zijderveld, R. Brands, and R. Pieters. 2010. Intestinal alkaline phosphatase contributes to the reduction of severe intestinal epithelial damage. Eur. J. Pharmacol. 633:71-77.   DOI