Amino Acids

, Volume 49, Issue 8, pp 1277–1291 | Cite as

Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models

Review Article
Part of the following topical collections:
  1. Cellular, Organoid and Animal Models in Therapeutics

Abstract

Animal models are needed to study and understand a human complex disease. Because of their similarities in anatomy, structure, physiology, and pathophysiology, the pig has proven its usefulness in studying human gastrointestinal diseases, such as inflammatory bowel disease, ischemia/reperfusion injury, diarrhea, and cancer. To understand the pathogenesis of these diseases, a number of experimental models generated in pigs are available, for example, through surgical manipulation, chemical induction, microbial infection, and genetic engineering. Our interests have been using amino acids as therapeutics in pig and human disease models. Amino acids not only play an important role in protein biosynthesis, but also exert significant physiological effects in regulating immunity, anti-oxidation, redox regulation, energy metabolism, signal transduction, and animal behavior. Recent studies in pigs have shown that specific dietary amino acids can improve intestinal integrity and function under normal and pathological conditions that protect the host from different diseases. In this review, we summarize several pig models in intestinal diseases and how amino acids can be used as therapeutics in treating pig and human diseases.

Keywords

Pig models Intestinal disease Amino acids Therapeutics 

Abbreviations

Akt

Protein kinase B

AMPK

AMP-activated protein kinase

APC

Adenomatous polyposis coli

BCAA

Branched-chain amino acids

CRC

Colorectal cancer

CRH

Corticotropin-releasing hormone

DAO

Diamine oxidase

DSS

Dextran sodium sulphate

ERK

Extracellular signal-regulated kinase

FAP

Familial adenomatous polyposis

I/R

Ischemia/reperfusion

IBD

Inflammatory bowel disease

IL

Interleukin

LPS

Lipopolysaccharide

mTOR

Mammalian target of rapamycin

NAC

N-Acetylcysteine

NOD

Nucleotide-binding oligomerization domain protein

OAT

Ornithine-δ-aminotransferase

PI3K

Phosphatidylinositol 3-kinase

P5C

1-Pyrroline-5-carboxylate

ROS

Reactive oxygen species

TLR

Toll-like receptor

TNBS

Trinitrobenzene sulfonic acid

TNF

Tumor necrosis factor

ZO

Zonula occludens

References

  1. Alam NH, Raqib R, Ashraf H, Qadri F, Ahmed S, Zasloff M, Agerberth B, Salam MA, Gyr N, Meier R (2011) l-Isoleucine-supplemented oral rehydration solution in the treatment of acute diarrhoea in children: a randomized controlled trial. J Health Popul Nutr 29:183–190PubMedPubMedCentralGoogle Scholar
  2. Aschenbach JR, Ahrens F, Schwelberger HG, Fürll B, Roesler U, Hensel A, Gäbel G (2007) Functional characteristics of the porcine colonic epithelium following transportation stress and Salmonella infection. Scand J Gastroenterol 42:708–716PubMedCrossRefGoogle Scholar
  3. Baird CH, Niederlechner S, Beck R, Kallweit AR, Wischmeyer PE (2013) l-Threonine induces heat shock protein expression and decreases apoptosis in heat-stressed intestinal epithelial cells. Nutrition 29:1404–1411PubMedPubMedCentralCrossRefGoogle Scholar
  4. Blikslager AT, Rhoads JM, Bristol DG, Roberts MC, Argenzio RA (1999) Glutamine and transforming growth factor-alpha stimulate extracellular regulated kinases and enhance recovery of villous surface area in porcine ischemic-injured intestine. Surgery 125:186–194PubMedCrossRefGoogle Scholar
  5. Bong YS, Assefnia S, Tuohy T, Neklason DW, Burt RW, Ahn J, Jiang HJ, Byers SW (2016) A role for the vitamin D pathway in non-intestinal lesions in genetic and carcinogen models of colorectal cancer and in familial adenomatous polyposis. Oncotarget 7:80508–80520PubMedPubMedCentralGoogle Scholar
  6. Chen Y, Li D, Dai Z, Piao X, Wu Z, Wang B, Zhu Y, Zeng Z (2014) l-Methionine supplementation maintains the integrity and barrier function of the small-intestinal mucosa in post-weaning piglets. Amino Acids 46:1131–1142PubMedCrossRefGoogle Scholar
  7. Chen S, Liu Y, Wang X, Wang H, Li S, Shi H, Zhu H, Zhang J, Pi D, Hu CA, Lin X, Odle J (2016) Asparagine improves intestinal integrity, inhibits TLR4 and NOD signaling, and differently regulates p38 and ERK1/2 signaling in weanling piglets after LPS challenge. Innate Immun 22:577–587PubMedCrossRefGoogle Scholar
  8. Cho WS, Chae C (2004) Expression of cyclooxygenase-2 and nitric oxide synthase 2 in swine ulcerative colitis caused by Salmonella typhimurium. Vet Pathol 41:419–423PubMedCrossRefGoogle Scholar
  9. Clevers H (2004) At the crossroads of inflammation and cancer. Cell 118:671–674PubMedCrossRefGoogle Scholar
  10. Clouard C, Meunier-Salaün MC, Val-Laillet D (2012) Food preferences and aversions in human health and nutrition: how can pigs help the biomedical research? Animal 6:118–136PubMedCrossRefGoogle Scholar
  11. Coëffier M, Claeyssens S, Bensifi M, Lecleire S, Boukhettala N, Maurer B, Donnadieu N, Lavoinne A, Cailleux AF, Déchelotte P (2011) Influence of leucine on protein metabolism, phosphokinase expression, and cell proliferation in human duodenum. Am J Clin Nutr 93:1255–1262PubMedCrossRefGoogle Scholar
  12. Corl BA, Odle J, Niu X, Moeser AJ, Gatlin LA, Phillips OT, Blikslager AT, Rhoads JM (2008) Arginine activates intestinal p70(S6k) and protein synthesis in piglet rotavirus enteritis. J Nutr 138:24–29PubMedGoogle Scholar
  13. Croner RS, Brueckl WM, Reingruber B, Hohenberger W, Guenther K (2005) Age and manifestation related symptoms in familial adenomatous polyposis. BMC Cancer 5:24PubMedPubMedCentralCrossRefGoogle Scholar
  14. Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2012) Regulatory role for l-arginine in the utilization of amino acids by pig small-intestinal bacteria. Amino Acids 43:233–244PubMedCrossRefGoogle Scholar
  15. Dai ZL, Li XL, Xi PB, Zhang J, Wu G, Zhu WY (2013) l-Glutamine regulates amino acid utilization by intestinal bacteria. Amino Acids 45:501–512PubMedCrossRefGoogle Scholar
  16. de Vogel S, Dindore V, van Engeland M, Goldbohm RA, van den Brandt PA, Weijenberg MP (2008) Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 138:2372–2378PubMedCrossRefGoogle Scholar
  17. Effenberger-Neidnicht K, Jägers J, Verhaegh R, de Groot H (2014) Glycine selectively reduces intestinal injury during endotoxemia. J Surg Res 192:592–598PubMedCrossRefGoogle Scholar
  18. Ewaschuk JB, Murdoch GK, Johnson IR, Madsen KL, Field CJ (2011) Glutamine supplementation improves intestinal barrier function in a weaned piglet model of Escherichia coli infection. Br J Nutr 106:870–877PubMedCrossRefGoogle Scholar
  19. Fang Z, Yao K, Zhang X, Zhao S, Sun Z, Tian G, Yu B, Lin Y, Zhu B, Jia G, Zhang K, Chen D, Wu D (2010) Nutrition and health relevant regulation of intestinal sulfur amino acid metabolism. Amino Acids 39:633–640PubMedCrossRefGoogle Scholar
  20. Faure M, Mettraux C, Moennoz D, Godin JP, Vuichoud J, Rochat F, Breuillé D, Obled C, Corthésy-Theulaz I (2006) Specific amino acids increase mucin synthesis and microbiota in dextran sulfate sodium-treated rats. J Nutr 136:1558–1564PubMedGoogle Scholar
  21. Flisikowska T, Merkl C, Landmann M, Eser S, Rezaei N, Cui X, Kurome M, Zakhartchenko V, Kessler B, Wieland H, Rottmann O, Schmid RM, Schneider G, Kind A, Wolf E, Saur D, Schnieke A (2012) A porcine model of familial adenomatous polyposis. Gastroenterology 143:1173–1175PubMedCrossRefGoogle Scholar
  22. Gao R, Gao Z, Huang L, Qin H (2017) Gut microbiota and colorectal cancer. Eur J Clin Microbiol Infect Dis. doi:10.1007/s10096-016-2881-8 PubMedCentralGoogle Scholar
  23. Gonzalez LM, Moeser AJ, Blikslager AT (2015) Porcine models of digestive disease: the future of large animal translational research. Transl Res 166:12–27PubMedPubMedCentralCrossRefGoogle Scholar
  24. Goyal N, Rana A, Ahlawat A, Bijjem KR, Kumar P (2014) Animal models of inflammatory bowel disease: a review. Inflammopharmacology 22:219–233PubMedCrossRefGoogle Scholar
  25. Hamard A, Mazurais D, Boudry G, Le Huërou-Luron I, Sève B, Le Floc’h N (2010) A moderate threonine deficiency affects gene expression profile, paracellular permeability and glucose absorption capacity in the ileum of piglets. J Nutr Biochem 21:914–921PubMedCrossRefGoogle Scholar
  26. Haynes TE, Li P, Li X, Shimotori K, Sato H, Flynn NE, Wang J, Knabe DA, Wu G (2009) l-Glutamine or l-alanyl-l-glutamine prevents oxidant- or endotoxin-induced death of neonatal enterocytes. Amino Acids 37:131–142PubMedCrossRefGoogle Scholar
  27. Heinritz SN, Mosenthin R, Weiss E (2013) Use of pigs as a potential model for research into dietary modulation of the human gut microbiota. Nutr Res Rev 26:191–209PubMedCrossRefGoogle Scholar
  28. Hou Y, Wu G (2017) Nutritionally nonessential amino acids: a misnomer in nutritional sciences. Adv Nutr 8:137–139PubMedCrossRefGoogle Scholar
  29. Hou Y, Wang L, Zhang W, Yang Z, Ding B, Zhu H, Liu Y, Qiu Y, Yin Y, Wu G (2012) Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids 43:1233–1242PubMedCrossRefGoogle Scholar
  30. Hou Y, Wang L, Yi D, Ding B, Yang Z, Li J, Chen X, Qiu Y, Wu G (2013) N-acetylcysteine reduces inflammation in the small intestine by regulating redox, EGF and TLR4 signaling. Amino Acids 45:513–522PubMedCrossRefGoogle Scholar
  31. Hou Y, Wang L, Yi D, Wu G (2015a) N-acetylcysteine and intestinal health: a focus on its mechanism of action. Front Biosci (Landmark Ed) 20:872–891CrossRefGoogle Scholar
  32. Hou Y, Yin Y, Wu G (2015b) Dietary essentiality of “nutritionally non-essential amino acids” for animals and humans. Exp Biol Med (Maywood) 240:997–1007CrossRefGoogle Scholar
  33. Hou Y, Yao K, Yin Y, Wu G (2016) Endogenous synthesis of amino acids limits growth, lactation, and reproduction in animals. Adv Nutr 7:331–342PubMedPubMedCentralCrossRefGoogle Scholar
  34. Hou Y, Wu Z, Dai Z, Wang G, Wu G (2017) Protein hydrolysates in animal nutrition: industrial production, bioactive peptides, and functional significance. J Anim Sci Biotechnol 8:24PubMedPubMedCentralCrossRefGoogle Scholar
  35. Hu CA, Hou Y (2014) Mammalian P5CR and P5CDH: protein structure and disease association. SOJ Biochem 1:4CrossRefGoogle Scholar
  36. Hu CA, Bart Williams D, Zhaorigetu S, Khalil S, Wan G, Valle D (2008) Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes. Amino Acids 35:655–664PubMedPubMedCentralCrossRefGoogle Scholar
  37. Ji Y, Wu Z, Dai Z, Sun K, Zhang Q, Wu G (2016) Excessive l-cysteine induces vacuole-like cell death by activating endoplasmic reticulum stress and mitogen-activated protein kinase signaling in intestinal porcine epithelial cells. Amino Acids 48:149–156PubMedCrossRefGoogle Scholar
  38. Jiang P, Sangild PT (2014) Intestinal proteomics in pig models of necrotising enterocolitis, short bowel syndrome and intrauterine growth restriction. Proteom Clin Appl 8:700–714CrossRefGoogle Scholar
  39. Jiao N, Wu Z, Ji Y, Wang B, Dai Z, Wu G (2015) l-Glutamate enhances barrier and antioxidative functions in intestinal porcine epithelial cells. J Nutr 145:2258–2264PubMedCrossRefGoogle Scholar
  40. Kang P, Zhang L, Hou Y, Ding B, Yi D, Wang L, Zhu H, Liu Y, Yin Y, Wu G (2014) Effects of l-proline on the growth performance, and blood parameters in weaned lipopolysaccharide (LPS)-challenged pigs. Asian Australas J Anim Sci 27:1150–1156PubMedPubMedCentralCrossRefGoogle Scholar
  41. Kaser A, Zeissig S, Blumberg RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28:573–621PubMedPubMedCentralCrossRefGoogle Scholar
  42. Kim CJ, Kovacs-Nolan J, Yang C, Archbold T, Fan MZ, Mine Y (2009) l-Cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis. Biochim Biophys Acta 1790:1161–1169PubMedCrossRefGoogle Scholar
  43. Kim CJ, Kovacs-Nolan JA, Yang C, Archbold T, Fan MZ, Mine Y (2010) l-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate (DSS)-induced colitis. J Nutr Biochem 21:468–475PubMedCrossRefGoogle Scholar
  44. Kocher J, Bui T, Giri-Rachman E, Wen K, Li G, Yang X, Liu F, Tan M, Xia M, Zhong W, Jiang X, Yuan L (2014) Intranasal P particle vaccine provided partial cross-variant protection against human GII.4 norovirus diarrhea in gnotobiotic pigs. J Virol 88:9728–9743PubMedPubMedCentralCrossRefGoogle Scholar
  45. Komninou D, Leutzinger Y, Reddy BS, Richie JP Jr (2006) Methionine restriction inhibits colon carcinogenesis. Nutr Cancer 54:202–208PubMedCrossRefGoogle Scholar
  46. Konno Y, Ashida T, Inaba Y, Ito T, Tanabe H, Maemoto A, Ayabe T, Mizukami Y, Fujiya M, Kohgo Y (2012) Isoleucine, an essential amino acid, induces the expression of human β defensin 2 through the activation of the G-protein coupled receptor-ERK pathway in the intestinal epithelia. Food Nutr Sci 3:548–555CrossRefGoogle Scholar
  47. Koopmans SJ, van der Staay FJ, Le Floc’h N, Dekker R, van Diepen JT, Jansman AJ (2012) Effects of surplus dietary l-tryptophan on stress, immunology, behavior, and nitrogen retention in endotoxemic pigs. J Anim Sci 90:241–251PubMedCrossRefGoogle Scholar
  48. Kostopanagiotou G, Avgerinos ED, Markidou E, Voiniadis P, Chondros C, Theodoraki K, Smyrniotis V, Arkadopoulos N (2011) Protective effect of NAC preconditioning against ischemia–reperfusion injury in piglet small bowel transplantation: effects on plasma TNF, IL-8, hyaluronic acid, and NO. J Surg Res 168:301–305PubMedCrossRefGoogle Scholar
  49. Lenaerts K, Ceulemans LJ, Hundscheid IH, Grootjans J, Dejong CH, Olde Damink SW (2013) New insights in intestinal ischemia–reperfusion injury: implications for intestinal transplantation. Curr Opin Organ Transplant 18:298–303PubMedCrossRefGoogle Scholar
  50. Li P, Yin YL, Li D, Kim SW, Wu G (2007) Amino acids and immune function. Br J Nutr 98:237–252PubMedCrossRefGoogle Scholar
  51. Li M, Monaco MH, Wang M, Comstock SS, Kuhlenschmidt TB, Fahey GC Jr, Miller MJ, Kuhlenschmidt MS, Donovan SM (2014) Human milk oligosaccharides shorten rotavirus-induced diarrhea and modulate piglet mucosal immunity and colonic microbiota. ISME J 8:1609–1620PubMedPubMedCentralCrossRefGoogle Scholar
  52. Li W, Sun K, Ji Y, Wu Z, Wang W, Dai Z, Wu G (2016) Glycine regulates expression and distribution of claudin-7 and ZO-3 proteins in intestinal porcine epithelial cells. J Nutr 146:964–969PubMedCrossRefGoogle Scholar
  53. Liu Y, Huang J, Hou Y, Zhu H, Zhao S, Ding B, Yin Y, Yi G, Shi J, Fan W (2008) Dietary arginine supplementation alleviates intestinal mucosal disruption induced by Escherichia coli lipopolysaccharide in weaned pigs. Br J Nutr 100:552–560PubMedCrossRefGoogle Scholar
  54. Ma Q, Wang Y, Gao X, Ma Z, Song Z (2007) l-Arginine reduces cell proliferation and ornithine decarboxylase activity in patients with colorectal adenoma and adenocarcinoma. Clin Cancer Res 13:7407–7412PubMedCrossRefGoogle Scholar
  55. Mao X, Zeng X, Qiao S, Wu G, Li D (2011) Specific roles of threonine in intestinal mucosal integrity and barrier function. Front Biosci (Elite Ed) 3:1192–1200Google Scholar
  56. Mao X, Qi S, Yu B, He J, Yu J, Chen D (2013) Zn(2+) and l-isoleucine induce the expressions of porcine β-defensins in IPEC-J2 cells. Mol Biol Rep 40:1547–1552PubMedCrossRefGoogle Scholar
  57. Mao X, Liu M, Tang J, Chen H, Chen D, Yu B, He J, Yu J, Zheng P (2015) Dietary leucine supplementation improves the mucin production in the jejunal mucosa of the weaned pigs challenged by porcine rotavirus. PLoS One 10:e0137380PubMedPubMedCentralCrossRefGoogle Scholar
  58. Messori S, Trevisi P, Simongiovanni A, Priori D, Bosi P (2013) Effect of susceptibility to enterotoxigenic Escherichia coli F4 and of dietary tryptophan on gut microbiota diversity observed in healthy young pigs. Vet Microbiol 162:173–179PubMedCrossRefGoogle Scholar
  59. Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V (2012) The pig: a model for human infectious diseases. Trends Microbiol 20:50–57PubMedCrossRefGoogle Scholar
  60. Meyer KF, Martins JL, de Freitas Filho LG, Oliva ML, Patrício FR, Macedo M, Wang L (2006) Glycine reduces tissue lipid peroxidation in hypoxia-reoxygenation-induced necrotizing enterocolitis in rats. Acta Cir Bras 21:161–167PubMedCrossRefGoogle Scholar
  61. O’Shea CJ, O’Doherty JV, Callanan JJ, Doyle D, Thornton K, Sweeney T (2016) The effect of algal polysaccharides laminarin and fucoidan on colonic pathology, cytokine gene expression and Enterobacteriaceae in a dextran sodium sulfate-challenged porcine model. J Nutr Sci 5:e15PubMedPubMedCentralCrossRefGoogle Scholar
  62. Peterson JW, Boldogh I, Popov VL, Saini SS, Chopra AK (1998) Anti-inflammatory and antisecretory potential of histidine in Salmonella-challenged mouse small intestine. Lab Invest 78:523–534PubMedGoogle Scholar
  63. Petrat F, Boengler K, Schulz R, de Groot H (2012) Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischemia–reperfusion injury: current knowledge. Br J Pharmacol 165:2059–2072PubMedPubMedCentralCrossRefGoogle Scholar
  64. Phang JM, Liu W, Hancock CN, Fischer JW (2015) Proline metabolism and cancer: emerging links to glutamine and collagen. Curr Opin Clin Nutr Metab Care 18:71–77PubMedCrossRefGoogle Scholar
  65. Pi D, Liu Y, Shi H, Li S, Odle J, Lin X, Zhu H, Chen F, Hou Y, Leng W (2014) Dietary supplementation of aspartate enhances intestinal integrity and energy status in weanling piglets after lipopolysaccharide challenge. J Nutr Biochem 25:456–462PubMedCrossRefGoogle Scholar
  66. Pouillart PR, Dépeint F, Abdelnour A, Deremaux L, Vincent O, Mazière JC, Madec JY, Chatelain D, Younes H, Wils D, Saniez MH, Dupas JL (2010) Nutriose, a prebiotic low-digestible carbohydrate, stimulates gut mucosal immunity and prevents TNBS-induced colitis in piglets. Inflamm Bowel Dis 16:783–794PubMedCrossRefGoogle Scholar
  67. Ramalingam A, Wang X, Gabello M, Valenzano MC, Soler AP, Ko A, Morin PJ, Mullin JM (2010) Dietary methionine restriction improves colon tight junction barrier function and alters claudin expression pattern. Am J Physiol Cell Physiol 299:C1028–C1035PubMedCrossRefGoogle Scholar
  68. Randhawa PK, Singh K, Singh N, Jaggi AS (2014) A review on chemical-induced inflammatory bowel disease models in rodents. Korean J Physiol Pharmacol 18:279–288PubMedPubMedCentralCrossRefGoogle Scholar
  69. Ren XR (2015) Regulatory effect of glutamic acid or glycine on intestinal mucosal immune barrier injury in piglets after lipopolysaccharide challenge. Dissertation, Wuhan Polytechnic UniversityGoogle Scholar
  70. Ren W, Zou L, Ruan Z, Li N, Wang Y, Peng Y, Liu G, Yin Y, Li T, Hou Y, Wu G (2013) Dietary l-proline supplementation confers immunostimulatory effects on inactivated Pasteurella multocida vaccine immunized mice. Amino Acids 45:555–561PubMedCrossRefGoogle Scholar
  71. Ren M, Zhang SH, Zeng XF, Liu H, Qiao SY (2015) Branched-chain amino acids are beneficial to maintain growth performance and intestinal immune-related function in weaned piglets fed protein restricted diet. Asian Australas J Anim Sci 28:1742–1750PubMedPubMedCentralCrossRefGoogle Scholar
  72. Rezaei R, Knabe DA, Tekwe CD, Dahanayaka S, Ficken MD, Fielder SE, Eide SJ, Lovering SL, Wu G (2013a) Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids 44:911–923PubMedCrossRefGoogle Scholar
  73. Rezaei R, Wang W, Wu Z, Dai Z, Wang J, Wu G (2013b) Biochemical and physiological bases for utilization of dietary amino acids by young Pigs. J Anim Sci Biotechnol 4:7PubMedPubMedCentralCrossRefGoogle Scholar
  74. Rezaei R, Wu Z, Hou Y, Bazer FW, Wu G (2016) Amino acids and mammary gland development: nutritional implications for milk production and neonatal growth. J Anim Sci Biotechnol 7:20PubMedPubMedCentralCrossRefGoogle Scholar
  75. Rhoads JM, Keku EO, Quinn J, Woosely J, Lecce JG (1991) l-Glutamine stimulates jejunal sodium and chloride absorption in pig rotavirus enteritis. Gastroenterology 100:683–691PubMedCrossRefGoogle Scholar
  76. Ruth MR, Field CJ (2013) The immune modifying effects of amino acids on gut-associated lymphoid tissue. J Anim Sci Biotechnol 4:27PubMedPubMedCentralCrossRefGoogle Scholar
  77. Shen YB, Weaver AC, Kim SW (2014) Effect of feed grade l-methionine on growth performance and gut health in nursery pigs compared with conventional dl-methionine. J Anim Sci 92:5530–5539PubMedCrossRefGoogle Scholar
  78. Song Zh, Tong G, Xiao K, le Jiao F, Ke Yl HuCh (2016) l-Cysteine protects intestinal integrity, attenuates intestinal inflammation and oxidant stress, and modulates NF-κB and Nrf2 pathways in weaned piglets after LPS challenge. Innate Immun 22:152–161PubMedCrossRefGoogle Scholar
  79. Souza M, Cheetham SM, Azevedo MS, Costantini V, Saif LJ (2007) Cytokine and antibody responses in gnotobiotic pigs after infection with human norovirus genogroup II.4 (HS66 strain). J Virol 81:9183–9192PubMedPubMedCentralCrossRefGoogle Scholar
  80. Spanos CP, Papaconstantinou P, Spanos P, Karamouzis M, Lekkas G, Papaconstantinou C (2007) The effect of l-arginine and aprotinin on intestinal ischemia–reperfusion injury. J Gastrointest Surg 11:247–255PubMedCrossRefGoogle Scholar
  81. Sun Y, Wu Z, Li W, Zhang C, Sun K, Ji Y, Wang B, Jiao N, He B, Wang W, Dai Z, Wu G (2015) Dietary l-leucine supplementation enhances intestinal development in suckling piglets. Amino Acids 47:1517–1525PubMedCrossRefGoogle Scholar
  82. Tan B, Li XG, Kong X, Huang R, Ruan Z, Yao K, Deng Z, Xie M, Shinzato I, Yin Y, Wu G (2009) Dietary l-arginine supplementation enhances the immune status in early-weaned piglets. Amino Acids 37:323–331PubMedCrossRefGoogle Scholar
  83. Tan B, Yin Y, Kong X, Li P, Li X, Gao H, Li X, Huang R, Wu G (2010) l-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells. Amino Acids 38:1227–1235PubMedCrossRefGoogle Scholar
  84. Tang Y, Tan B, Xiong X, Li F, Ren W, Kong X, Qiu W, Hardwidge PR, Yin Y (2015) Methionine deficiency reduces autophagy and accelerates death in intestinal epithelial cells infected with enterotoxigenic Escherichia coli. Amino Acids 47:2199–2204PubMedCrossRefGoogle Scholar
  85. Tian Y, Wang K, Fan Y, Wang Y, Sun L, Wang L, Wang J, Wang Z, Li J, Ye Y, Ji G (2016) Chemopreventive effect of dietary glutamine on colitis-associated colorectal cancer is associated with modulation of the DEPTOR/mTOR signaling pathway. Nutrients 8:261PubMedCentralCrossRefGoogle Scholar
  86. Tossou MC, Liu H, Bai M, Chen S, Cai Y, Duraipandiyan V, Liu H, Adebowale TO, Al-Dhabi NA, Long L, Tarique H, Oso AO, Liu G, Yin Y (2016) Effect of high dietary tryptophan on intestinal morphology and tight junction protein of weaned pig. Biomed Res Int 2016:2912418PubMedPubMedCentralCrossRefGoogle Scholar
  87. Trevisi P, Melchior D, Mazzoni M, Casini L, De Filippi S, Minieri L, Lalatta-Costerbosa G, Bosi P (2009) A tryptophan-enriched diet improves feed intake and growth performance of susceptible weanling pigs orally challenged with Escherichia coli K88. J Anim Sci 87:148–156PubMedCrossRefGoogle Scholar
  88. Trevisi P, Corrent E, Mazzoni M, Messori S, Priori D, Gherpelli Y, Simongiovanni A, Bosi P (2015) Effect of added dietary threonine on growth performance, health, immunity and gastrointestinal function of weaning pigs with differing genetic susceptibility to Escherichia coli infection and challenged with E. coli K88ac. J Anim Physiol Anim Nutr (Berl) 99:511–520CrossRefGoogle Scholar
  89. Tsune I, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Takei Y, Sato N (2003) Dietary glycine prevents chemical-induced experimental colitis in the rat. Gastroenterology 125:775–785PubMedCrossRefGoogle Scholar
  90. Verma N, Rettenmeier AW, Schmitz-Spanke S (2011) Recent advances in the use of Sus scrofa (pig) as a model system for proteomic studies. Proteomics 11:776–793PubMedCrossRefGoogle Scholar
  91. Vermeulen MA, de Jong J, Vaessen MJ, van Leeuwen PA, Houdijk AP (2011) Glutamate reduces experimental intestinal hyperpermeability and facilitates glutamine support of gut integrity. World J Gastroenterol 17:1569–1573PubMedPubMedCentralCrossRefGoogle Scholar
  92. Wang X (2006) The effects of threonine on protein synthesis and immune function in intestinal mucosal of weaned piglets. Dissertation, China Agricultural UniversityGoogle Scholar
  93. Wang XY (2015) Regulative effect of glutamate on intestinal injury and muscle protein synthesis and degradation of piglets after lipopolysaccharide challenge. Dissertation, Wuhan Polytechnic UniversityGoogle Scholar
  94. Wang X, Qiao SY, Liu M, Ma YX (2006) Effects of graded levels of true ileal digestible threonine on performance, serum parameters and immune function of 10–25 kg pigs. Anim Feed Sci Technol 129:264–278CrossRefGoogle Scholar
  95. Wang W, Zeng X, Mao X, Wu G, Qiao S (2010) Optimal dietary true ileal digestible threonine for supporting the mucosal barrier in small intestine of weanling pigs. J Nutr 140:981–986PubMedCrossRefGoogle Scholar
  96. Wang XQ, Zeng PL, Feng Y, Zhang CM, Yang JP, Shu G, Jiang QY (2012) Effects of dietary lysine levels on apparent nutrient digestibility and cationic amino acid transporter mRNA abundance in the small intestine of finishing pigs, Sus scrofa. Anim Sci J 83:148–155PubMedCrossRefGoogle Scholar
  97. Wang Q, Hou Y, Yi D, Wang L, Ding B, Chen X, Long M, Liu Y, Wu G (2013a) Protective effects of N-acetylcysteine on acetic acid-induced colitis in a porcine model. BMC Gastroenterol 13:133PubMedPubMedCentralCrossRefGoogle Scholar
  98. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G (2013b) Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids 45:463–477PubMedCrossRefGoogle Scholar
  99. Wang W, Dai Z, Wu Z, Lin G, Jia S, Hu S, Dahanayaka S, Wu G (2014a) Glycine is a nutritionally essential amino acid for maximal growth of milk-fed young pigs. Amino Acids 46:2037–2045PubMedCrossRefGoogle Scholar
  100. Wang W, Wu Z, Lin G, Hu S, Wang B, Dai Z, Wu G (2014b) Glycine stimulates protein synthesis and inhibits oxidative stress in pig small intestinal epithelial cells. J Nutr 144:1540–1548PubMedCrossRefGoogle Scholar
  101. Wang H, Ji Y, Wu G, Sun K, Sun Y, Li W, Wang B, He B, Zhang Q, Dai Z, Wu Z (2015a) l-Tryptophan activates mammalian target of rapamycin and enhances expression of tight junction proteins in intestinal porcine epithelial cells. J Nutr 145:1156–1162PubMedCrossRefGoogle Scholar
  102. Wang H, Zhang C, Wu G, Sun Y, Wang B, He B, Dai Z, Wu Z (2015b) Glutamine enhances tight-junction protein expression and modulates CRF signaling in the jejunum of weanling piglets. J Nutr 145:25–31PubMedCrossRefGoogle Scholar
  103. Wang J, Li GR, Tan BE, Xiong X, Kong XF, Xiao DF, Xu LW, Wu MM, Huang B, Kim SW, Yin YL (2015c) Oral administration of putrescine and proline during the suckling period improves epithelial restitution after early weaning in piglets. J Anim Sci 93:1679–1688PubMedCrossRefGoogle Scholar
  104. Wang X, Liu Y, Li S, Pi D, Zhu H, Hou Y, Shi H, Leng W (2015d) Asparagine attenuates intestinal injury, improves energy status and inhibits AMP-activated protein kinase signalling pathways in weaned piglets challenged with Escherichia coli lipopolysaccharide. Br J Nutr 114:553–565PubMedCrossRefGoogle Scholar
  105. Wang H, Liu Y, Shi H, Wang X, Zhu H, Pi D, Leng W, Li S (2016) Aspartate attenuates intestinal injury and inhibits TLR4 and NODs/NF-κB and p38 signaling in weaned pigs after LPS challenge. Eur J Nutr. doi:10.1007/s00394-016-1189-x Google Scholar
  106. Wu G (1997) Synthesis of citrulline and arginine from proline in enterocytes of postnatal pigs. Am J Physiol Gastrointest Liver Physiol 272:G1382–G1390Google Scholar
  107. Wu G (1998) Intestinal mucosal amino acid catabolism. J Nutr 128:1249–1252PubMedGoogle Scholar
  108. Wu G (2010) Functional amino acids in growth, reproduction and health. Adv Nutr 1:31–37PubMedPubMedCentralCrossRefGoogle Scholar
  109. Wu G (2013a) Functional amino acids in nutrition and health. Amino Acids 45:407–411PubMedCrossRefGoogle Scholar
  110. Wu G (2013b) Amino acids: biochemistry and nutrition. CRC Press, Boca RatonCrossRefGoogle Scholar
  111. Wu HT (2015) Regulative effect of glycine on intestinal injury and muscle protein synthesis and degradation of piglets after lipopolysaccharide challenge. Dissertation, Wuhan Polytechnic UniversityGoogle Scholar
  112. Wu G, Knabe DA (1994) Free and protein-bound amino acids in sow’s colostrum and milk. J Nutr 124:415–424PubMedGoogle Scholar
  113. Wu G, Knabe DA, Flynn NE (1994) Synthesis of citrulline from glutamine in pig enterocytes. Biochem J 299:115–121PubMedPubMedCentralCrossRefGoogle Scholar
  114. Wu G, Knabe DA, Flynn NE, Yan W, Flynn SP (1996a) Arginine degradation in developing porcine enterocytes. Am J Physiol Gastrointest Liver Physiol 271:G913–G919Google Scholar
  115. Wu G, Meier SA, Knabe DA (1996b) Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. J Nutr 126:2578–2584PubMedGoogle Scholar
  116. Wu G, Flynn NE, Knabe DA (2000a) Enhanced intestinal synthesis of polyamines from proline in cortisol-treated piglets. Am J Physiol Endocrinol Metab 279:E395–E402PubMedGoogle Scholar
  117. Wu G, Flynn NE, Knabe DA, Jaeger LA (2000b) A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes during weaning. Am J Physiol Regul Integr Comp Physiol 279:R554–R559PubMedGoogle Scholar
  118. Wu G, Bazer FW, Burghardt RC, Johnson GA, Kim SW, Knabe DA, Li P, Li X, McKnight JR, Satterfield MC, Spencer TE (2011) Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids 40:1053–1063PubMedCrossRefGoogle Scholar
  119. Wu X, Zhang Y, Liu Z, Li TJ, Yin YL (2012) Effects of oral supplementation with glutamate or combination of glutamate and N-carbamylglutamate on intestinal mucosa morphology and epithelium cell proliferation in weanling piglets. J Anim Sci 90:337–339PubMedCrossRefGoogle Scholar
  120. Wu G, Bazer FW, Dai Z, Li D, Wang J, Wu Z (2014) Amino acid nutrition in animals: protein synthesis and beyond. Annu Rev Anim Biosci 2:387–417PubMedCrossRefGoogle Scholar
  121. Wu Z, Hu CA, Wu G, Zhaorigetu S, Chand H, Sun K, Ji Y, Wang B, Dai Z, Walton B, Miao Y, Hou Y (2015) Intimacy and deadly feud: the interplay of autophagy and apoptosis mediated by amino acids. Amino Acids 47:2089–2099PubMedCrossRefGoogle Scholar
  122. Xu CC, Yang SF, Zhu LH, Cai X, Sheng YS, Zhu SW, Xu JX (2014) Regulation of N-acetylcysteine on gut redox status and major microbiota in weaned piglets. J Anim Sci 92:1504–1511PubMedCrossRefGoogle Scholar
  123. Yandza T, Tauc M, Saint-Paul MC, Ouaissi M, Gugenheim J, Hébuterne X (2012) The pig as a preclinical model for intestinal ischemia–reperfusion and transplantation studies. J Surg Res 178:807–819PubMedCrossRefGoogle Scholar
  124. Yang KM, Jiang ZY, Zheng CT, Wang L, Yang XF (2014) Effect of Lactobacillus plantarum on diarrhea and intestinal barrier function of young piglets challenged with enterotoxigenic Escherichia coli K88. J Anim Sci 92:1496–1503PubMedCrossRefGoogle Scholar
  125. Yao K, Guan S, Li T, Huang R, Wu G, Ruan Z, Yin Y (2011) Dietary l-arginine supplementation enhances intestinal development and expression of vascular endothelial growth factor in weanling piglets. Br J Nutr 105:703–709PubMedCrossRefGoogle Scholar
  126. Yi GF, Carroll JA, Allee GL, Gaines AM, Kendall DC, Usry JL, Toride Y, Izuru S (2005) Effect of glutamine and spray-dried plasma on growth performance, small intestinal morphology, and immune responses of Escherichia coli K88+-challenged weaned pigs. J Anim Sci 83:634–643PubMedCrossRefGoogle Scholar
  127. Yi D, Hou Y, Wang L, Ouyang W, Long M, Zhao D, Ding B, Liu Y, Wu G (2015) l-Glutamine enhances enterocyte growth via activation of the mTOR signaling pathway independently of AMPK. Amino Acids 47:65–78PubMedCrossRefGoogle Scholar
  128. Yi D, Hou Y, Wang L, Long M, Hu S, Mei H, Yan L, Hu CA, Wu G (2016) N-Acetylcysteine stimulates protein synthesis in enterocytes independently of glutathione synthesis. Amino Acids 48:523–533PubMedCrossRefGoogle Scholar
  129. Yi D, Hou YQ, Xiao H, Wang L, Zhang Y, Chen HB, Wu T, Ding BY, Hu CA, Wu GY (2017) N-Acetylcysteine improves intestinal function in lipopolysaccharides-challenged piglets through multiple signaling pathways. Amino Acids. doi:10.1007/s00726-017-2389-2 Google Scholar
  130. Zhang S, Qiao S, Ren M, Zeng X, Ma X, Wu Z, Thacker P, Wu G (2013) Supplementation with branched-chain amino acids to a low-protein diet regulates intestinal expression of amino acid and peptide transporters in weanling pigs. Amino Acids 45:1191–1205PubMedCrossRefGoogle Scholar
  131. Zhang S, Ren M, Zeng X, He P, Ma X, Qiao S (2014) Leucine stimulates ASCT2 amino acid transporter expression in porcine jejunal epithelial cell line (IPEC-J2) through PI3K/Akt/mTOR and ERK signaling pathways. Amino Acids 46:2633–2642PubMedCrossRefGoogle Scholar
  132. Zhang SX, Li L, Yin JW, Jin M, Kong XY, Pang LL, Zhou YK, Tian LG, Chen JX, Zhou XN (2016) Emergence of human caliciviruses among diarrhea cases in southwest China. BMC Infect Dis 16:511PubMedPubMedCentralCrossRefGoogle Scholar
  133. Zhang Y, Lu T, Han L, Zhao L, Niu Y, Chen H (2017) l-Glutamine supplementation alleviates constipation during late gestation of mini sows by modifying the microbiota composition in feces. Biomed Res Int 2017:4862861PubMedPubMedCentralGoogle Scholar
  134. Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M, Bunzendaul H, Bradford B, Lemasters JJ (2003) l-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Curr Opin Clin Nutr Metab Care 6:229–240PubMedCrossRefGoogle Scholar
  135. Zhong H, Li H, Liu G, Wan H, Mercier Y, Zhang X, Lin Y, Che L, Xu S, Tang L, Tian G, Chen D, Wu D, Fang Z (2016) Increased maternal consumption of methionine as its hydroxyl analog promoted neonatal intestinal growth without compromising maternal energy homeostasis. J Anim Sci Biotechnol 7:46PubMedPubMedCentralCrossRefGoogle Scholar
  136. Zhou ZY, Wan XY, Cao JW (2013) Dietary methionine intake and risk of incident colorectal cancer: a meta-analysis of 8 prospective studies involving 431,029 participants. PLoS One 8:e83588PubMedPubMedCentralCrossRefGoogle Scholar
  137. Zhu HL, Liu YL, Xie XL, Huang JJ, Hou YQ (2013) Effect of l-arginine on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge. Innate Immun 19:242–252PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria 2017

Authors and Affiliations

  • Yulan Liu
    • 1
  • Xiuying Wang
    • 1
  • Yongqing Hou
    • 1
  • Yulong Yin
    • 2
    • 3
  • Yinsheng Qiu
    • 1
  • Guoyao Wu
    • 4
  • Chien-An Andy Hu
    • 1
    • 2
    • 3
    • 5
  1. 1.Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed ScienceWuhan Polytechnic UniversityWuhanChina
  2. 2.Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical AgricultureThe Chinese Academy of SciencesChangshaChina
  3. 3.Institute of Life SciencesHuman Normal UniversityChangshaChina
  4. 4.Department of Animal ScienceTexas A&M UniversityCollege StationUSA
  5. 5.Department of Biochemistry and Molecular BiologyUniversity of New Mexico School of MedicineAlbuquerqueUSA

Personalised recommendations