Skip to main content
SpringerLink
Log in

Dietary l-glutamine supplementation increases Pasteurella multocida burden and the expression of its major virulence factors in mice

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

This study was conducted to determine the effects of graded doses of l-glutamine supplementation on the replication and distribution of Pasteurella multocida, and the expression of its major virulence factors in mouse model. Mice were randomly assigned to the basal diet supplemented with 0, 0.5, 1.0 or 2.0 % glutamine. Pasteurella multocida burden was detected in the heart, liver, spleen, lung and kidney after 12 h of P. multocida infection. The expression of major virulence factors, toll-like receptors (TLRs), proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha) and anti-oxidative factors (GPX1 and CuZnSOD) was analyzed in the lung and spleen. Dietary 0.5 % glutamine supplementation has little significant effect on these parameters, compared to those with basal diet. However, results showed that a high dose of glutamine supplementation increased the P. multocida burden (P < 0.001) and the expression of its major virulence factors (P < 0.05) as compared to those with a lower dose of supplementation. In the lung, high dose of glutamine supplementation inhibited the proinflammatory responses (P < 0.05) and TLRs signaling (P < 0.05). In the spleen, the effect of glutamine supplementation on different components in TLR signaling depends on glutamine concentration, and high dose of glutamine supplementation activated the proinflammatory response. In conclusion, glutamine supplementation increased P. multocida burden and the expression of its major virulence factors, while affecting the functions of the lung and spleen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

IL-1 β:

Interleukin-1 beta

IL-6:

Interleukin-6

TNF-α:

Tumor necrosis factor alpha

References

  • Ban K, Sprunt JM, Martin S et al (2011) Glutamine activates peroxisome proliferator-activated receptor-gamma in intestinal epithelial cells via 15-S-HETE and 13-OXO-ODE: a novel mechanism. Am J Physiol Gastrointest Liver Physiol 301:G547–G554

    Article  PubMed  CAS  Google Scholar 

  • Bensaci J, Curis E, Nicolis I et al (2012) An in silico model of enterocytic glutamine to citrulline conversion pathway. Amino Acids 43:1727–1737

    Article  PubMed  CAS  Google Scholar 

  • Bonetto A, Penna F, Minero VG et al (2011) Glutamine prevents myostatin hyperexpression and protein hypercatabolism induced in C2C12 myotubes by tumor necrosis factor-alpha. Amino Acids 40:585–594

    Article  PubMed  CAS  Google Scholar 

  • Boutry C, Matsumoto H, Bos C et al (2012) Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect? Amino Acids 43:1485–1498

    Article  PubMed  CAS  Google Scholar 

  • Brasse-Lagnel CG, Lavoinne AM, Husson AS (2010) Amino acid regulation of mammalian gene expression in the intestine. Biochimie 92:729–735

    Article  PubMed  CAS  Google Scholar 

  • Chiu M, Tardito S, Barilli A et al (2012) Glutamine stimulates mTORC1 independent of the cell content of essential amino acids. Amino Acids 43:2561–2567

    Article  PubMed  CAS  Google Scholar 

  • Cooksey RC, McClain DA (2011) Increased hexosamine pathway flux and high fat feeding are not additive in inducing insulin resistance: evidence for a shared pathway. Amino Acids 40:841–846

    Article  PubMed  CAS  Google Scholar 

  • Dai ZL, Zhang J, Wu G et al (2010) Utilization of amino acids by bacteria from the pig small intestine. Amino Acids 39:1201–1215

    Article  PubMed  CAS  Google Scholar 

  • Dai ZL, Wu G, Zhu WY (2011) Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci 16:1768–1786

    Article  CAS  Google Scholar 

  • Dai ZL, Li XL, Xi PB et al (2012a) Metabolism of select amino acids in bacteria from the pig small intestine. Amino Acids 42:1597–1608

    Article  PubMed  CAS  Google Scholar 

  • Dai ZL, Li XL, Xi PB et al (2012b) Regulatory role for l-arginine in the utilization of amino acids by pig small-intestinal bacteria. Amino Acids 43:233–244

    Article  PubMed  CAS  Google Scholar 

  • Dai ZL, Li XL, Xi PB et al (2013) l-Glutamine regulates amino acid utilization by intestinal bacteria. Amino Acids. doi:10.1007/s00726-012-1264-4

    Google Scholar 

  • Ewaschuk JB, Murdoch GK, Johnson IR et al (2011) Glutamine supplementation improves intestinal barrier function in a weaned piglet model of Escherichia coli infection. Br J Nutr 106:870–877

    Article  PubMed  CAS  Google Scholar 

  • Fu WJ, Stromberg AJ, Viele K et al (2010) Statistics and bioinformatics in nutritional sciences: analysis of complex data in the era of systems biology. J Nutr Biochem 21:561–572

    Article  PubMed  CAS  Google Scholar 

  • Geng MM, Li TJ, Kong XF et al (2011) Reduced expression of intestinal N-acetylglutamate synthase in suckling piglets: a novel molecular mechanism for arginine as a nutritionally essential amino acid for neonates. Amino Acids 40:1513–1522

    Article  PubMed  CAS  Google Scholar 

  • Hagen SJ, Ohtani M, Zhou JR et al (2009) Inflammation and foveolar hyperplasia are reduced by supplemental dietary glutamine during Helicobacter pylori infection in mice. J Nutr 139:912–918

    Article  PubMed  CAS  Google Scholar 

  • Holecek M, Kandar R, Sispera L et al (2011) Acute hyperammonemia activates branched-chain amino acid catabolism and decreases their extracellular concentrations: different sensitivity of red and white muscle. Amino Acids 40:575–584

    Article  PubMed  CAS  Google Scholar 

  • Hou YQ, Wang L, Ding BY et al (2011) Alpha-ketoglutarate and intestinal function. Front Biosci 16:1186–1196

    Article  CAS  Google Scholar 

  • Hou YQ, Wang L, Zhang W et al (2012) Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids 43:1233–1242

    Article  PubMed  CAS  Google Scholar 

  • Jayaraman P, Sada-Ovalle I, Nishimura T et al (2013) IL-1beta promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation. J Immunol 190:4196–4204

    Article  PubMed  CAS  Google Scholar 

  • Kretzmann NA, Fillmann H, Mauriz JL et al (2008) Effects of glutamine on proinflammatory gene expression and activation of nuclear factor kappa B and signal transducers and activators of transcription in TNBS-induced colitis. Inflamm Bowel Dis 14:1504–1513

    Article  PubMed  Google Scholar 

  • Lei J, Feng DY, Zhang YL et al (2012) Regulation of leucine catabolism by metabolic fuels in mammary epithelial cells. Amino Acids 43:2179–2189

    Article  PubMed  CAS  Google Scholar 

  • Li P, Yin YL, Li D et al (2007) Amino acids and immune function. Br J Nutr 98:237–252

    Article  PubMed  CAS  Google Scholar 

  • Li XL, Rezaei R, Li P et al (2011a) Composition of amino acids in feed ingredients for animal diets. Amino Acids 40:1159–1168

    Article  PubMed  CAS  Google Scholar 

  • Li FN, Yin YL, Tan BE et al (2011b) Leucine nutrition in animals and humans: mTOR signaling and beyond. Amino Acids 41:1185–1193

    Article  PubMed  CAS  Google Scholar 

  • Li XQ, Zhu YH, Zhang HF et al (2012) Risks associated with high-dose Lactobacillus rhamnosus in an Escherichia coli model of piglet diarrhoea: intestinal microbiota and immune imbalances. PLoS One 7:e40666

    Article  PubMed  CAS  Google Scholar 

  • Medzhitov R (2007) Recognition of microorganisms and activation of the immune response. Nature 449:819–826

    Article  PubMed  CAS  Google Scholar 

  • Miller YI, Choi SH, Wiesner P et al (2012) The SYK side of TLR4: signalling mechanisms in response to LPS and minimally oxidized LDL. Br J Pharmacol 167:990–999

    Article  PubMed  CAS  Google Scholar 

  • Perez-Barcena J, Crespi C, Regueiro V et al (2010) Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit. Crit Care 14:R233

    Article  PubMed  Google Scholar 

  • Ren W, Luo W, Wu M et al (2011) Dietary l-glutamine supplementation improves pregnancy outcome in mice infected with type-2 porcine circovirus. Amino Acids. doi:10.1007/s00726-011-1134-5

    Google Scholar 

  • Ren WK, Liu G, Li TJ et al (2012a) Dietary supplementation with arginine and glutamine confers a positive effect in porcine circovirus-infected pig. J Food Agric Environ 10:485–490

    CAS  Google Scholar 

  • Ren W, Yin YL, Liu G et al (2012b) Effect of dietary arginine supplementation on reproductive performance of mice with porcine circovirus type 2 infection. Amino Acids 42:2089–2094

    Article  PubMed  CAS  Google Scholar 

  • Ren W, Li Y, Yu X et al. (2013a) Glutamine modifies immune responses of mice infected with porcine circovirus type 2. Br J Nutr 1–8

  • Ren W, Zou L, Li N et al (2013b) Dietary arginine supplementation enhances immune responses to inactivated Pasteurella multocida vaccination in mice. Br J Nutr 109:867–872

    Article  PubMed  CAS  Google Scholar 

  • Ren W, Zou L, Ruan Z et al (2013c) Dietary l-proline supplementation confers immunostimulatory effects on inactivated Pasteurella multocida vaccine immunized mice. Amino Acids. doi:10.1007/s00726-013-1490-4

    Google Scholar 

  • Rezaei R, Knabe DA, Tekwe CD et al (2013a) Dietary supplementation with monosodium glutamate is safe and improves growth performance in postweaning pigs. Amino Acids 44:911–923

    Article  PubMed  CAS  Google Scholar 

  • Rezaei R, Wang WW, Wu ZL et al (2013b) Biochemical and physiological bases for utilization of dietary amino acids by young pigs. J Anim Sci Biotech 4:7

    Article  CAS  Google Scholar 

  • Rodrigues RS, Oliveira RA, Li Y et al (2013) Intestinal epithelial restitution after TcdB challenge and recovery from Clostridium difficile infection in mice with alanyl-glutamine treatment. J Infect Dis 207:1505–1515

    Article  PubMed  CAS  Google Scholar 

  • Tan BE, Yin YL, Kong XF et al (2010) l-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells. Amino Acids 38:1227–1235

    Article  PubMed  CAS  Google Scholar 

  • Tan BE, Li XG, Wu G et al (2012) Dynamic changes in blood flow and oxygen consumption in the portal-drained viscera of growing pigs receiving acute administration of l-arginine. Amino Acids 43:2481–2489

    Article  PubMed  CAS  Google Scholar 

  • Townsend KM, Boyce JD, Chung JY et al (2001) Genetic organization of Pasteurella multocida cap loci and development of a multiplex capsular PCR tying system. J Chin Microbiol 39:924–929

    Article  CAS  Google Scholar 

  • Wei JW, Carroll RJ, Harden KK et al (2012) Comparisons of treatment means when factors do not interact in two-factorial studies. Amino Acids 42:2031–2035

    Article  PubMed  CAS  Google Scholar 

  • Wilkie IW, Harper M, Boyce JD et al (2012) Pasteurella multocida: diseases and pathogenesis. Curr Top Microbiol Immunol 361:1–22

    Article  PubMed  CAS  Google Scholar 

  • Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17

    Article  PubMed  Google Scholar 

  • Wu G (2010a) Recent advances in swine amino acid nutrition. J Anim Sci Biotech 1:49–61

    Google Scholar 

  • Wu G (2010b) Functional amino acids in growth, reproduction and health. Adv Nutr 1:31–37

    Article  PubMed  CAS  Google Scholar 

  • Wu G (2013a) Amino acids: biochemistry and nutrition. CRC Press, Boca Raton

    Book  Google Scholar 

  • Wu G (2013b) Functional amino acids in nutrition and health. Amino Acids. doi:10.1007/s00726-013-1500-6

    Google Scholar 

  • Wu G, Flynn NE (1995) Regulation of glutamine and glucose metabolism by cell volume in lymphocytes and macrophages. Biochim Biophys Acta 1243:343–350

    Article  PubMed  Google Scholar 

  • Wu G, Meininger CJ (2009) Nitric oxide and vascular insulin resistance. Biofactors 35:21–27

    Article  PubMed  Google Scholar 

  • Wu G, Meier SA, Knabe DA (1996) Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. J Nutr 126:2578–2584

    PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Burghardt RC et al (2010) Impacts of amino acid nutrition on pregnancy outcome in pigs: mechanisms and implications for swine production. J Anim Sci 88:E195–E204

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Johnson GA et al (2011a) Important roles for l-glutamine in swine nutrition and production. J Anim Sci 89:2017–2030

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Bazer FW, Burghardt RC et al (2011b) Proline and hydroxyproline metabolism: implications for animal and human nutrition. Amino Acids 40:1053–1063

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Wu ZL, Dai ZL et al (2013) Dietary requirements of “nutritionally nonessential amino acids” by animals and humans. Amino Acids 44:1107–1113

    Article  PubMed  CAS  Google Scholar 

  • Xi P, Jiang Z, Zheng C et al (2011) Regulation of protein metabolism by glutamine: implications for nutrition and health. Front Biosci 16:578–597

    Article  CAS  Google Scholar 

  • Xi PB, Jiang ZY, Dai ZL et al (2012) Regulation of protein turnover by l-glutamine in porcine intestinal epithelial cells. J Nutr Biochem 23:1012–1017

    Article  PubMed  CAS  Google Scholar 

  • Yao K, Yin YL, Li XL et al (2012) Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells. Amino Acids 42:2491–2500

    Article  PubMed  CAS  Google Scholar 

  • Zhou XH, Wu X, Yin YL et al (2012) Preventive oral supplementation with glutamine and arginine has beneficial effects on the intestinal mucosa and inflammatory cytokines in endotoxemic rats. Amino Acids 43:813–821

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was jointly supported by National Basic Research Projects (2012CB124704 and 2009CB118800), Hunan Provincial Project (2013RS4065 and 2012GK4066), the National Science and Technology Support Program funding (2012BAD39B03), Comprehensive Strategic Cooperation projects from the Chinese Academy of Sciences and Guangdong Province (2012B091100210), Nanjing Branch Academy of Chinese Academy of Science and Jiangxi Province Cooperation Project, MATS-Beef Cattle Yak system (CARS-38), National Natural Science Foundation of China (30901041, 30972167, 30901040, 30928018, 30972156, 30871801, 30828024, 30828025, 30771558 and 30700581), National 863 Project (2008AA10Z316), the CAS/SAFEA International Partnership Program for Creative Research Teams, Texas AgriLife Research project (No. 8200), Ministry of Science and Technology of the People’s Republic of China(2010GB2D200322) and Hunan Provincial Natural Science Foundation of China (10JJ2028).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Chongqing Key Laboratory of Forage and Herbivorce, College of Animal Science and Technology, Southwest University, Chongqing, 400716, China

    Wenkai Ren, Shuping Liu, Fengmei Zhang, Nengzhang Li & Yuanyi Peng

  2. Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Hunan Provincial Engineering Research Center of Healthy Livestock, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, Hunan, China

    Wenkai Ren, Shuai Chen, Jie Yin, Li Wu, Gang Liu, Yulong Yin & Guoyao Wu

  3. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA

    Guoyao Wu

Authors
  1. Wenkai Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuai Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fengmei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nengzhang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jie Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yuanyi Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Li Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yulong Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guoyao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yuanyi Peng or Yulong Yin.

Additional information

W. Ren and S. Liu contributed equally to the present study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ren, W., Liu, S., Chen, S. et al. Dietary l-glutamine supplementation increases Pasteurella multocida burden and the expression of its major virulence factors in mice. Amino Acids 45, 947–955 (2013). https://doi.org/10.1007/s00726-013-1551-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-013-1551-8

Keywords

Search

Navigation