Skip to main content
SpringerLink
Log in
Book cover

L-Arginine in Clinical Nutrition pp 331–342Cite as

l-Arginine and Inflammatory Bowel Diseases (IBD)

  • Chapter
  • First Online:

Part of the book series: Nutrition and Health ((NH))

Abstract

Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the gastrointestinal tract and include Crohn’s disease (CD) and ulcerative colitis (UC). Although both are chronically relapsing illnesses, each is distinct in its presentation and course. CD causes transmural inflammation and affects all parts of the gastrointestinal tract, while UC is characterized by mucosal inflammation and is limited to the colon (Abraham and Cho, N Engl J Med 361:2066–2078, 2009). While the pathogenesis of IBD remains unclear, increasing evidence indicates that alterations in an individual’s genetic susceptibility, external environment, intestinal microbial flora, and immune response may all play a role (Danese and Fiocchi, World J Gastroenterol 12:4807–4812, 2006; Kugathasan and Fiocchi, Semin Pediatr Surg 16:146–153, 2007; Zhang and Li, World J Gastroenterol 20:91–99, 2014). Since IBD is a global healthcare problem that is consistently becoming more prevalent (Xavier and Podolsky, Nature 448:427–434, 2007), effective therapeutic strategies continue to be investigated. Since an imbalance between pro-inflammatory mediators, i.e., reactive oxygen mediators and cytokines, and anti-inflammatory responses is considered to be a key factor in the development and perpetuation of IBD (Cho, Nat Rev Immunol 8:458–466, 2008), current treatments usually include anti-inflammatory agents such as immunomodulators and biologic agents (Yamamoto, Curr Opin Gastroenterol 29:216–221, 2013). Nutrients, which can control the pro-inflammatory response, have been shown to be beneficial in models of spontaneous and induced colitis (Rutgeerts et al., Gastroenterology 136:1182–1197, 2009; Ren et al., Eur J Inflamm 11: 315–326, 2013). Notably, compelling evidence has indicated that l-arginine might be a good candidate for the low-risk treatment of IBD (Ren et al., Eur J Inflamm 11: 315–326, 2013; Coeffier et al., Inflamm Bowel Dis 16:518–524, 2010).

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361:2066–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Danese S, Fiocchi C. Etiopathogenesis of inflammatory bowel diseases. World J Gastroenterol. 2006;12:4807–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Kugathasan S, Fiocchi C. Progress in basic inflammatory bowel disease research. Semin Pediatr Surg. 2007;16:146–53.

    Article  PubMed  Google Scholar 

  4. Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol. 2014;20:91–9.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–34.

    Article  CAS  PubMed  Google Scholar 

  6. Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol. 2008;8:458–66.

    Article  CAS  PubMed  Google Scholar 

  7. Yamamoto T. Nutrition and diet in inflammatory bowel disease. Curr Opin Gastroenterol. 2013;29:216–21.

    Article  CAS  PubMed  Google Scholar 

  8. Rutgeerts P, Vermeire S, Van Assche G. Biological therapies for inflammatory bowel diseases. Gastroenterology. 2009;136:1182–97.

    Article  CAS  PubMed  Google Scholar 

  9. Ren WK, Yin J, Zhu XP, Liu G, Li NZ, et al. Glutamine on intestinal inflammation: a mechanistic perspective. Eur J Inflam. 2013;11:315–26.

    CAS  Google Scholar 

  10. Coeffier M, Marion-Letellier R, Dechelotte P. Potential for amino acids supplementation during inflammatory bowel diseases. Inflamm Bowel Dis. 2010;16:518–24.

    Article  PubMed  Google Scholar 

  11. Mane J, Fernandez-Banares F, Ojanguren I, Castella E, Bertran X, et al. Effect of l-arginine on the course of experimental colitis. Clin Nutr. 2001;20:415–22.

    Article  CAS  PubMed  Google Scholar 

  12. Singh K, Coburn LA, Barry DP, Asim M, Scull BP, et al. Deletion of cationic amino acid transporter 2 exacerbates dextran sulfate sodium colitis and leads to an IL-17-predominant T cell response. Am J Physiol Gastrointest Liver Physiol. 2013;305:G225–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hong SK, Maltz BE, Coburn LA, Slaughter JC, Chaturvedi R, et al. Increased serum levels of l-arginine in ulcerative colitis and correlation with disease severity. Inflamm Bowel Dis. 2010;16:105–11.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Coburn LA, Gong X, Singh K, Asim M, Scull BP, et al. l-arginine supplementation improves responses to injury and inflammation in dextran sulfate sodium colitis. PLoS One. 2012;7:e33546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ren W, Yin J, Wu M, Liu G, Yang G, et al. Serum amino acids profile and the beneficial effects of l-arginine or L-glutamine supplementation in dextran sulfate sodium colitis. PLoS One. 2014;9:e88335.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Xie F, Sun S, Xu A, Zheng S, Xue M, et al. Advanced oxidation protein products induce intestine epithelial cell death through a redox-dependent, c-jun N-terminal kinase and poly (ADP-ribose) polymerase-1-mediated pathway. Cell Death Dis. 2014;5:e1006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gul M, Kayhan B, Elbe H, Dogan Z, Otlu A. Histological and biochemical effects of dexmedetomidine on Liver during an inflammatory bowel disease. Ultrastruct Pathol. 2013. doi:10.3109/01913123.2013.829150

  18. Ren WK, Yin YL, Liu G, Yu XL, Li YH, et al. Effect of dietary l-arginine supplementation on reproductive performance of mice with porcine circovirus type 2 infection. Amino Acids. 2012;42:2089–94.

    Article  CAS  PubMed  Google Scholar 

  19. Ren WK, Zou LX, Li NZ, Wang Y, Liu G, et al. Dietary l-arginine supplementation enhances immune responses to inactivated Pasteurella multocida vaccination in mice. Br J Nutr. 2013;109:867–72.

    Article  CAS  PubMed  Google Scholar 

  20. Abreu MT, Fukata M, Arditi M. TLR signaling in the gut in health and disease. J Immunol. 2005;174:4453–60.

    Article  CAS  PubMed  Google Scholar 

  21. Zhu HL, Liu YL, Xie XL, Huang JJ, Hou YQ. Effect of l-arginine on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge. Innate Immun. 2013;19:242–52.

    Article  CAS  PubMed  Google Scholar 

  22. Ren W, Chen S, Yin J, Duan J, Li T, et al. Dietary l-arginine supplementation of mice alters the microbial population and activates intestinal innate immunity. J Nutr. 2014;144(6):988–95.

    Article  CAS  PubMed  Google Scholar 

  23. Di Sabatino A, Biancheri P, Rovedatti L, MacDonald TT, Corazza GR. New pathogenic paradigms in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18:368–71.

    Article  PubMed  Google Scholar 

  24. Joossens M, Huys G, Cnockaert M, De Preter V, Verbeke K, et al. Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut. 2011;60:631–7.

    Article  PubMed  Google Scholar 

  25. Andoh A, Imaeda H, Aomatsu T, Inatomi O, Bamba S, et al. Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn’s disease using terminal restriction fragment length polymorphism analysis. J Gastroenterol. 2011;46:479–86.

    Article  PubMed  Google Scholar 

  26. Martinez C, Antolin M, Santos J, Torrejon A, Casellas F, et al. Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol. 2008;103:643–8.

    Article  PubMed  Google Scholar 

  27. Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut. 2004;53:685–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Dai ZL, Li XL, Xi PB, Zhang J, Wu G, et al. Regulatory role for l-arginine in the utilization of amino acids by pig small-intestinal bacteria. Amino Acids. 2012;43:233–44.

    Article  CAS  PubMed  Google Scholar 

  29. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. 2005;102:11070–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Crawford PA, Crowley JR, Sambandam N, Muegge BD, Costello EK, et al. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation. Proc Natl Acad Sci USA. 2009;106:11276–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Salim SY, Soderholm JD. Importance of disrupted intestinal barrier in inflammatory bowel diseases. Inflamm Bowel Dis. 2011;17:362–81.

    Article  PubMed  Google Scholar 

  32. Hering NA, Fromm M, Schulzke JD. Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics. J Physiol. 2012;590:1035–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Beutheu S, Ghouzali I, Galas L, Dechelotte P, Coeffier M. Glutamine and l-arginine improve permeability and tight junction protein expression in methotrexate-treated Caco-2 cells. Clin Nutr. 2013;32:863–9.

    Article  CAS  PubMed  Google Scholar 

  34. Wu G. Amino acids: metabolism, functions, and nutrition. Amino Acids. 2009;37:1–17.

    Article  PubMed  Google Scholar 

  35. Perner A, Rask-Madsen J. Review article: the potential role of nitric oxide in chronic inflammatory bowel disorders. Aliment Pharmacol Ther. 1999;13:135–44.

    Article  CAS  PubMed  Google Scholar 

  36. Kubes P. Inducible nitric oxide synthase: a little bit of good in all of us. Gut. 2000;47:6–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. Inflamm Bowel Dis. 2003;9:179–89.

    Article  PubMed  Google Scholar 

  38. Middleton SJ, Shorthouse M, Hunter JO. Increased nitric oxide synthesis in ulcerative colitis. Lancet. 1993;341:465–6.

    Article  CAS  PubMed  Google Scholar 

  39. Boughton-Smith NK, Evans SM, Hawkey CJ, Cole AT, Balsitis M, et al. Nitric oxide synthase activity in ulcerative colitis and Crohn’s disease. Lancet. 1993;342:338–40.

    Article  CAS  PubMed  Google Scholar 

  40. Kimura H, Hokari R, Miura S, Shigematsu T, Hirokawa M, et al. Increased expression of an inducible isoform of nitric oxide synthase and the formation of peroxynitrite in colonic mucosa of patients with active ulcerative colitis. Gut. 1998;42:180–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Guihot G, Guimbaud R, Bertrand V, Narcy-Lambare B, Couturier D, et al. Inducible nitric oxide synthase activity in colon biopsies from inflammatory areas: correlation with inflammation intensity in patients with ulcerative colitis but not with Crohn’s disease. Amino Acids. 2000;18:229–37.

    Article  CAS  PubMed  Google Scholar 

  42. Rachmilewitz D, Stamler JS, Bachwich D, Karmeli F, Ackerman Z, et al. Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn’s disease. Gut. 1995;36:718–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Godkin AJ, De Belder AJ, Villa L, Wong A, Beesley JE, et al. Expression of nitric oxide synthase in ulcerative colitis. Eur J Clin Invest. 1996;26:867–72.

    Article  CAS  PubMed  Google Scholar 

  44. Yamaguchi T, Yoshida N, Ichiishi E, Sugimoto N, Naito Y, et al. Differing effects of two nitric oxide synthase inhibitors on experimental colitis. Hepatogastroenterology. 2001;48:118–22.

    CAS  PubMed  Google Scholar 

  45. Kankuri E, Vaali K, Knowles RG, Lahde M, Korpela R, et al. Suppression of acute experimental colitis by a highly selective inducible nitric-oxide synthase inhibitor, N-[3-(aminomethyl)benzyl]acetamidine. J Pharmacol Exp Ther. 2001;298:1128–32.

    CAS  PubMed  Google Scholar 

  46. Kankuri E, Hamalainen M, Hukkanen M, Salmenpera P, Kivilaakso E, et al. Suppression of pro-inflammatory cytokine release by selective inhibition of inducible nitric oxide synthase in mucosal explants from patients with ulcerative colitis. Scand J Gastroenterol. 2003;38:186–92.

    Article  CAS  PubMed  Google Scholar 

  47. Pilichos CJ, Kouerinis IA, Zografos GC, Korkolis DP, Preza AA, et al. The effect of nitric oxide synthases inhibitors on inflammatory bowel disease in a rat model. In Vivo. 2004;18:513–6.

    CAS  PubMed  Google Scholar 

  48. Rumi G, Tsubouchi R, Nishio H, Kato S, Mozsik G, et al. Dual role of endogenous nitric oxide in development of dextran sodium sulfate-induced colitis in rats. J Physiol Pharmacol. 2004;55:823–36.

    CAS  PubMed  Google Scholar 

  49. Hogaboam CM, Jacobson K, Collins SM, Blennerhassett MG. The selective beneficial effects of nitric oxide inhibition in experimental colitis. Am J Physiol. 1995;268:G673–84.

    CAS  PubMed  Google Scholar 

  50. Rachmilewitz D, Karmeli F, Okon E, Bursztyn M. Experimental colitis is ameliorated by inhibition of nitric oxide synthase activity. Gut. 1995;37:247–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Neilly PJ, Kirk SJ, Gardiner KR, Anderson NH, Rowlands BJ. Manipulation of the l-arginine-nitric oxide pathway in experimental colitis. Br J Surg. 1995;82:1188–91.

    Article  CAS  PubMed  Google Scholar 

  52. Rachmilewitz D, Karmeli F, Okon E. Sulfhydryl blocker-induced rat colonic inflammation is ameliorated by inhibition of nitric oxide synthase. Gastroenterology. 1995;109:98–106.

    Article  CAS  PubMed  Google Scholar 

  53. Armstrong AM, Campbell GR, Gannon C, Kirk SJ, Gardiner KR. Oral administration of inducible nitric oxide synthase inhibitors reduces nitric oxide synthesis but has no effect on the severity of experimental colitis. Scand J Gastroenterol. 2000;35:832–8.

    CAS  PubMed  Google Scholar 

  54. Dobosz M, Mionskowska L, Dobrowolski S, Dymecki D, Makarewicz W, et al. Is nitric oxide and heparin treatment justified in inflammatory bowel disease? An experimental study. Scand J Clin Lab Invest. 1996;56:657–63.

    Article  CAS  PubMed  Google Scholar 

  55. Pfeiffer CJ, Qiu BS. Effects of chronic nitric oxide synthase inhibition on TNB-induced colitis in rats. J Pharm Pharmacol. 1995;47:827–32.

    Article  CAS  PubMed  Google Scholar 

  56. Yoshida Y, Iwai A, Itoh K, Tanaka M, Kato S, et al. Role of inducible nitric oxide synthase in dextran sulphate sodium-induced colitis. Aliment Pharmacol Ther. 2000;14 Suppl 1:26–32.

    Article  CAS  PubMed  Google Scholar 

  57. Videla S, Vilaseca J, Medina C, Mourelle M, Guarner F, et al. Modulatory effect of nitric oxide on mast cells during induction of dextran sulfate sodium colitis. Dig Dis Sci. 2007;52:45–51.

    Article  CAS  PubMed  Google Scholar 

  58. Kiss J, Lamarque D, Delchier JC, Whittle BJ. Time-dependent actions of nitric oxide synthase inhibition on colonic inflammation induced by trinitrobenzene sulphonic acid in rats. Eur J Pharmacol. 1997;336:219–24.

    Article  CAS  PubMed  Google Scholar 

  59. Weiss TS, Herfarth H, Obermeier F, Ouart J, Vogl D, et al. Intracellular polyamine levels of intestinal epithelial cells in inflammatory bowel disease. Inflamm Bowel Dis. 2004;10:529–35.

    Article  CAS  PubMed  Google Scholar 

  60. Gobert AP, Cheng Y, Akhtar M, Mersey BD, Blumberg DR, et al. Protective role of arginase in a mouse model of colitis. J Immunol. 2004;173:2109–17.

    Article  CAS  PubMed  Google Scholar 

  61. Horowitz S, Binion DG, Nelson VM, Kanaa Y, Javadi P, et al. Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2007;292:G1323–36.

    Article  CAS  PubMed  Google Scholar 

  62. Akazawa Y, Kubo M, Zhang R, Matsumoto K, Yan F, et al. Inhibition of arginase ameliorates experimental ulcerative colitis in mice. Free Radic Res. 2013;47:137–45.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Subtropical Agriculture, Chinese Academy of Sciences, Yuanda Road (Second) 644, Mapoling, Changsha, Hunan, China

    Wenkai Ren DVM, Gang Liu PhD, Shuai Chen BS & Yulong Yin PhD

Authors
  1. Wenkai Ren DVM
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gang Liu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shuai Chen BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yulong Yin PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Wenkai Ren DVM or Yulong Yin PhD .

Editor information

Editors and Affiliations

  1. Faculty of Science & Technology Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Department Nutrition and Dietetics Nutritional Sciences Division School of Biomedical & Health Sciences, King’s College London, London, United Kingdom

    Victor R. Preedy

  3. Nutritional Sciences Research Division Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Rajkumar Rajendram

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Ren, W., Liu, G., Chen, S., Yin, Y. (2017). l-Arginine and Inflammatory Bowel Diseases (IBD). In: Patel, V., Preedy, V., Rajendram, R. (eds) L-Arginine in Clinical Nutrition. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-26009-9_26

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26009-9_26

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-26007-5

  • Online ISBN: 978-3-319-26009-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation