Gastroenterology
Volume 132, Issue 2 , Pages 562-575 , February 2007

Soluble Proteins Produced by Probiotic Bacteria Regulate Intestinal Epithelial Cell Survival and Growth

  • Fang Yan

      Affiliations

    • Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee
    • Corresponding Author InformationAddress requests for reprints to: Fang Yan, MD, PhD, Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, 2215 Garland Avenue, MRB IV, Room 1035, Nashville, Tennessee 37232-0696. fax: (615) 343-5323.
  • ,
  • Hanwei Cao

      Affiliations

    • Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee
  • ,
  • Timothy L. Cover

      Affiliations

    • Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
    • Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
    • Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee
  • ,
  • Robert Whitehead

      Affiliations

    • Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
    • Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
  • ,
  • M. Kay Washington

      Affiliations

    • Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee
  • ,
  • D. Brent Polk

      Affiliations

    • Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee
    • Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee

Received 8 June 2006 ,Accepted 19 October 2006.

References 

  1. Sartor RB. Mucosal immunology and mechanisms of gastrointestinal inflammation. In:  Feldman M,  Friedman LS,  Sleisenger MH editor. 7th ed.. Sleisenger & Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management. Volume I:Philadelphia: Saunders; 2002;p. 21–51
  2. El-Assal ON, Besner GE. HB-EGF enhances restitution after intestinal ischemia/reperfusion via PI3K/Akt and MEK/ERK1/2 activation. Gastroenterology. 2005;129:609–625
  3. Matsuura M, Okazaki K, Nishio A, Nakase H, Tamaki H, Uchida K, et al. Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis. Gastroenterology. 2005;128:975–986
  4. McCole DF, Rogler G, Varki N, Barrett KE. Epidermal growth factor partially restores colonic ion transport responses in mouse models of chronic colitis. Gastroenterology. 2005;129:591–608
  5. Sinha A, Nightingale J, West KP, Berlanga-Acosta J, Playford RJ. Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. N Engl J Med. 2003;349:350–357
  6. Marini M, Bamias G, Rivera-Nieves J, Moskaluk CA, Hoang SB, Ross WG, et al. TNF-α neutralization ameliorates the severity of murine Crohn’s-like ileitis by abrogation of intestinal epithelial cell apoptosis. Proc Natl Acad Sci U S A. 2003;100:8366–8371
  7. Zeissig S, Bojarski C, Buergel N, Mankertz J, Zeitz M, Fromm M, et al. Down-regulation of epithelial apoptosis and barrier repair in active Crohn’s disease by tumor necrosis factor α antibody treatment. Gut. 2004;53:1295–1302
  8. Yan F, Polk DB. Commensal bacteria in the gut: learning who our friends are. Curr Opin Gastroenterol. 2004;20:565–571
  9. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126:1620–1633
  10. Lilly DM, Stillwell RH. Probiotics: Growth-promoting factors produced by microorganisms. Science. 1965;147:747–748
  11. Borody TJ, Warren EF, Leis S, Surace R, Ashman O. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol. 2003;37:42–47
  12. Dieleman LA, Goerres MS, Arends A, Sprengers D, Torrice C, Hoentjen F, et al. Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment. Gut. 2003;52:370–376
  13. Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, et al. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut. 2004;53:108–114
  14. Schultz M, Timmer A, Herfarth HH, Sartor RB, Vanderhoof JA, Rath HC. Lactobacillus GG in inducing and maintaining remission of Crohn’s disease. BMC Gastroenterol. 2004;4:5
  15. Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC). Gut. 2003;52:988–997
  16. Resta-Lenert S, Barrett KE. Probiotics and commensals reverse TNF-α- and IFN-γ-induced dysfunction in human intestinal epithelial cells. Gastroenterology. 2006;130:731–746
  17. Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA. Extracellular MUC3 mucin secretion follows adherence of Lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003;52:827–833
  18. Otte JM, Podolsky DK. Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am J Physiol Gastrointest Liver Physiol. 2004;286:G613–G626
  19. Yan F, Polk DB. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem. 2002;277:50959–50965
  20. Amaravadi R, Thompson CB. The survival kinases Akt and Pim as potential pharmacological targets. J Clin Invest. 2005;115:2618–2624
  21. Hanada M, Feng J, Hemmings BA. Structure, regulation and function of PKB/AKT—a major therapeutic target. Biochim Biophys Acta. 2004;1697:3–16
  22. Tao Y, Drabik KA, Waypa TS, Musch MW, Alverdy JC, Schneewind O, et al. Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells. Am J Physiol Cell Physiol. 2006;290:C1018–C1030
  23. Miettinen M, Vuopio-Varkila J, Varkila K. Production of human tumor necrosis factor α, interleukin-6, and interleukin-10 is induced by lactic acid bacteria. Infect Immun. 1996;64:5403–5405
  24. Yan F, John SK, Wilson G, Jones DS, Washington MK, Polk DB. Kinase suppressor of Ras protects intestinal epithelium from cytokine-mediated apoptosis during inflammation. J Clin Invest. 2004;114:1272–1280
  25. Yan F, John SK, Polk DB. Kinase suppressor of Ras determines survival of intestinal cells exposed to tumor necrosis factor. Cancer Res. 2001;61:8668–8675
  26. van Engeland M, Nieland LJ, Ramaekers FC, Schutte B, Reutelingsperger CP. Annexin V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry. 1998;31:1–9
  27. Trencia A, Perfetti A, Cassese A, Vigliotta G, Miele C, Oriente F, et al. Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action. Mol Cell Biol. 2003;23:4511–4521
  28. Ichikawa H, Kuroiwa T, Inagaki A, Shineha R, Nishihira T, Satomi S, et al. Probiotic bacteria stimulate gut epithelial cell proliferation in rat. Dig Dis Sci. 1999;44:2119–2123
  29. Sheng H, Shao J, Townsend CM, Evers BM. Phosphatidylinositol 3-kinase mediates proliferative signals in intestinal epithelial cells. Gut. 2003;52:1472–1478
  30. Tien MT, Girardin SE, Regnault B, Le Bourhis L, Dillies MA, Coppee JY, et al. Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells. J Immunol. 2006;176:1228–1237
  31. Gill HS, Rutherfurd KJ, Prasad J, Gopal PK. Enhancement of natural and acquired immunity by Lactobacillus rhamnosus (HN001), Lactobacillus acidophilus (HN017), and Bifidobacterium lactis (HN019). Br J Nutr. 2000;83:167–176
  32. Bousvaros A, Guandalini S, Baldassano RN, Botelho C, Evans J, Ferry GD, et al. A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis. 2005;11:833–839
  33. Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK. Lactobacillus sepsis associated with probiotic therapy. Pediatrics. 2005;115:178–181
  34. Apostolou E, Kirjavainen PV, Saxelin M, Rautelin H, Valtonen V, Salminen SJ, et al. Good adhesion properties of probiotics: a potential risk for bacteremia?. FEMS Immunol Med Microbiol. 2001;31:35–39
  35. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science. 2001;291:881–884
  36. Xu J, Bjursell MK, Himrod J, Deng S, Carmichael LK, Chiang HC, et al. A genomic view of the human-Bacteroides thetaiotaomicron symbiosis. Science. 2003;299:2074–2076
  37. Dotan I, Rachmilewitz D. Probiotics in inflammatory bowel disease: possible mechanisms of action. Curr Opin Gastroenterol. 2005;21:426–430
  38. Macpherson AJ, Uhr T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science. 2004;303:1662–1665
  39. Zhang Q, Mousdicas N, Yi Q, Al-Hassani M, Billings SD, Perkins SM, et al. Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor. J Clin Invest. 2005;115:2855–2861
  40. Knodler LA, Finlay BB, Steele-Mortimer O. The Salmonella effector protein SopB protects epithelial cells from apoptosis by sustained activation of Akt. J Biol Chem. 2005;280:9058–9064
  41. Kelly D, Campbell JI, King TP, Grant G, Jansson EA, Coutts AG, et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-g and RelA (Epub December 21, 2003). Nat Immunol. 2004;5:104–112
  42. Neish AS. Molecular aspects of intestinal epithelial cell-bacterial interactions that determine the development of intestinal inflammation. Inflamm Bowel Dis. 2004;10:159–168

 Supported by NIH grants DK 065744 (to F.Y.), DK56008 (to D.B.P.), and DK58404 (Vanderbilt University Digestive Disease Research Center); Atticus Trust; Vanderbilt University Medical Center Imaging Core Research Laboratory grant (CA-68485); and the Department of Veterans Affairs.

PII: S0016-5085(06)02477-2

doi: 10.1053/j.gastro.2006.11.022

Gastroenterology
Volume 132, Issue 2 , Pages 562-575 , February 2007