1887

Abstract

During the last few years, a substantial body of scientific evidence has accumulated suggesting that certain surface-associated and extracellular components produced by probiotic bacteria could be responsible for some of their mechanisms of action. These bacterial components would be able to directly interact with the host mucosal cells; they include exopolysaccharides, bacteriocins, lipoteichoic acids and surface-associated and extracellular proteins. Extracellular proteins include proteins that are actively transported to the bacterial surroundings through the cytoplasmic membrane, as well as those that are simply shed from the bacterial surface. Compared to the other bacterial components, the interactive ability of extracellular proteins/peptides has been less extensively studied. In this review, current findings supporting an interaction between extracellular proteins/peptides produced by probiotic bacteria (strains of the genera , and ) and host mucosal cells are discussed. Research needs and future trends are also considered.

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2010-11-01
2020-03-28
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References

  1. Abdelaziz D. H., Amr K., Am A. O.. 2010; Nlrc4/Ipaf/CLAN/CARD12: more than a flagellin sensor. Int J Biochem Cell Biol42:789–791
    [Google Scholar]
  2. Adams R. J., Heazlewood S. P., Gilshenan K. S., O'Brien M., McGuckin M. A., Florin T. H.. 2008; IgG antibodies against common gut bacteria are more diagnostic for Crohn's disease than IgG against mannan or flagellin. Am J Gastroenterol103:386–396
    [Google Scholar]
  3. Altenhoefer A., Oswald S., Sonnenborn U., Enders C., Schulze J., Hacker J., Oelschlaeger T. A.. 2004; The probiotic Escherichia coli strain Nissle 1917 interferes with invasion of human intestinal epithelial cells by different enteroinvasive bacterial pathogens. FEMS Immunol Med Microbiol40:223–229
    [Google Scholar]
  4. Anokhina I. V., Kravtsov E. G., Yashina N. V., Ermolaev A. V., Chesnokova V. L., Dalin M. V.. 2006a; Characterization of surface adhesins of lactobacilli used in production of probiotic preparations. Bull Exp Biol Med141:716–719
    [Google Scholar]
  5. Anokhina I. V., Kravtsov E. G., Yashina N. V., Ermolaev A. V., Chesnokova V. L., Dalin M. V.. 2006b; Surface adhesins of lactobacilli loosely connected to the cell wall and eliminated into the environment during culturing in liquid nutrient media. Bull Exp Biol Med142:609–613
    [Google Scholar]
  6. Antikainen J., Anton L., Sillanpaa J., Korhönen T. K.. 2002; Domains in the S-layer protein CbsA of Lactobacillus crispatus involved in adherence to collagens, laminin and lipoteichoic acids and in self-assembly. Mol Microbiol46:381–394
    [Google Scholar]
  7. Araya M., Morelli L., Reid G., Sanders M. E., Stanton C.. 2002; Guidelines for the evaluation of probiotics in foods. FAO/WHO report
    [Google Scholar]
  8. Arvola T., Laiho K., Torkkeli S., Mykkanen H., Salminen S., Maunula L., Isolauri E.. 1999; Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study. Pediatrics104:e64
    [Google Scholar]
  9. Asong J., Wolfert M. A., Maiti K. K., Miller D., Boons G. J.. 2009; Binding and cellular activation studies reveal that Toll-like receptor 2 can differentially recognize peptidoglycan from Gram-positive and Gram-negative bacteria. J Biol Chem284:8643–8653
    [Google Scholar]
  10. Bansal T., Alaniz R. C., Wood T. K., Jayaraman A.. 2010; The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci U S A107:228–233
    [Google Scholar]
  11. Barinov A., Loux V., Hammani A., Nicolas P., Langella P., Ehrlich D., Maguin E., van de Gutche M.. 2009; Prediction of surface exposed proteins in Streptococcus pyogenes, with a potential application to other Gram-positive bacteria. Proteomics9:61–73
    [Google Scholar]
  12. Båth K., Roos S., Wall T., Jonsson H.. 2005; The cell surface of Lactobacillus reuteri ATCC 55730 highlighted by identification of 126 extracellular proteins from the genome sequence. FEMS Microbiol Lett253:75–82
    [Google Scholar]
  13. Beck H. C., Madsen S. M., Glenting J., Petersen J., Israelsen H., Norrelykke M. R., Antonsson M., Hansen A. M.. 2009; Proteomic analysis of cell surface-associated proteins from probiotic Lactobacillus plantarum. FEMS Microbiol Lett297:61–66
    [Google Scholar]
  14. Benz I., Schmidt M. A.. 2002; Never say never again: protein glycosylation in pathogenic bacteria. Mol Microbiol45:267–276
    [Google Scholar]
  15. Berks B. C.. 1996; A common export pathway for proteins binding complex redox cofactors?. Mol Microbiol22:393–404
    [Google Scholar]
  16. Binet R., Letoffe S., Ghigo J. M., Delepelaire P., Wandersman C.. 1997; Protein secretion by Gram-negative bacterial ABC exporters – a review. Gene192:7–11
    [Google Scholar]
  17. Boesten R. J., de Vos W. M.. 2008; Interactomics in the human intestine: lactobacilli and bifidobacteria make a difference. J Clin Gastroenterol42:S163–S167
    [Google Scholar]
  18. Borody T. J.. 2000; “Flora power” – fecal bacteria cure chronic C. difficile diarrhea. Am J Gastroenterol95:3028–3029
    [Google Scholar]
  19. Borthakur A., Gill R. K., Tyagi S., Koutsouris A., Alrefai W. A., Hecht G. A., Ramaswamy K., Dudeja P. K.. 2007; Lactobacillus acidophilus secreted effector molecule(s) increase Cl/OH exchange activity in Caco-2 cells via PI-3 kinase mediated pathway. J Nutr138:1355–1359
    [Google Scholar]
  20. Buist G., Ridder A. N., Kok J., Kuipers O. P.. 2006; Different subcellular locations of secretome components of Gram-positive bacteria. Microbiology152:2867–2874
    [Google Scholar]
  21. Caballero-Franco C., Keller K., De Simone C., Chadee K.. 2007; The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol292:G315–G322
    [Google Scholar]
  22. Candela M., Biagi E., Centanni M., Turroni S., Vici M., Musiani F., Vitali B., Bergmann S., Hammerschmidt S., Brigidi P.. 2009; Bifidobacterial enolase, a cell surface receptor for human plasminogen involved in the interaction with the host. Microbiology155:3294–3303
    [Google Scholar]
  23. Castaldo C., Vastano V., Siciliano R. A., Candela M., Vici M., Muscariello L., Marasco R., Sacco M.. 2009; Surface displaced alfa-enolase of Lactobacillus plantarum is a fibronectin binding protein. Microb Cell Fact8:14
    [Google Scholar]
  24. Chen X., Xu J., Shuai J., Chen J., Zhang Z., Fang W.. 2007; The S-layer proteins of Lactobacillus crispatus strain ZJ001 is responsible for competitive exclusion against Escherichia coli O157: H7 and Salmonella typhimurium. Int J Food Microbiol115:307–312
    [Google Scholar]
  25. Choi C. H., Kim T. I., Lee S. K., Yang K. M., Kim W. H.. 2008; Effect of Lactobacillus GG and conditioned media on IL-1beta-induced IL-8 production in Caco-2 cells. Scand J Gastroenterol43:938–947
    [Google Scholar]
  26. Driessen A. J., Nouwen N.. 2008; Protein translocation across the bacterial cytoplasmic membrane. Annu Rev Biochem77:643–667
    [Google Scholar]
  27. Ewaschuk J. B., Díaz H., Meddings L., Diederichs B., Dmytrash A., Backer J., Looijer-van Langen M., Madsen K. L.. 2008; Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol295:G1025–G1034
    [Google Scholar]
  28. Favier C. F., de Vos W. M., Akkermans A. D.. 2003; Development of bacterial and bifidobacterial communities in feces of newborn babies. Anaerobe9:219–229
    [Google Scholar]
  29. Furrie E., Macfarlane S., Cummings J. H., Macfarlane G. T.. 2004; Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response. Gut53:91–98
    [Google Scholar]
  30. Gewirtz A. T.. 2006; Flag in the crossroads: flagellin modulates innate and adaptive immunity. Curr Opin Gastroenterol22:8–12
    [Google Scholar]
  31. Gill S. R., Pop M., Deboy R. T., Eckburg P. B., Turnbaugh P. J., Samuel B. S., Gordon J. I., Relman D. A., Fraser-Liggett C. M., Nelson K. E.. 2006; Metagenomic analysis of the human distal gut microbiome. Science312:1355–1359
    [Google Scholar]
  32. Grozdanov L., Raasch C., Schulze J., Sonnenborn U., Gottschalk G., Hacker J., Dobrindt U.. 2004; Analysis of the genome structure of the nonpathogenic probiotic Escherichia coli strain Nissle 1917. J Bacteriol186:5432–5441
    [Google Scholar]
  33. Gueimonde M., Ouwehand A., Huhtinen H., Salminen E., Salminen S.. 2007; Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease. World J Gastroenterol13:3985–3989
    [Google Scholar]
  34. Hoarau C., Martin L., Faugaret D., Baron C., Dauba A., Aubert-Jacquin C., Velge-Roussel F., Lebranchu Y.. 2008; Supernatant from Bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells. PLoS ONE3:e2753
    [Google Scholar]
  35. Hooper L. V., Gordon J. I.. 2001; Commensal host-bacterial relationships in the gut. Science292:1115–1118
    [Google Scholar]
  36. Hooper L. V., Wong M. H., Thelin A., Hansson L., Falk P. G., Gordon J. I.. 2001; Molecular analysis of commensal host-microbial relationships in the intestine. Science291:881–884
    [Google Scholar]
  37. Hurmalainen V., Edelman S., Antikainen J., Baumann M., Lahteenmaki K., Korhonen T. K.. 2007; Extracellular proteins of Lactobacillus crispatus enhance activation of human plasminogen. Microbiology153:1112–1122
    [Google Scholar]
  38. Iltanen S., Tervo L., Halttunen T., Wei B., Braun J., Rantala I., Honkanen T., Kronenberg M., Cheroutre H.. other authors 2006; Elevated serum anti-I2 and anti-OmpW antibody levels in children with IBD. Inflamm Bowel Dis12:389–394
    [Google Scholar]
  39. Ivanov D., Emonet C., Foata F., Affolter M., Delley M., Fisseha M., Blum-Sperisen S., Kochhar S., Arigoni F.. 2006; A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastase-like serine proteases. J Biol Chem281:17246–17252
    [Google Scholar]
  40. Ivison S. M., Steiner T. S.. 2008; Anti-flagellin antibodies in irritable bowel syndrome: another attack on our commensals?. Neurogastroenterol Motil20:1081–1085
    [Google Scholar]
  41. Iwamori M., Shibagaki T., Nakata Y., Adachi S., Nomura T.. 2009; Distribution of receptor glycolipids for lactobacilli in murine digestive tract and production of antibodies crossreactive with them by immunization of rabbits with lactobacilli. J Biochem146:185–191
    [Google Scholar]
  42. Jeffery C. J.. 2003; Moonlighting proteins: old proteins learning new tricks. Trends Genet19:415–417
    [Google Scholar]
  43. Jongbloed J. D., van der Ploeg R., van Dijl J. M.. 2006; Bifunctional TatA subunits in minimal Tat protein translocases. Trends Microbiol14:2–4
    [Google Scholar]
  44. Kankainen M., Paulin L., Tynkkynen S., von Ossowski I., Reunanen J., Partanen P., Satokari R., Vesterlund S., Hendrickx A. P.. other authors 2009; Comparative genomic analysis of Lactobacillus rhamnosus GG reveals pili containing a human- mucus binding protein. Proc Natl Acad Sci U S A106:17193–17198
    [Google Scholar]
  45. Kinoshita H., Uchida H., Kawai Y., Kawasaki T., Wakahara N., Matsuo H., Watanabe M., Kitazawa H., Ohnuma S.. & other authors (2008a). Cell surface Lactobacillus plantarum LA 318 glyceraldehyde-3-phosphate dehydrogenase (GAPDH) adheres to human colonic mucin. J Appl Microbiol104:1667–1674
    [Google Scholar]
  46. Kinoshita H., Wakahara N., Watanabe M., Kawasaki T., Matsuo H., Kawai Y., Kitazawa H., Ohnuma S., Miura K.. other authors 2008b; Cell surface glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of Lactobacillus plantarum LA 318 recognizes human A and B blood group antigens. Res Microbiol159:685–691
    [Google Scholar]
  47. Kleerebezem M., Hols P., Bernard E., Rolain T., Zhou M., Siezen R. J., Bron P. A.. 2010; The extracellular biology of the lactobacilli. FEMS Microbiol Rev34:199–230
    [Google Scholar]
  48. Konstantinov S. R., Smidt H., de Vos W. M., Bruijns S. C., Singh S. K., Valence F., Molle D., Lortal S., Altermann E.. other authors 2008; S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc Natl Acad Sci U S A105:19474–19479
    [Google Scholar]
  49. Kruis W., Fric P., Pokrotnieks J., Lukas M., Fixa B., Kascak M., Kamm M. A., Weismueller J., Beglinger C.. other authors 2004; Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut53:1617–1623
    [Google Scholar]
  50. Lasaro M. A., Salinger N., Zhang J., Wang Y., Zhong Z., Goulian M., Zhu J.. 2009; F1C fimbriae play an important role in biofilm formation and intestinal colonization by the Escherichia coli commensal strain Nissle 1917. Appl Environ Microbiol75:246–251
    [Google Scholar]
  51. Lebeer S., Ceuppens J., Geboes K., Van Assche G., Rutgeerts P., Vanderleyden J., De Keersmaecker S. C.. 2007a; Mechanisms of probiotic-host interaction with IBD as a case study: a role for exopolysaccharides?. Commun Agric Appl Biol Sci72:41–45
    [Google Scholar]
  52. Lebeer S., Verhoeven T. L., Perea V. M., Vanderleyden J., De Keersmaecker S. C.. 2007b; Impact of environmental and genetic factors on biofilm formation by the probiotic strain Lactobacillus rhamnosus GG. Appl Environ Microbiol73:6768–6775
    [Google Scholar]
  53. Lebeer S., Vanderleyden J., De Keersmaecker S. C.. 2008; Genes and molecules of lactobacilli supporting probiotic action. Microbiol Mol Biol Rev72:728–764
    [Google Scholar]
  54. Lebeer S., Vanderleyden J., De Keersmaecker S. C.. 2010; Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat Rev Microbiol8:171–184
    [Google Scholar]
  55. López P., Gueimonde M., Margolles A., Suarez A.. 2010; Distinct Bifidobacterium strains drive different immune responses in vitro. Int J Food Microbiol138:157–165
    [Google Scholar]
  56. Lu R., Fasano S., Madayiputhiya N., Morin N. P., Nataro J., Fasano A.. 2009; Isolation, identification, and characterization of small bioactive peptides from Lactobacillus GG conditional media that exert both anti-Gram-negative and Gram-positive bactericidal activity. J Pediatr Gastroenterol Nutr49:23–30
    [Google Scholar]
  57. Mitsuma T., Odajima H., Momiyama Z., Watanabe K., Masuguchi M., Sekine T., Shidara S., Hirano S.. 2008; Enhancement of gene expression by a peptide p(CHWPR) produced by Bifidobacterium lactis BB-12. Microbiol Immunol52:144–155
    [Google Scholar]
  58. Müller S., Schaffer T., Schoepfer A. M., Hilty A., Bodmer T., Seibold F.. 2008; Partial overlap of anti-mycobacterial, and anti- Saccharomyces cerevisiae mannan antibodies in Crohn's disease. World J Gastroenterol14:3650–3661
    [Google Scholar]
  59. Natale P., Bruser T., Driessen A. J.. 2008; Sec- and Tat-mediated protein secretion across the bacterial cytoplasmic membrane – distinct translocases and mechanisms. Biochim Biophys Acta 1778;1735–1756
    [Google Scholar]
  60. Pant A. R., Graham S. M., Allen S. J., Harikul S., Sabchareon A., Cuevas L., Hart C. A.. 1996; Lactobacillus GG and acute diarrhoea in young children in the tropics. J Trop Pediatr42:162–165
    [Google Scholar]
  61. Ramiah K., van Reenen C. A., Dicks L. M.. 2008; Surface-bound proteins of Lactobacillus plantarum 423 that contribute to adhesion of Caco-2 cells and their role in competitive exclusion and displacement of Clostridium sporogenes and Enterococcus faecalis. Res Microbiol159:470–475
    [Google Scholar]
  62. Ren T., Zamboni D. S., Roy C. R., Dietrich W. F., Vance R. E.. 2006; Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog2:e18
    [Google Scholar]
  63. Salminen S. J., Gueimonde M., Isolauri E.. 2005; Probiotics that modify disease risk. J Nutr135:1294–1298
    [Google Scholar]
  64. Salminen S., Collado M. C., Isolauri E., Gueimonde M.. 2009; Microbial-host interactions: selecting the right probiotics and prebiotics for infants. Nestle Nutr Workshop Ser Pediatr Program64:201–213
    [Google Scholar]
  65. Sánchez B., Bressollier P., Urdaci M. C.. 2008a; Exported proteins in probiotic bacteria: adhesion to intestinal surfaces, host immunomodulation and molecular cross-talking with the host. FEMS Immunol Med Microbiol54:1–17
    [Google Scholar]
  66. Sánchez B., Champomier-Vergès M. C., Anglade P., Baraige F., de los Reyes-Gavilan C. G., Margolles A., Zagorec M.. 2008b; A preliminary analysis of Bifidobacterium longum exported proteins by two-dimensional electrophoresis. J Mol Microbiol Biotechnol14:74–79
    [Google Scholar]
  67. Sánchez B., Arias S., Chaignepain S., Denayrolles M., Schmitter J. M., Bressollier P., Urdaci M. C.. 2009a; Identification of surface proteins involved in the adhesion of a probiotic Bacillus cereus strain to mucin and fibronectin. Microbiology155:1708–1716
    [Google Scholar]
  68. Sánchez B., Chaignepain S., Schmitter J. M., Urdaci M. C.. 2009b; A method for the identification of proteins secreted by lactic acid bacteria grown in complex media. FEMS Microbiol Lett295:226–229
    [Google Scholar]
  69. Sánchez B., Schmitter J. M., Urdaci M. C.. 2009c; Identification of novel proteins secreted by Lactobacillus plantarum that bind to mucin and fibronectin. J Mol Microbiol Biotechnol17:158–162
    [Google Scholar]
  70. Sánchez B., Schmitter J. M., Urdaci M. C.. 2009d; Identification of novel proteins secreted by Lactobacillus rhamnosus GG grown in de Man-Rogosa-Sharpe broth. Lett Appl Microbiol48:618–622
    [Google Scholar]
  71. Schlee M., Wehkamp J., Altenhoefer A., Oelschlaeger T. A., Stange E. F., Fellermann K.. 2007; Induction of human beta-defensin 2 by the probiotic Escherichia coli Nissle 1917 is mediated through flagellin. Infect Immun75:2399–2407
    [Google Scholar]
  72. Schlee M., Harder J., Köten B., Stange E. F., Wehkamp J., Fellermann K.. 2008; Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2. Clin Exp Immunol151:528–535
    [Google Scholar]
  73. Schoepfer A. M., Schaffer T., Seibold-Schmid B., Muller S., Seibold F.. 2008; Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients. Neurogastroenterol Motil20:1110–1118
    [Google Scholar]
  74. Seth A., Yan F., Polk D. B., Rao R. K.. 2008; Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism. Am J Physiol Gastrointest Liver Physiol294:G1060–G1069
    [Google Scholar]
  75. Sibbald M. J. J. B., van Dijl J. M.. 2009; Bacterial Secreted Proteins: Secretory Mechanisms and Role in Pathogenesis Edited by Wooldridge K.. Norwich, UK: Caister Academic Press. Horizon Scientific Press;
    [Google Scholar]
  76. Stappenbeck T. S., Hooper L. V., Gordon J. I.. 2002; Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A99:15451–15455
    [Google Scholar]
  77. Stringer C.. 2003; Human evolution: out of Ethiopia. Nature423:692–693
    [Google Scholar]
  78. Tao Y., Drabik K. A., Waypa T. S., Musch M. W., Alverdy J. C., Schneewind O., Chang E. B., Petrof E. O.. 2006; Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells. Am J Physiol Cell Physiol290:C1018–C1030
    [Google Scholar]
  79. Turnbaugh P. J., Ley R. E., Hamady M., Fraser-Liggett C. M., Knight R., Gordon J. I.. 2007; The human microbiome project. Nature449:804–810
    [Google Scholar]
  80. Turner M. S., Timms P., Hafner L. M., Giffard P. M.. 1997; Identification and characterization of a basic cell surface-located protein from Lactobacillus fermentum BR11. J Bacteriol179:3310–3316
    [Google Scholar]
  81. Turner M. S., Hafner L. M., Walsh T., Giffard P. M.. 2004; Identification and characterization of the novel LysM domain-containing surface protein Sep from Lactobacillus fermentum BR11 and its use as a peptide fusion partner in Lactobacillus and Lactococcus. Appl Environ Microbiol70:3673–3680
    [Google Scholar]
  82. Turroni F., Marchesi J. R., Foroni E., Gueimonde M., Shanahan F., Margolles A., van Sinderen D., Ventura M.. 2009; Microbiomic analysis of the bifidobacterial population in the human distal gut. ISME J3:745–751
    [Google Scholar]
  83. van Pijkeren J. P., Canchaya C., Ryan K. A., Li Y., Claesson M. J., Sheil B., Steidler L., O'Mahony L., Fitzgerald G. F.. other authors 2006; Comparative and functional analysis of sortase-dependent proteins in the predicted secretome of Lactobacillus salivarius UCC118. Appl Environ Microbiol72:4143–4153
    [Google Scholar]
  84. van Wely K. H. M., Swaving J., Freudl R., Driessen A. J. M.. 2001; Translocation of proteins across the cell envelope of Gram-positive bacteria. FEMS Microbiol Rev25:437–454
    [Google Scholar]
  85. Vélez M. P., De Keersmaecker S. C., Vanderleyden J.. 2007; Adherence factors of Lactobacillus in the human gastrointestinal tract. FEMS Microbiol Lett276:140–148
    [Google Scholar]
  86. von Heijne G.. 1989; The structure of signal peptides from bacterial lipoproteins. Protein Eng2:531–534
    [Google Scholar]
  87. von Heijne G., Abrahmsen L.. 1989; Species-specific variation in signal peptide design. Implications for protein secretion in foreign hosts. FEBS Lett244:439–446
    [Google Scholar]
  88. Willing B., Halfvarson J., Dicksved J., Rosenquist M., Järnerot G., Engstrand L., Tysk C., Jansson J. K.. 2009; Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm Bowel Dis15:653–660
    [Google Scholar]
  89. Yan F., Cao H., Cover T. L., Whitehead R., Washington M. K., Polk D. B.. 2007; Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology132:562–575
    [Google Scholar]
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