Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

The Impact of Gut Microbiota in Human Health and Diseases: Implication for Therapeutic Potential

  • Ha, Eun-Mi (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
  • Received : 2010.02.26
  • Accepted : 2011.04.22
  • Published : 2011.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Humans have and hold 100 trillion intestinal bacteria that are essential for health. For millions of years human-microorganisms interaction has co-evolved, and maintained close symbiotic relationship. Gut bacteria contributes to human health and metabolism, and humans provides the optimum nutrition-rich environment for bacteria. What is the mechanism of the host distinguishing the intestinal bacteria as its cohabiting partner and what kind of benefits does the gut microbiota provide the human are the fundamental questions to be asked and solved in order to make human life a higher quality. This review explains the physiological relationship and mutualism between the host and gut microorganism, and highlights the potential therapeutic approach for treating diseases, maintaining and improving health based on these correlations.

Keywords

References

  1. Abreu, M. T., Fukata M. and Arditi M. (2005) TLR signaling in the gut in health and disease. J. Immunol. 174, 4453-4460. https://doi.org/10.4049/jimmunol.174.8.4453
  2. Alcarraz-Vizan, G., Boren, J., Lee, W. N. and Cascante, M. (2010) Histone deacetylase inhibition results in a common metabolic profile associated with HT29 differentiation. Metabolomics. 6, 229-237. https://doi.org/10.1007/s11306-009-0192-0
  3. Allen, S. J., Okoko, B., Martinez, E., Gregorio, G. and Dans, L. F. (2004) Probiotics for treating infectious diarrhoea. Cochrane Database Syst. Rev. CD003048.
  4. Andersson, A. F., Lindberg, M., Jakobsson, H., Backhed, F., Nyren, P. and Engstrand, L. (2008) Comparative analysis of human gut microbiota by barcoded pyrosequencing. PLoS One. 3, e2836. https://doi.org/10.1371/journal.pone.0002836
  5. Armuzzi, A., Cremonini, F., Bartolozzi, F., Canducci, F., Candelli, M., Ojetti, V., Cammarota, G., Anti, M., De Lorenzo, A., Pola, P., Gasbarrini, G. and Gasbarrini, A. (2001a) The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy. Aliment Pharmacol. Ther. 15, 163-169. https://doi.org/10.1046/j.1365-2036.2001.00923.x
  6. Armuzzi, A., Cremonini, F., Ojetti, V., Bartolozzi, F., Canducci, F., Candelli, M., Santarelli, L., Cammarota, G., De Lorenzo, A., Pola, P., Gasbarrini, G. and Gasbarrini, A. (2001b) Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side effects during Helicobacter pylori eradication therapy: a pilot study. Digestion. 63, 1-7.
  7. Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., Cheng, G., Yamasaki, S., Saito, T., Ohba, Y., Taniguchi, T., Takeda, K., Hori, S., Ivanov, II, Umesaki, Y., Itoh, K. and Honda, K. (2011) Induction of colonic regulatory T cells by indigenous Clostridium species. Science 331, 337-341. https://doi.org/10.1126/science.1198469
  8. Backhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F. and Gordon, J. I. (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc. Natl. Acad. Sci. USA. 101, 15718-15723. https://doi.org/10.1073/pnas.0407076101
  9. Backhed, F., Manchester, J. K., Semenkovich, C. F. and Gordon, J. I. (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc. Natl. Acad. Sci. USA. 104, 979-984. https://doi.org/10.1073/pnas.0605374104
  10. Bae, Y. S., Choi, M. K. and Lee, W. J. (2010) Dual oxidase in mucosal immunity and host-microbe homeostasis. Trends Immunol. 31, 278-287. https://doi.org/10.1016/j.it.2010.05.003
  11. Baggio, L. L. and Drucker, D. J. (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology. 132, 2131-2157. https://doi.org/10.1053/j.gastro.2007.03.054
  12. Bakker-Zierikzee, A. M., Tol, E. A., Kroes, H., Alles, M. S., Kok, F. J. and Bindels, J. G. (2006) Faecal SIgA secretion in infants fed on pre- or probiotic infant formula. Pediatr. Allergy Immunol. 17, 134-140. https://doi.org/10.1111/j.1399-3038.2005.00370.x
  13. Bauer, H., Horowitz, R. E., Levenson, S. M. and Popper, H. (1963) The response of the lymphatic tissue to the microbial fl ora. Studies on germfree mice. Am. J. Pathol. 42, 471-483.
  14. Bibiloni, R., Fedorak, R. N., Tannock, G. W., Madsen, K. L., Gionchetti, P., Campieri, M., De Simone, C. and Sartor, R. B. (2005) VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am. J. Gastroenterol. 100, 1539-1546. https://doi.org/10.1111/j.1572-0241.2005.41794.x
  15. Bouhnik, Y., Raskine, L., Simoneau, G., Vicaut, E., Neut, C., Flourie, B., Brouns. F. and Bornet, F. R. (2004) The capacity of nondigestible carbohydrates to stimulate fecal bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, parallel-group, dose-response relation study. Am. J. Clin. Nutr. 80, 1658-1664.
  16. Bousvaros, A., Guandalini, S., Baldassano, R. N., Botelho, C. Evans, J., Ferry, G. D., Goldin, B., Hartigan, L., Kugathasan, S., Levy, J., Murray, K. F., Oliva-Hemker, M., Rosh, J. R., Tolia, V., Zholudev, A., Vanderhoof, J. A. and Hibberd, P. L. (2005) 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. 11, 833-839. https://doi.org/10.1097/01.MIB.0000175905.00212.2c
  17. Braat, H., de Jong, E. C., van den Brande, J. M., Kapsenberg, M. L., Peppelenbosch, M. P., van Tol, E. A. and van Deventer, S. J. (2004) Dichotomy between Lactobacillus rhamnosus and Klebsiella pneumoniae on dendritic cell phenotype and function. J. Mol. Med. 82, 197-205. https://doi.org/10.1007/s00109-003-0509-9
  18. Brandl, K., Plitas, G., Mihu, C. N., Ubeda, C., Jia, T., Fleisher, M., Schnabl, B., DeMatteo, R. P. and Pamer, E. G. (2008) Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature 455, 804-807. https://doi.org/10.1038/nature07250
  19. Breban, M. A., Moreau, M. C., Fournier, C., Ducluzeau, R. and Kahn, M. F. (1993) Influence of the bacterial flora on collagen-induced arthritis in susceptible and resistant strains of rats. Clin. Exp. Rheumatol. 11, 61-64.
  20. Brown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., Pike, N. B., Strum, J. C., Steplewski, K. M., Murdock, P. R., Holder, J. C., Marshall, F. H., Szekeres, P. G., Wilson, S., Ignar, D. M., Foord, S. M., Wise, A. and Dowell, S. J. (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem. 278, 11312-11319. https://doi.org/10.1074/jbc.M211609200
  21. Caballero, B. (2007) The global epidemic of obesity: an overview. Epidemiol. Rev. 29, 1-5. https://doi.org/10.1093/epirev/mxm012
  22. Candela, M., Seibold, G., Vitali, B., Lachenmaier, S., Eikmanns, B. J. and Brigidi, P. (2005) Real-time PCR quantification of bacterial adhesion to Caco-2 cells: competition between bifidobacteria and enteropathogens. Res. Microbiol. 156, 887-895. https://doi.org/10.1016/j.resmic.2005.04.006
  23. Canducci, F., Armuzzi, A., Cremonini, F., Cammarota, G., Bartolozzi, F., Pola, P., Gasbarrini. G. and Gasbarrini, A. (2000) A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates. Aliment. Pharmacol. Ther. 14, 1625-1629. https://doi.org/10.1046/j.1365-2036.2000.00885.x
  24. Cani, P. D., Daubioul, C. A., Reusens, B., Remacle, C., Catillon. G. and Delzenne, N. M. (2005) Involvement of endogenous glucagonlike peptide-1(7-36) amide on glycaemia-lowering effect of oligofructose in streptozotocin-treated rats. J. Endocrinol. 185, 457-465. https://doi.org/10.1677/joe.1.06100
  25. Cani, P. D. and Delzenne, N. M. (2007) Gut microfl ora as a target for energy and metabolic homeostasis. Curr. Opin. Clin. Nutr. Metab. Care 10, 729-734. https://doi.org/10.1097/MCO.0b013e3282efdebb
  26. Cani, P. D., Joly, E., Horsmans, Y. and Delzenne, N. M. (2006a) Oligofructose promotes satiety in healthy human: a pilot study. Eur. J. Clin. Nutr. 60, 567-572. https://doi.org/10.1038/sj.ejcn.1602350
  27. Cani, P. D., Knauf, C., Iglesias, M. A., Drucker, D. J., Delzenne, N. M. and Burcelin, R. (2006b) Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like peptide 1 receptor. Diabetes 55, 1484-1490. https://doi.org/10.2337/db05-1360
  28. Cani, P. D., Neyrinck, A. M., Fava, F., Knauf, C., Burcelin, R. G., Tuohy, K. M., Gibson, G. R. and Delzenne, N. M. (2007) Selective increases of bifidobacteria in gut microfl ora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 50, 2374-2383. https://doi.org/10.1007/s00125-007-0791-0
  29. Cario, E. and Podolsky, D. K. (2006) Toll-like receptor signaling and its relevance to intestinal inflammation. Ann. N Y Acad. Sci. 1072, 332-8. https://doi.org/10.1196/annals.1326.006
  30. Cash, H. L., Whitham, C. V., Behrendt, C. L. and Hooper, L. V. (2006) Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313, 1126-1130. https://doi.org/10.1126/science.1127119
  31. Cats, A., Kuipers, E. J., Bosschaert, M. A., Pot, R. G., Vandenbroucke-Grauls, C. M. and Kusters, J. G. (2003) Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects. Aliment Pharmacol. Ther. 17, 429-435. https://doi.org/10.1046/j.1365-2036.2003.01452.x
  32. Chichlowski, M. and Hale, L. P. (2008) Bacterial-mucosal interactions in infl ammatory bowel disease: an alliance gone bad. Am. J. Physiol. Gastrointest Liver Physiol. 295, G1139-1149. https://doi.org/10.1152/ajpgi.90516.2008
  33. Cindoruk, M., Erkan, G., Karakan, T., Dursun, A. and Unal, S. (2007) Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: a prospective randomized placebo-controlled double-blind study. Helicobacter 12, 309-316. https://doi.org/10.1111/j.1523-5378.2007.00516.x
  34. Claesson, M. J., O'Sullivan, O., Wang, Q., Nikkila, J., Marchesi, J. R., Smidt, H., de Vos, W. M., Ross, R. P. and O'Toole, P. W. (2009) Comparative analysis of pyrosequencing and a phylogenetic microarray for exploring microbial community structures in the human distal intestine. PLoS One. 4, e6669. https://doi.org/10.1371/journal.pone.0006669
  35. Collado, M. C., Hernandez, M. and Sanz, Y. (2005) Production of bacteriocin-like inhibitory compounds by human fecal Bifi dobacterium strains. J. Food Prot. 68, 1034-1040.
  36. Collado, M. C., Isolauri, E., Laitinen, K. and Salminen, S. (2008) Distinct composition of gut microbiota during pregnancy in overweight and normal-weight women. Am. J. Clin. Nutr. 88, 894-899.
  37. Collado, M. C., Meriluoto, J. and Salminen, S. (2007) Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus. Lett. Appl. Microbiol. 45, 454-460. https://doi.org/10.1111/j.1472-765X.2007.02212.x
  38. Conte, M. P., Schippa, S., Zamboni, I., Penta, M., Chiarini, F., Seganti, L., Osborn, J., Falconieri, P., Borrelli, O. and Cucchiara, S. (2006) Gut-associated bacterial microbiota in paediatric patients with infl ammatory bowel disease. Gut 55, 1760-1767. https://doi.org/10.1136/gut.2005.078824
  39. Corpeleijn, E., Saris, W. H. and Blaak, E. E. (2009) Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle. Obes. Rev. 10, 178-193. https://doi.org/10.1111/j.1467-789X.2008.00544.x
  40. Cotter, P. D., Hill, C. and Ross, R. P. (2005) Bacteriocins: developing innate immunity for food. Nat. Rev. Microbiol. 3, 777-788. https://doi.org/10.1038/nrmicro1273
  41. Cowie, C. C., Rust, K. F., Ford, E. S., Eberhardt, M. S., Byrd-Holt, D. D., Li, C., Williams, D. E., Gregg, E. W., Bainbridge, K. E., Saydah, S. H. and Geiss, L. S. (2009) Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006. Diabetes Care 32, 287-294. https://doi.org/10.2337/dc08-1296
  42. Creely, S. J., McTernan, P. G., Kusminski, C. M., Fisher, M., Da Silva, N. F., Khanolkar, M., Evans, M., Harte, A. L. and Kumar, S. (2007) Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 292, E740-747.
  43. Cremonini, F., Di Caro, S., Covino, M., Armuzzi, A., Gabrielli, M., Santarelli, L., Nista, E. C., Cammarota, G., Gasbarrini, G. and Gasbarrini, A. (2002a) Effect of different probiotic preparations on antihelicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am. J. Gastroenterol. 97, 2744-2749. https://doi.org/10.1111/j.1572-0241.2002.07063.x
  44. Cremonini, F., Di Caro, S., Nista, E. C., Bartolozzi, F., Capelli, G., Gasbarrini, G. and Gasbarrini, A. (2002b) Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea. Aliment Pharmacol. Ther. 16, 1461-1467. https://doi.org/10.1046/j.1365-2036.2002.01318.x
  45. Cruchet, S., Obregon, M. C., Salazar, G., Diaz, E. and Gotteland, M. (2003) Effect of the ingestion of a dietary product containing Lactobacillus johnsonii La1 on Helicobacter pylori colonization in children. Nutrition 19, 716-721. https://doi.org/10.1016/S0899-9007(03)00109-6
  46. D'Souza, A. L., Rajkumar, C., Cooke, J. and Bulpitt, C. J. (2002) Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis. BMJ 324, 1361. https://doi.org/10.1136/bmj.324.7350.1361
  47. Davis, C. P. and Savage, D. C. (1974) Habitat, succession, attachment, and morphology of segmented, filamentous microbes indigenous to the murine gastrointestinal tract. Infect. Immun. 10, 948-956.
  48. de Bortoli, N., Leonardi, G., Ciancia, E., Merlo, A., Bellini, M., Costa, F., Mumolo, M. G., Ricchiuti, A., Cristiani, F., Santi, S., Rossi, M. and Marchi, S. (2007) Helicobacter pylori eradication: a randomized prospective study of triple therapy versus triple therapy plus lactoferrin and probiotics. Am. J .Gastroenterol. 102, 951-956. https://doi.org/10.1111/j.1572-0241.2007.01085.x
  49. de Ruijter, A. J., van Gennip, A. H., Caron, H. N., Kemp, S. and van Kuilenburg, A. B. (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem. J. 370, 737-749. https://doi.org/10.1042/BJ20021321
  50. Dethlefsen, L., Huse, S., Sogin, M. L. and Relman, D. A. (2008) The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 6, e280. https://doi.org/10.1371/journal.pbio.0060280
  51. Drakes, M., Blanchard, T. and Czinn, S. (2004) Bacterial probiotic modulation of dendritic cells. Infect. Immun. 72, 3299-3309. https://doi.org/10.1128/IAI.72.6.3299-3309.2004
  52. Duncan, S. H., Lobley, G. E., Holtrop, G., Ince, J., Johnstone, A. M., Louis, P. and Flint, H. J. (2008) Human colonic microbiota associated with diet, obesity and weight loss. Int. J. Obes. (Lond). 32, 1720-1724. https://doi.org/10.1038/ijo.2008.155
  53. Edwards, C. J. and Cooper, C. (2006) Early environmental factors and rheumatoid arthritis. Clin. Exp. Immunol. 143, 1-5. https://doi.org/10.1111/j.1365-2249.2005.02940.x
  54. Felley, C. P., Corthesy-Theulaz, I., Rivero, J. L., Sipponen, P., Kaufmann, M., Bauerfeind, P., Wiesel, P. H., Brassart, D., Pfeifer, A. Blum, A. L. and Michetti, P. (2001) Favourable effect of an acidified milk (LC-1) on Helicobacter pylori gastritis in man. Eur. J. Gastroenterol. Hepatol. 13, 25-29. https://doi.org/10.1097/00042737-200101000-00005
  55. Flegal, K. M., Carroll, M. D., Ogden, C. L. and Curtin, L. R. (2010) Prevalence and trends in obesity among US adults, 1999-2008. JAMA 303, 235-241. https://doi.org/10.1001/jama.2009.2014
  56. Flint, H. J., Bayer, E. A., Rincon, M. T., Lamed, R. and White, B. A. (2008) Polysaccharide utilization by gut bacteria: potential for new insights from genomic analysis. Nat. Rev. Microbiol. 6, 121-131. https://doi.org/10.1038/nrmicro1817
  57. Fujimori, S., Tatsuguchi, A., Gudis, K., Kishida, T., Mitsui, K., Ehara, A., Kobayashi, T., Sekita, Y., Seo, T. and Sakamoto, C. (2007) High dose probiotic and prebiotic cotherapy for remission induction of active Crohn’s disease. J. Gastroenterol. Hepatol. 22, 1199-1204. https://doi.org/10.1111/j.1440-1746.2006.04535.x
  58. Furrie, E., Macfarlane, S., Kennedy, A., Cummings, J. H., Walsh, S. V., O'Neil, D. A. and Macfarlane, G. T. (2005) Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of infl ammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54, 242-249. https://doi.org/10.1136/gut.2004.044834
  59. Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T. and Ye, J. (2009) Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 58, 1509-1517. https://doi.org/10.2337/db08-1637
  60. Gibson, G. R. and Roberfroid, M. B. (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J. Nutr. 125, 1401-1412.
  61. Gionchetti, P., Rizzello, F., Helwig, U., Venturi, A., Lammers, K. M., Brigidi, P., Vitali, B., Poggioli, G., Miglioli, M. and Campieri, M. (2003) Prophylaxis of pouchitis onset with probiotic therapy: a doubleblind, placebo-controlled trial. Gastroenterology 124, 1202-1209. https://doi.org/10.1016/S0016-5085(03)00171-9
  62. Gionchetti, P., Rizzello, F., Venturi, A., Brigidi, P., Matteuzzi, D., Bazzocchi, G., Poggioli, G., Miglioli, M. and Campieri, M. (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119, 305-309. https://doi.org/10.1053/gast.2000.9370
  63. Goldsmith, M. E., Aguila, A., Steadman, K., Martinez, A., Steinberg, S. M., Alley, M. C., Waud, W. R., Bates, S. E. and Fojo, T. (2007) The histone deacetylase inhibitor FK228 given prior to adenovirus infection can boost infection in melanoma xenograft model systems. Mol. Cancer. Ther. 6, 496-505. https://doi.org/10.1158/1535-7163.MCT-06-0431
  64. Goossens, G. H. (2008) The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav. 94, 206-218. https://doi.org/10.1016/j.physbeh.2007.10.010
  65. Gosselink, M. P., Schouten, W. R. van Lieshout, L. M., Hop, W. C., Laman, J. D. and Ruseler-van Embden, J. G. (2004) Delay of the first onset of pouchitis by oral intake of the probiotic strain Lactobacillus rhamnosus GG. Dis. Colon. Rectum. 47, 876-884. https://doi.org/10.1007/s10350-004-0525-z
  66. Griffiths, E. A., Duffy, L. C., Schanbacher, F. L., Qiao, H., Dryja, D., Leavens, A., Rossman, J., Rich, G., Dirienzo, D. and Ogra, P. L. (2004) In vivo effects of bifidobacteria and lactoferrin on gut endotoxin concentration and mucosal immunity in Balb/c mice. Dig. Dis. Sci. 49, 579-589. https://doi.org/10.1023/B:DDAS.0000026302.92898.ae
  67. Guslandi, M., Giollo, P. and Testoni, P. A. (2003) A pilot trial of Saccharomyces boulardii in ulcerative colitis. Eur. J. Gastroenterol. Hepatol. 15, 697-698. https://doi.org/10.1097/00042737-200306000-00017
  68. Ha, E. M., Lee, K. A., Seo, Y. Y., Kim, S. H., Lim, J. H., Oh, B. H., Kim, J. and Lee, W. J. (2009) Coordination of multiple dual oxidaseregulatory pathways in responses to commensal and infectious microbes in drosophila gut. Nat. Immunol. 10, 949-957. https://doi.org/10.1038/ni.1765
  69. Ha, E. M., Oh, C. T., Bae, Y. S. and Lee, W. J. (2005) A direct role for dual oxidase in Drosophila gut immunity. Science 310, 847-850. https://doi.org/10.1126/science.1117311
  70. Hajjar, A. M., Ernst, R. K., Tsai, J. H., Wilson, C. B. and Miller, S. I. (2002) Human Toll-like receptor 4 recognizes host-specific LPS modifi cations. Nat. Immunol. 3, 354-359. https://doi.org/10.1038/ni777
  71. Hart, A. L., Lammers, K., Brigidi, P., Vitali, B., Rizzello, F., Gionchetti, P., Campieri, M., Kamm, M. A., Knight, S. C. and Stagg, A. J. (2004) Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut 53, 1602-1609. https://doi.org/10.1136/gut.2003.037325
  72. Hawrelak, J. A., Whitten, D. L. and Myers, S. P. (2005) Is Lactobacillus rhamnosus GG effective in preventing the onset of antibiotic-associated diarrhoea: a systematic review. Digestion 72, 51-56. https://doi.org/10.1159/000087637
  73. He, F., Morita, H., Kubota, A., Ouwehand, A. C., Hosoda, M., Hiramatsu, M. and Kurisaki, J. (2005) Effect of orally administered nonviable Lactobacillus cells on murine humoral immune responses. Microbiol. Immunol. 49, 993-997. https://doi.org/10.1111/j.1348-0421.2005.tb03695.x
  74. Heerdt, B. G., Houston, M. A. and Augenlicht, L. H. (1994) Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines. Cancer Res. 54, 3288-3293.
  75. Hickson, M., D'Souza, A. L., Muthu, N., Rogers, T. R., Want, S., Rajkumar, C. and Bulpitt. C. J. (2007) Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 335, 80. https://doi.org/10.1136/bmj.39231.599815.55
  76. Hill, J. A., Hall, J. A., Sun, C. M., Cai, Q., Ghyselinck, N., Chambon, P., Belkaid, Y., Mathis, D. and Benoist, C. (2008) Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells. Immunity 29, 758-770. https://doi.org/10.1016/j.immuni.2008.09.018
  77. Hooper, L. V. and Gordon, J. I. (2001) Commensal host-bacterial relationships in the gut. Science 292, 1115-1118. https://doi.org/10.1126/science.1058709
  78. Hooper, L. V. and Macpherson, A. J. (2010) Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10, 159-169. https://doi.org/10.1038/nri2710
  79. Hooper, L. V., Stappenbeck, T. S., Hong, C. V. and Gordon, J. I. (2003) Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat. Immunol. 4, 269-273. https://doi.org/10.1038/ni888
  80. Hotamisligil, G. S. (2006) Inflammation and metabolic disorders. Nature 444, 860-867. https://doi.org/10.1038/nature05485
  81. Huang, J. S., Bousvaros, A., Lee, J. W., Diaz, A. and Davidson, E. J. (2002) Efficacy of probiotic use in acute diarrhea in children: a meta-analysis. Dig. Dis. Sci. 47, 2625-2634. https://doi.org/10.1023/A:1020501202369
  82. Ishikawa, H., Akedo, I., Umesaki, Y., Tanaka, R., Imaoka, A. and Otani, T. (2003) Randomized controlled trial of the effect of bifidobacteriafermented milk on ulcerative colitis. J. Am. Coll. Nutr. 22, 56-63. https://doi.org/10.1080/07315724.2003.10719276
  83. Ivanov, II, Atarashi, K., Manel, N., Brodie, E. L., Shima, T., Karaoz, U., Wei, D., Goldfarb, K. C., Santee, C. A., Lynch, S. V., Tanoue, T., Imaoka, A., Itoh, K., Takeda, K., Umesaki, Y., Honda, K. and Littman, D. R. (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139, 485-498. https://doi.org/10.1016/j.cell.2009.09.033
  84. Jia, W., Li, H., Zhao, L. and Nicholson, J. K. (2008) Gut microbiota: a potential new territory for drug targeting. Nat. Rev. Drug Discov. 7, 123-9. https://doi.org/10.1038/nrd2505
  85. Jijon, H., Backer, J., Diaz, H., Yeung, H., Thiel, D., McKaigney, C., De Simone, C. and Madsen, K. (2004) DNA from probiotic bacteria modulates murine and human epithelial and immune function. Gastroenterology 126, 1358-1373. https://doi.org/10.1053/j.gastro.2004.02.003
  86. Johnston, B. C., Supina, A. L., Ospina, M. and Vohra, S. (2007) Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst. Rev. CD004827.
  87. Johnston, B. C., Supina, A. L. and Vohra, S. (2006) Probiotics for pediatric antibiotic-associated diarrhea: a meta-analysis of randomized placebo-controlled trials. CMAJ 175, 377-383. https://doi.org/10.1503/cmaj.051603
  88. Kalliomaki, M., Collado, M. C. Salminen, S. and Isolauri, E. (2008) Early differences in fecal microbiota composition in children may predict overweight. Am. J. Clin. Nutr. 87, 534-538.
  89. Karaki, S., Mitsui, R., Hayashi, H., Kato, I., Sugiya, H., Iwanaga, T., Furness, J. B. and Kuwahara, A. (2006) Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res. 324, 353-360. https://doi.org/10.1007/s00441-005-0140-x
  90. Karvonen, M., Tuomilehto, J., Libman, I. and LaPorte, R. (1993) A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. World Health Organization DIAMOND Project Group. Diabetologia 36, 883-892. https://doi.org/10.1007/BF02374468
  91. Kato, K., Mizuno, S., Umesaki, Y., Ishii, Y., Sugitani, M., Imaoka, A., Otsuka, M., Hasunuma, O., Kurihara, R., Iwasaki, A. and Arakawa, Y. (2004) Randomized placebo-controlled trial assessing the effect of bifi dobacteria-fermented milk on active ulcerative colitis. Aliment Pharmacol. Ther. 20, 1133-1141. https://doi.org/10.1111/j.1365-2036.2004.02268.x
  92. Kim, S. O., Sheikh, H. I., Ha, S. D., Martins, A. and Reid, G. (2006) G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages. Cell Microbiol. 8, 1958-1971. https://doi.org/10.1111/j.1462-5822.2006.00763.x
  93. Klaasen, H. L., Koopman, J. P., Van den Brink, M. E., Bakker, M. H. Poelma, F. G. and Beynen, A. C. (1993) Intestinal, segmented, filamentous bacteria in a wide range of vertebrate species. Lab. Anim. 27, 141-150. https://doi.org/10.1258/002367793780810441
  94. Knight, P., Campbell, B. J. and Rhodes, J. M. (2008) Host-bacteria interaction in inflammatory bowel disease. Br. Med. Bull. 88, 95-113. https://doi.org/10.1093/bmb/ldn038
  95. Kok, N. N., Morgan, L. M., Williams, C. M., Roberfroid, M. B., Thissen, J. P. and Delzenne, N. M. (1998) Insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide and insulin-like growth factor I as putative mediators of the hypolipidemic effect of oligofructose in rats. J. Nutr. 128, 1099-1103.
  96. Kolida, S., Meyer, D. and Gibson, G. R. (2007) A double-blind placebocontrolled study to establish the bifi dogenic dose of inulin in healthy humans. Eur. J. Clin. Nutr. 61, 1189-1195. https://doi.org/10.1038/sj.ejcn.1602636
  97. Kraehenbuhl, J. P. and Corbett, M. (2004) Immunology. Keeping the gut microfl ora at bay. Science 303, 1624-1625. https://doi.org/10.1126/science.1096222
  98. Krieg, A. M. (2003) CpG motifs: the active ingredient in bacterial extracts? Nat. Med. 9, 831-835. https://doi.org/10.1038/nm0703-831
  99. Kruis, W., Fric, P., Pokrotnieks, J., Lukas, M., Fixa, B., Kascak, M., Kamm, M. A., Weismueller, J., Beglinger, C., Stolte, M., Wolff, C. and Schulze, J. (2004) Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut 53, 1617-1623. https://doi.org/10.1136/gut.2003.037747
  100. Kruis, W., Schutz, E., Fric, P., Fixa, B., Judmaier, G. and Stolte, M. (1997) Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol. Ther. 11, 853-858. https://doi.org/10.1046/j.1365-2036.1997.00225.x
  101. Laake, K. O., Bjorneklett, A., Aamodt, G., Aabakken, L., Jacobsen, M., Bakka, A. and Vatn, M. H. (2005) Outcome of four weeks' intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-analanastomosis in ulcerative colitis. Scand. J. Gastroenterol. 40, 43-51. https://doi.org/10.1080/00365520410009339
  102. Larsen, N., Vogensen, F. K., van den Berg, F. W., Nielsen, D. S. Andreasen, A. S., Pedersen, B. K., Al-Soud, W. A., Sorensen, S. J., Hansen, L. H. and Jakobsen M. (2010) Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 5, e9085. https://doi.org/10.1371/journal.pone.0009085
  103. Lawton, E. M., Ross, R. P., Hill, C. and Cotter, P. D. (2007) Two-peptide lantibiotics: a medical perspective. Mini. Rev. Med. Chem. 7, 1236-1247. https://doi.org/10.2174/138955707782795638
  104. Lebeer, S., Vanderleyden, J. and De Keersmaecker, S. C. (2010) Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat. Rev. Microbiol. 8, 171-184. https://doi.org/10.1038/nrmicro2297
  105. Lee, J., Mo, J. H., Katakura, K., Alkalay, I., Rucker, A. N., Liu, Y. T., Lee, H. K., Shen, C., Cojocaru, G., Shenouda, S., Kagnoff, M., Eckmann, L., Ben-Neriah, Y. and Raz, E. (2006) Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat. Cell Biol. 8, 1327-1336. https://doi.org/10.1038/ncb1500
  106. Le Poul, E., Loison, C., Struyf, S., Springael, J. Y., Lannoy, V., Decobecq, M. E., Brezillon, S., Dupriez, V., Vassart, G., Van Damme, J., Parmentier, M. and Detheux, M. (2003) Functional characterization of human receptors for short chain fatty acids and their role in poly morphonuclear cell activation. J. Biol. Chem. 278, 25481-25489. https://doi.org/10.1074/jbc.M301403200
  107. Levison, M. E. (1973) Effect of colon flora and short-chain fatty acids on growth in vitro of Pseudomonas aeruginsoa and Enterobacteriaceae. Infect. Immun. 8, 30-35.
  108. Ley, R. E., Backhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D. and Gordon, J. I. (2005) Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 102, 11070-11075. https://doi.org/10.1073/pnas.0504978102
  109. Ley, R. E., Turnbaugh, P. J., Klein, S. and Gordon, J. I. (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022-1023. https://doi.org/10.1038/4441022a
  110. Lichtenberger, G. S., Flavell, R. A. and Alexopoulou, L. (2004) Innate immunity and apoptosis in IBD. Inflamm. Bowel Dis. 10(Suppl 1), S58-62. https://doi.org/10.1097/00054725-200402001-00012
  111. Lionetti, E., Miniello, V. L., Castellaneta, S. P., Magista, A. M., de Canio, A., Maurogiovanni, G., Ierardi, E., Cavallo, L. and Francavilla, R. (2006) Lactobacillus reuteri therapy to reduce side-effects during anti-Helicobacter pylori treatment in children: a randomized placebo controlled trial. Aliment Pharmacol. Ther. 24, 1461-1468. https://doi.org/10.1111/j.1365-2036.2006.03145.x
  112. Litvak, D. A., Evers, B. M., Hwang, K. O., Hellmich, M. R., Ko, T. C. and Townsend, C. M. Jr. (1998) Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21Waf1/Cip1 and p27Kip1. Surgery 124, 161-169; discussion 169-70. https://doi.org/10.1016/S0039-6060(98)70116-3
  113. Lodinova-Zadnikova, R., Cukrowska, B. and Tlaskalova-Hogenova, H. (2003) Oral administration of probiotic Escherichia coli after birth reduces frequency of allergies and repeated infections later in life (after 10 and 20 years). Int. Arch. Allergy Immunol. 131, 209-211. https://doi.org/10.1159/000071488
  114. Lugering, A., Lebiedz, P., Koch, S. and Kucharzik, T. (2006) Apoptosis as a therapeutic tool in IBD? Ann. N Y Acad. Sci. 1072, 62-77. https://doi.org/10.1196/annals.1326.013
  115. Macfarlane, S., Macfarlane, G. T. and Cummings, J. H. (2006) Review article: prebiotics in the gastrointestinal tract. Aliment Pharmacol. Ther. 24, 701-714. https://doi.org/10.1111/j.1365-2036.2006.03042.x
  116. Macpherson, A. J. and Uhr, T. (2004) Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303, 1662-1625. https://doi.org/10.1126/science.1091334
  117. Malchow, H. A. (1997) Crohn’s disease and Escherichia coli. A new approach in therapy to maintain remission of colonic Crohn’s disease? J. Clin.Gastro-enterol. 25, 653-658. https://doi.org/10.1097/00004836-199712000-00021
  118. Makras, L., Triantafyllou, V., Fayol-Messaoudi, D., Adriany, T., Zoumpopoulou, G., Tsakalidou, E., Servin, A. and De Vuyst, L. (2006) Kinetic analysis of the antibacterial activity of probiotic lactobacilli towards Salmonella enterica serovar Typhimurium reveals a role for lactic acid and other inhibitory compounds. Res. Microbiol. 157, 241-247. https://doi.org/10.1016/j.resmic.2005.09.002
  119. Mariadason, J. M. (2008) HDACs and HDAC inhibitors in colon cancer. Epigenetics 3, 28-37. https://doi.org/10.4161/epi.3.1.5736
  120. Marks, P. A. and Xu, W. S. (2009) Histone deacetylase inhibitors: Potential in cancer therapy. J. Cell Biochem. 107, 600-608. https://doi.org/10.1002/jcb.22185
  121. Marteau, P., Lemann, M., Seksik, P., Laharie, D., Colombel, J. F., Bouhnik, Y., Cadiot, J. C., Soule, G., Bourreille, A., Metman, E., Lerebours, E., Carbonnel, F., Dupas, J. L., Veyrac, M., Coffi n, B., Moreau, J., Abitbol, V., Blum-Sperisen, S. and Mary, J. Y. (2006) Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial. Gut 55, 842-847. https://doi.org/10.1136/gut.2005.076604
  122. Matsumoto, S., Hara, T., Hori, T., Mitsuyama, K., Nagaoka, M., Tomiyasu, N., Suzuki. A. and Sata, M. (2005) Probiotic Lactobacillusinduced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines in lamina propria mononuclear cells. Clin. Exp. Immunol. 140, 417-426. https://doi.org/10.1111/j.1365-2249.2005.02790.x
  123. Mazmanian, S. K., Liu, C. H., Tzianabos, A. O. and Kasper, D. L. (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122, 107-118. https://doi.org/10.1016/j.cell.2005.05.007
  124. McCool, D. J., Forstner, J. F. and Forstner, G. G. (1994) Synthesis and secretion of mucin by the human colonic tumour cell line LS180. Biochem. J. 302(Pt 1), 111-118.
  125. McFarland, L. V. (2006) Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am. J. Gastroenterol. 101, 812-822. https://doi.org/10.1111/j.1572-0241.2006.00465.x
  126. Michetti, P., Dorta, G., Wiesel, P. H., Brassart, D., Verdu, E., Herranz, M., Felley, C., Porta, N., Rouvet, M., Blum, A. L. and Corthesy-Theulaz, I. (1999) Effect of whey-based culture supernatant of Lactobacillus acidophilus (johnsonii) La1 on Helicobacter pylori infection in humans. Digestion 60, 203-209. https://doi.org/10.1159/000007660
  127. Mimura, T., Rizzello, F., Helwig, U., Poggioli, G., Schreiber, S. Talbot, I. C., Nicholls, R. J., Gionchetti, P, Campieri, M. and Kamm, M. A. (2004) Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 53, 108-114. https://doi.org/10.1136/gut.53.1.108
  128. Mohamadzadeh, M., Olson, S., Kalina, W. V., Ruthel, G., Demmin, G. L., Warfield, K. L., Bavari, S. and Klaenhammer, T. R. (2005) Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization. Proc. Natl. Acad. Sci. USA. 102, 2880-2885. https://doi.org/10.1073/pnas.0500098102
  129. Morgan, S. M., O'Connor, P. M., Cotter, P. D., Ross, R. P. and Hill, C. (2005) Sequential actions of the two component peptides of the lantibiotic lacticin 3147 explain its antimicrobial activity at nanomolar concentrations. Antimicrob. Agents Chemother. 49, 2606-2611. https://doi.org/10.1128/AAC.49.7.2606-2611.2005
  130. Mukai, T., Kaneko, S., Matsumoto, M. and Ohori, H. (2004) Binding of Bifidobacterium bifidum and Lactobacillus reuteri to the carbohydrate moieties of intestinal glycolipids recognized by peanut agglutinin. Int. J. Food Microbiol. 90, 357-362. https://doi.org/10.1016/S0168-1605(03)00317-9
  131. Murphy, K. G., Dhillo, W. S. and Bloom, S. R. (2006) Gut peptides in the regulation of food intake and energy homeostasis. Endocr. Rev. 27, 719-727. https://doi.org/10.1210/er.2006-0028
  132. Myllyluoma, E., Veijola, L., Ahlroos, T., Tynkkynen, S., Kankuri, E., Vapaatalo, H., Rautelin, H. and Korpela, R. (2005) Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy--a placebo-controlled, double-blind randomized pilot study. Aliment Pharmacol. Ther. 21, 1263-1272. https://doi.org/10.1111/j.1365-2036.2005.02448.x
  133. Mylonaki, M., Rayment, N. B., Rampton, D. S., Hudspith, B. N. and Brostoff, J. (2005) Molecular characterization of rectal mucosaassociated bacterial fl ora in inflammatory bowel disease. Inflamm. Bowel Dis. 11, 481-487. https://doi.org/10.1097/01.MIB.0000159663.62651.4f
  134. Nadal, I., Santacruz, A., Marcos, A., Warnberg, J., Garagorri, M., Moreno, L. A., Martin-Matillas, M., Campoy, C., Marti, A., Moleres, A., Delgado, M., Veiga, O. L., Garcia-Fuentes, M., Redondo, C. G. and Sanz, Y. (2009) Shifts in clostridia, bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int. J. Obes (Lond). 33, 758-767. https://doi.org/10.1038/ijo.2008.260
  135. Neal, M. D., Leaphart, C., Levy, R., Prince, J., Billiar, T. R., Watkins, S. Li, J., Cetin, S., Ford, H., Schreiber, A. and Hackam, D. J. (2006) Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J. Immunol. 176, 3070-3079. https://doi.org/10.4049/jimmunol.176.5.3070
  136. Neish, A. S. (2009) Microbes in gastrointestinal health and disease. Gastroenterology. 136, 65-80. https://doi.org/10.1053/j.gastro.2008.10.080
  137. Nicholson, J. K., Holmes, E. and Wilson, I. D. (2005) Gut microorganisms, mammalian metabolism and personalized health care. Nat. Rev. Microbiol. 3, 431-438. https://doi.org/10.1038/nrmicro1152
  138. Noverr, M. C. and Huffnagle, G. B. (2004) Does the microbiota regulate immune responses outside the gut? Trends Microbiol. 12, 562-568. https://doi.org/10.1016/j.tim.2004.10.008
  139. Noverr, M. C. and Huffnagle, G. B. (2005) The 'microflora hypothesis' of allergic diseases. Clin. Exp. Allergy 35, 1511-1520. https://doi.org/10.1111/j.1365-2222.2005.02379.x
  140. Ohwaki, M., Yasutake, N., Yasui, H. and Ogura, R. (1977) A comparative study on the humoral immune responses in germ-free and conventional mice. Immunology 32, 43-48.
  141. Ott, S. J., Musfeldt, M., Wenderoth, D. F., Hampe, J., Brant, O., Folsch, U. R., Timmis, K. N. and Schreiber, S. (2004) Reduction in diversity of the colonic mucosa associated bacterial microfl ora in patients with active inflammatory bowel disease. Gut 53, 685-693. https://doi.org/10.1136/gut.2003.025403
  142. Otte, J. M. and Podolsky, D. K. (2004) Functional modulation of enterocytes by gram-positive and gram-negative microorganisms. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G613-626. https://doi.org/10.1152/ajpgi.00341.2003
  143. Palmer, C., Bik, E. M., DiGiulio, D. B., Relman, D. A. and Brown, P. O. (2007) Development of the human infant intestinal microbiota. PLoS Biol. 5, e177. https://doi.org/10.1371/journal.pbio.0050177
  144. Pappo, I., Becovier, H., Berry, E. M. and Freund, H. R. (1991) Polymyxin B reduces cecal flora, TNF production and hepatic steatosis during total parenteral nutrition in the rat. J. Surg. Res. 51, 106-112. https://doi.org/10.1016/0022-4804(91)90078-Z
  145. Parassol, N., Freitas, M., Thoreux, K., Dalmasso, G., Bourdet-Sicard, R. and Rampal, P. (2005) Lactobacillus casei DN-114 001 inhibits the increase in paracellular permeability of enteropathogenic Escherichia coli-infected T84 cells. Res. Microbiol. 156, 256-262. https://doi.org/10.1016/j.resmic.2004.09.013
  146. Parnell, J. A. and Reimer, R. A. (2009) Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am. J. Clin. Nutr. 89, 1751-1759. https://doi.org/10.3945/ajcn.2009.27465
  147. Patterson, C. C., Dahlquist, G., Soltesz, G. and Green, A. (2001) Is childhood-onset type I diabetes a wealth-related disease? An ecological analysis of European incidence rates. Diabetologia 44(Suppl 3), B9-16. https://doi.org/10.1007/PL00002961
  148. Pena, J. A. and Versalovic, J. (2003) Lactobacillus rhamnosus GG decreases TNF-alpha production in lipopolysaccharide-activated murine macrophages by a contact-independent mechanism. Cell Microbiol. 5, 277-285. https://doi.org/10.1046/j.1462-5822.2003.t01-1-00275.x
  149. Perrine, S. P., Hermine, O., Small, T., Suarez, F., O'Reilly, R., Boulad, F., Fingeroth, J., Askin, M., Levy, A., Mentzer, S. J., Di Nicola, M., Gianni, A. M., Klein, C., Horwitz, S. and Faller, D. V. (2007) A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 109, 2571-2578. https://doi.org/10.1182/blood-2006-01-024703
  150. Prantera, C., Scribano, M. L., Falasco, G., Andreoli, A. and Luzi, C. (2002) Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG. Gut. 51, 405-409. https://doi.org/10.1136/gut.51.3.405
  151. Pronio, A., Montesani, C., Butteroni, C., Vecchione, S., Mumolo, G., Vestri, A., Vitolo, D. and Boirivant, M. (2008) Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm. Bowel Dis. 14, 662-668. https://doi.org/10.1002/ibd.20369
  152. Rachmilewitz, D., Katakura, K., Karmeli, F., Hayashi, T., Reinus, C., Rudensky, B., Akira, S., Takeda, K., Lee, J., Takabayashi, K. and Raz. E. (2004) Toll-like receptor 9 signaling mediates the antiinfl ammatory effects of probiotics in murine experimental colitis. Gastroenterology. 126, 520-528. https://doi.org/10.1053/j.gastro.2003.11.019
  153. Rajilic-Stojanovic, M., Maathuis, A., Heilig, H. G., Venema, K., de Vos, W. M. and Smidt, H. (2010) Evaluating the microbial diversity of an in vitro model of the human large intestine by phylogenetic microarray analysis. Microbiology. 156, 3270-3281. https://doi.org/10.1099/mic.0.042044-0
  154. Rembacken, B. J., Snelling, A. M., Hawkey, P. M., Chalmers, D. M. and Axon, A. T. (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet. 354, 635-639. https://doi.org/10.1016/S0140-6736(98)06343-0
  155. Resta-Lenert, S. and Barrett, K. E. (2006) Probiotics and commensals reverse TNF-alpha- and IFN-gamma-induced dysfunction in human intestinal epithelial cells. Gastroenterology 130, 731-746. https://doi.org/10.1053/j.gastro.2005.12.015
  156. Rhee, S. H., Pothoulakis, C. and Mayer, E. A. (2009) Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat. Rev. Gastroenterol. Hepatol. 6, 306-314. https://doi.org/10.1038/nrgastro.2009.35
  157. Roselli, M., Finamore, A., Britti, M. S. and Mengheri, E. (2006) Probiotic bacteria Bifidobacterium animalis MB5 and Lactobacillus rhamnosus GG protect intestinal Caco-2 cells from the inflammationassociated response induced by enterotoxigenic Escherichia coli K88. Br. J. Nutr. 95, 1177-1184. https://doi.org/10.1079/BJN20051681
  158. Round, J. L. and Mazmanian, S. K. (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313-323. https://doi.org/10.1038/nri2515
  159. Ruszczynski, M., Radzikowski, A. and Szajewska, H. (2008) Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment Pharmacol. Ther. 28, 154-161. https://doi.org/10.1111/j.1365-2036.2008.03714.x
  160. Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M. and Gordon, J. I. (2008) Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. USA. 105, 16767-16772. https://doi.org/10.1073/pnas.0808567105
  161. Sanders, M. E. (2003) Probiotics: considerations for human health. Nutr. Rev. 61, 91-99. https://doi.org/10.1301/nr.2003.marr.91-99
  162. Sazawal, S., Hiremath, G., Dhingra, U., Malik, P., Deb, S. and Black, R. E. (2006) Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet. Infect. Dis. 6, 374-382. https://doi.org/10.1016/S1473-3099(06)70495-9
  163. Schlee, M., Harder, J., Koten, B., Stange, E. F., Wehkamp, J. and Fellermann. K. (2008) Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2. Clin. Exp. Immunol. 151, 528-535. https://doi.org/10.1111/j.1365-2249.2007.03587.x
  164. Schlee, M., Wehkamp, J., Altenhoefer, A., Oelschlaeger, T. A., Stange, E. F. and Fellermann, K. (2007) Induction of human beta-defensin 2 by the probiotic Escherichia coli Nissle 1917 is mediated through flagellin. Infect. Immun. 75, 2399-2407. https://doi.org/10.1128/IAI.01563-06
  165. Schultz, M., Timmer, A., Herfarth, H. H., Sartor, R. B., Vanderhoof, J. A. and Rath, H. C. (2004) Lactobacillus GG in inducing and maintaining remission of Crohn's disease. BMC Gastroenterol. 4, 5. https://doi.org/10.1186/1471-230X-4-5
  166. Servin, A. L. (2004) Antagonistic activities of lactobacilli and bifi dobacteria against microbial pathogens. FEMS Microbiol. Rev. 28, 405-440. https://doi.org/10.1016/j.femsre.2004.01.003
  167. Seth, A., Yan, F., Polk, D. B. and 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 Physiol. 294, G1060-1069. https://doi.org/10.1152/ajpgi.00202.2007
  168. Sherman, P. M., Johnson-Henry, K. C., Yeung, H. P., Ngo, P. S., Goulet, J. and Tompkins, T. A. (2005) Probiotics reduce enterohemorrhagic Escherichia coli O157:H7- and enteropathogenic E. coli O127:H6-induced changes in polarized T84 epithelial cell monolayers by reducing bacterial adhesion and cytoskeletal rearrangements. Infect. Immun. 73, 5183-5188. https://doi.org/10.1128/IAI.73.8.5183-5188.2005
  169. Sheu, B. S., Cheng, H. C., Kao, A. W., Wang, S. T., Yang, Y. J., Yang, H. B. and Wu, J. J. (2006) Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can improve the effi cacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy. Am. J. Clin. Nutr. 83, 864-869.
  170. Smith, K., McCoy, K. D. and Macpherson, A. J. (2007) Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin. Immunol. 19, 59-69. https://doi.org/10.1016/j.smim.2006.10.002
  171. Smits, H. H., Engering, A., van der Kleij, D., de Jong, E. C., Schipper, K., van Capel, T. M., Zaat, B. A., Yazdanbakhsh, M., Wierenga, E. A., van Kooyk, Y. and Kapsenberg, M. L. (2005) Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J. Allergy Clin. Immunol. 115, 1260-1267. https://doi.org/10.1016/j.jaci.2005.03.036
  172. Soo, I., Madsen, K. L., Tejpar, Q., Sydora, B. C., Sherbaniuk, R., Cinque, B., Di Marzio, L., Cifone, M. G., Desimone, C. and Fedorak, R. N. (2008) VSL#3 probiotic upregulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation. Can. J. Gastroenterol. 22, 237-242.
  173. Strachan, D. P. (1989) Hay fever, hygiene, and household size. BMJ 299, 1259-1260. https://doi.org/10.1136/bmj.299.6710.1259
  174. Strober, W., Fuss, I. and Mannon, P. (2007) The fundamental basis of inflammatory bowel disease. J. Clin. Invest. 117, 514-521. https://doi.org/10.1172/JCI30587
  175. Sturm, A., Rilling, K., Baumgart, D. C., Gargas, K., Abou-Ghazale, T., Raupach, B., Eckert, J., Schumann, R. R., Enders, C., Sonnenborn, U., Wiedenmann, B. and Dignass, A. U. (2005) Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling. Infect. Immun. 73, 1452-1465. https://doi.org/10.1128/IAI.73.3.1452-1465.2005
  176. Sun, J., Le, G. W., Shi, Y. H. and Su, G. W. (2007) Factors involved in binding of Lactobacillus plantarum Lp6 to rat small intestinal mucus. Lett. Appl. Microbiol. 44, 79-85. https://doi.org/10.1111/j.1472-765X.2006.02031.x
  177. Sykora, J., Valeckova, K., Amlerova, J., Siala, K., Dedek, P., Watkins, S., Varvarovska, J., Stozicky, F., Pazdiora, P. and Schwarz, J. (2005) Effects of a specially designed fermented milk product containing probiotic Lactobacillus casei DN-114 001 and the eradication of H. pylori in children: a prospective randomized double-blind study. J. Clin. Gastroenterol. 39, 692-698. https://doi.org/10.1097/01.mcg.0000173855.77191.44
  178. Szajewska, H. and Mrukowicz, J. (2005) Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic- associated diarrhoea. Aliment Pharmacol. Ther. 22, 365-372. https://doi.org/10.1111/j.1365-2036.2005.02624.x
  179. Szajewska, H. and Mrukowicz, J. Z. (2001) Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. J. Pediatr. Gastroenterol. Nutr. 33(Suppl 2), S17-25. https://doi.org/10.1097/00005176-200110002-00004
  180. Szajewska, H., Ruszczynski, M. and Radzikowski, A. (2006) Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials. J. Pediatr. 149, 367-372. https://doi.org/10.1016/j.jpeds.2006.04.053
  181. Szymanski, H., Armanska, M., Kowalska-Duplaga, K. and Szajewska, H. (2008) Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02 in the prevention of antibiotic-associated diarrhea in children: a randomized controlled pilot trial. Digestion 78, 13-17. https://doi.org/10.1159/000151300
  182. Tallon, R., Arias, S., Bressollier, P. and Urdaci, M. C. (2007) Strain- and matrix-dependent adhesion of Lactobacillus plantarum is mediated by proteinaceous bacterial compounds. J. Appl. Microbiol. 102, 442-451.
  183. Tao, Y., Drabik, K. A., Waypa, T. S., Musch, M. W., Alverdy, J. C., Schneewind, O., Chang, E. B. and 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 Physiol. 290, C1018-1030.
  184. Tilg, H., Moschen, A. R. and Kaser, A. (2009) Obesity and the microbiota. Gastroenterology 136, 1476-1483. https://doi.org/10.1053/j.gastro.2009.03.030
  185. Toivanen, P. (2003) Normal intestinal microbiota in the aetiopathogenesis of rheumatoid arthritis. Ann. Rheum. Dis. 62, 807-811. https://doi.org/10.1136/ard.62.9.807
  186. Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., Egholm, M., Henrissat, B., Heath, A. C., Knight, R. and Gordon, J. I. (2009) A core gut microbiome in obese and lean twins. Nature 457, 480-484. https://doi.org/10.1038/nature07540
  187. Turnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R. and Gordon, J. I. (2007) The human microbiome project. Nature 449, 804-810. https://doi.org/10.1038/nature06244
  188. Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R. and Gordon, J. I. (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027-1031. https://doi.org/10.1038/nature05414
  189. Tursi, A., Brandimarte, G., Giorgetti, G. M., Forti, G., Modeo, M. E. and Gigliobianco, A. (2004) Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. Med. Sci. Monit. 10, PI126-131.
  190. Vaahtovuo, J., Munukka, E., Korkeamaki, M., Luukkainen, R. and Toivanen, P. (2008) Fecal microbiota in early rheumatoid arthritis. J Rheumatol. 35, 1500-1505.
  191. van Baarlen, P., Troost, F. J., van Hemert, S., van der Meer, C., de Vos, W. M., de Groot, P. J., Hooiveld, G. J., Brummer, R. J. and Kleerebezem, M. (2009) Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance. Proc. Natl. Acad. Sci. USA. 106, 2371-2376. https://doi.org/10.1073/pnas.0809919106
  192. Van Niel, C. W., Feudtner, C., Garrison, M. M. and Christakis, D. A. (2002) Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 109, 678-684. https://doi.org/10.1542/peds.109.4.678
  193. Veckman, V., Miettinen, M., Pirhonen, J., Siren, J., Matikainen, S. and Julkunen, I. (2004) Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells. J. Leukoc. Biol. 75, 764-771.
  194. Ventura, M., O'Flaherty, S., Claesson, M. J., Turroni, F., Klaenhammer, T. R., van Sinderen, D. and O'Toole, P. W. (2009) Genome-scale analyses of health-promoting bacteria: probiogenomics. Nat. Rev. Microbiol. 7, 61-71. https://doi.org/10.1038/nrmicro2047
  195. Venturi, A., Gionchetti, P., Rizzello, F., Johansson, R., Zucconi, E., Brigidi, P., Matteuzzi, D. and Campieri, M. (1999) Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol. Ther. 13, 1103-1108. https://doi.org/10.1046/j.1365-2036.1999.00560.x
  196. Vetter, M. L., Cardillo, S., Rickels, M. R. and Iqbal, N. (2009) Narrative review: effect of bariatric surgery on type 2 diabetes mellitus. Ann. Intern. Med. 150, 94-103. https://doi.org/10.7326/0003-4819-150-2-200901200-00007
  197. Villar-Garea, A. and Esteller, M. (2004) Histone deacetylase inhibitors: understanding a new wave of anticancer agents. Int. J. Cancer 112, 171-178. https://doi.org/10.1002/ijc.20372
  198. Waldecker, M., Kautenburger, T., Daumann, H., Busch, C. and Schrenk, D. (2008) Inhibition of histone-deacetylase activity by shortchain fatty acids and some polyphenol metabolites formed in the colon. J. Nutr. Biochem. 19, 587-593. https://doi.org/10.1016/j.jnutbio.2007.08.002
  199. Wall, R., Ross, R. P., Shanahan, F., O'Mahony, L., O'Mahony, C., Coakley, M., Hart, O., Lawlor, P., Quigley, E. M., Kiely, B., Fitzgerald, G. F. and Stanton, C. (2009) Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues. Am. J. Clin. Nutr. 89, 1393-1401. https://doi.org/10.3945/ajcn.2008.27023
  200. Wang, Z., Xiao, G., Yao, Y., Guo, S., Lu, K. and Sheng, Z. (2006) The role of bifidobacteria in gut barrier function after thermal injury in rats. J. Trauma 61, 650-657. https://doi.org/10.1097/01.ta.0000196574.70614.27
  201. Wehkamp, J., Harder, J., Wehkamp, K., Wehkamp-von Meissner, B., Schlee, M., Enders, C., Sonnenborn, U., Nuding, S., Bengmark, S., Fellermann, K., Schroder, J. M. and Stange, E. F. (2004) NFkappaB-and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium. Infect. Immun. 72, 5750-5758. https://doi.org/10.1128/IAI.72.10.5750-5758.2004
  202. Wellen, K. E. and Hotamisligil, G. S. (2005) Inflammation, stress, and diabetes. J. Clin. Invest. 115, 1111-1119. https://doi.org/10.1172/JCI200525102
  203. Wen, L., Ley, R. E., Volchkov, P. Y., Stranges, P. B., Avanesyan, L., Stonebraker, A. C., Hu, C., Wong, F. S., Szot, G. L., Bluestone, J. A., Gordon, J. I. and Chervonsky, A. V. (2008) Innate immunity and intestinal microbiota in the development of Type 1 diabetes. Nature 455, 1109-1113. https://doi.org/10.1038/nature07336
  204. Wenus, C., Goll, R., Loken, E. B., Biong, A. S., Halvorsen, D. S. and Florholmen, J. (2008) Prevention of antibiotic-associated diarrhoea by a fermented probiotic milk drink. Eur. J. Clin. Nutr. 62, 299-301. https://doi.org/10.1038/sj.ejcn.1602718
  205. Wilson, A. J., Byun, D. S., Popova, N., Murray, L. B., L'Italien, K., Sowa, Y., Arango, D., Velcich, A., Augenlicht, L. H. and Mariadason, J. M. (2006) Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J. Biol. Chem. 281, 13548-13558. https://doi.org/10.1074/jbc.M510023200
  206. Wolowczuk, I., Verwaerde, C., Viltart, O., Delanoye, A., Delacre, M., Pot, B. and Grangette, C. (2008) Feeding our immune system: impact on metabolism. Clin. Dev. Immunol. 2008, 639803.
  207. Wright, S. D., Ramos, R. A., Tobias, P. S., Ulevitch, R. J. and Mathison, J. C. (1990) CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249, 1431-1433. https://doi.org/10.1126/science.1698311
  208. Xavier, R. J. and Podolsky, D. K. (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427-434. https://doi.org/10.1038/nature06005
  209. Xiong, Y., Miyamoto, N., Shibata, K., Valasek, M. A., Motoike, T., Kedzierski, R. M. and Yanagisawa, M. (2004) Short-chain fatty acids stimulate leptin production in adipocytes through the G proteincoupled receptor GPR41. Proc. Natl. Acad. Sci. USA 101, 1045-1050. https://doi.org/10.1073/pnas.2637002100
  210. Yan, F., Cao, H., Cover, T. L., Whitehead, R., Washington, M. K. and Polk, D. B. (2007) Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. Gastroenterology 132, 562-575. https://doi.org/10.1053/j.gastro.2006.11.022
  211. Yan, F. and Polk, D. B. (2002) Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J. Biol. Chem. 277, 50959-50965. https://doi.org/10.1074/jbc.M207050200
  212. Yan, F. and Polk, D. B. (2004) Commensal bacteria in the gut: learning who our friends are. Curr. Opin. Gastroenterol. 20, 565-571. https://doi.org/10.1097/00001574-200411000-00011
  213. Yan, F. and Polk, D. B. (2006) Probiotics as functional food in the treatment of diarrhea. Curr. Opin. Clin. Nutr. Metab. Care 9, 717-721. https://doi.org/10.1097/01.mco.0000247477.02650.51
  214. Zocco, M. A., dal Verme, L. Z., Cremonini, F., Piscaglia, A. C., Nista, E. C., Candelli, M., Novi, M., Rigante, D., Cazzato, I. A., Ojetti, V., Armuzzi, A., Gasbarrini, G. and Gasbarrini, A. (2006) Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol. Ther. 23, 1567-1574. https://doi.org/10.1111/j.1365-2036.2006.02927.x
  215. Zoetendal, E. G., Rajilic-Stojanovic, M. and de Vos, W. M. (2008) High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 57, 1605-1615. https://doi.org/10.1136/gut.2007.133603
  216. Zoetendal, E. G., Vaughan, E. E. and de Vos, W. M. (2006) A microbial world within us. Mol. Microbiol. 59, 1639-1650. https://doi.org/10.1111/j.1365-2958.2006.05056.x
  217. Zyrek, A. A., Cichon, C., Helms, S., Enders, C., Sonnenborn, U. and Schmidt, M. A. (2007) Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol. 9, 804-816. https://doi.org/10.1111/j.1462-5822.2006.00836.x

Cited by

  1. Influence of fermented milk products, prebiotics and probiotics on microbiota composition and health vol.27, pp.1, 2013, https://doi.org/10.1016/j.bpg.2013.04.004
  2. Probiotics for weight loss: a systematic review and meta-analysis vol.35, pp.7, 2015, https://doi.org/10.1016/j.nutres.2015.05.008
  3. Prebiotic effects of alfalfa (Medicago sativa) fiber on cecal bacterial composition, short-chain fatty acids, and diarrhea incidence in weaning piglets vol.9, pp.24, 2011, https://doi.org/10.1039/c9ra01251f