The impact of gut microbiota in human health and diseases: Implication for therapeutic potential

Biomolecules and Therapeutics

Volumn 19, Issue 2, 2011, Pages 155-173

  Ha, Eun Mi ^a  

^a Catholic University of Daegu   (South Korea)

Author keywords

Gut microbiota; Homeostasis; Host microbes interaction; Probiotics; Therapy

Indexed keywords

BUTYRIC ACID; GAMMA INTERFERON; GRANULOCYTE COLONY STIMULATING FACTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; INTERLEUKIN 12; PROBIOTIC AGENT; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; VSL3;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; AUTOIMMUNITY; BACTERIAL IMMUNITY; BACTEROIDES FRAGILIS; BACTEROIDES THETAIOTAOMICRON; BIFIDOBACTERIUM ANIMALIS; BIFIDOBACTERIUM LONGUM INFANTIS; CELL SURVIVAL; CLOSTRIDIUM; COLITIS; COMMENSALISM; COMPETITIVE INHIBITION; CROHN DISEASE; CYTOKINE PRODUCTION; DIARRHEA; DRUG EFFECT; DRUG MECHANISM; ENERGY BALANCE; ENTERITIS; ESCHERICHIA COLI; FIRMICUTES; HOST PATHOGEN INTERACTION; HUMAN; ILEITIS; IMMUNOCOMPETENT CELL; IMMUNOREGULATION; INFLAMMATION; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE EPITHELIUM CELL; INTESTINE FLORA; INTESTINE MUCOSA PERMEABILITY; LACTOBACILLUS; LACTOBACILLUS ACIDOPHILUS; LACTOBACILLUS CASEI; LACTOBACILLUS GASSERI; LACTOBACILLUS JOHNSONII; LACTOBACILLUS REUTERI; LACTOBACILLUS RHAMNOSUS; LACTOCOCCUS LACTIS; METABOLIC SYNDROME X; MUCOSAL IMMUNITY; OBESITY; PORPHYROMONAS; PREVOTELLA; PROTECTION; RESPIRATORY TRACT ALLERGY; RHEUMATOID ARTHRITIS; TIGHT JUNCTION; ULCERATIVE COLITIS;

BACTERIA (MICROORGANISMS);

EID: 79956095833     PISSN: 19769148     EISSN: 20054483     Source Type: Journal    
DOI: 10.4062/biomolther.2011.19.2.155     Document Type: Article

References (217)

1. Abreu, M. T., Fukata M. and Arditi M. (2005) TLR signaling in the gut in health and disease. J. Immunol. 174, 4453-4460.
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.
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.
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.
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.
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.
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.
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.
11. Baggio, L. L. and Drucker, D. J. (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology. 132, 2131-2157.
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.
13. Bauer, H., Horowitz, R. E., Levenson, S. M. and Popper, H. (1963) The response of the lymphatic tissue to the microbial flora. 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.
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.
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.
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.
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.
21. Caballero, B. (2007) The global epidemic of obesity: an overview. Epidemiol. Rev. 29, 1-5.
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.
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.
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.
25. Cani, P. D. and Delzenne, N. M. (2007) Gut microflora as a target for energy and metabolic homeostasis. Curr. Opin. Clin. Nutr. Metab. Care 10, 729-734.
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.
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.
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 microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 50, 2374-2383.
29. Cario, E. and Podolsky, D. K. (2006) Toll-like receptor signaling and its relevance to intestinal inflammation. Ann. N Y Acad. Sci. 1072, 332-338.
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.
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.
32. Chichlowski, M. and Hale, L. P. (2008) Bacterial-mucosal interactions in inflammatory bowel disease: an alliance gone bad. Am. J. Physiol. Gastrointest Liver Physiol. 295, G1139-1149.
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.
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.
35. Collado, M. C., Hernandez, M. and Sanz, Y. (2005) Production of bacteriocin-like inhibitory compounds by human fecal Bifidobacterium 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.
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 inflammatory bowel disease. Gut 55, 1760-1767.
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.
40. Cotter, P. D., Hill, C. and Ross, R. P. (2005) Bacteriocins: developing innate immunity for food. Nat. Rev. Microbiol. 3, 777-788.
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.
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.
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.
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.
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.
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.
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.
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.
51. Drakes, M., Blanchard, T. and Czinn, S. (2004) Bacterial probiotic modulation of dendritic cells. Infect. Immun. 72, 3299-3309.
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.
53. Edwards, C. J. and Cooper, C. (2006) Early environmental factors and rheumatoid arthritis. Clin. Exp. Immunol. 143, 1-5.
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.
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.
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.
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.
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 inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial. Gut 54, 242-249.
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.
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.
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.
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.
64. Goossens, G. H. (2008) The role of adipose tissue dysfunction in the pathogenesis of obesity-related insulin resistance. Physiol. Behav. 94, 206-218.
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.
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.
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.
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.
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.
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 modifications. Nat. Immunol. 3, 354-359.
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.
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.
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.
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: randomized double blind placebo controlled trial. BMJ 335, 80.
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.
77. Hooper, L. V. and Gordon, J. I. (2001) Commensal host-bacterial relationships in the gut. Science 292, 1115-1118.
78. Hooper, L. V. and Macpherson, A. J. (2010) Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat. Rev. Immunol. 10, 159-169.
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.
80. Hotamisligil, G. S. (2006) Inflammation and metabolic disorders. Nature 444, 860-867.
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.
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.
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.
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, 123-129.
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.
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.
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.
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.
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 bifidobacteria-fermented milk on active ulcerative colitis. Aliment Pharmacol. Ther. 20, 1133-1141.
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.
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.
94. Knight, P., Campbell, B. J. and Rhodes, J. M. (2008) Host-bacteria interaction in inflammatory bowel disease. Br. Med. Bull. 88, 95-113.
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 bifidogenic dose of inulin in healthy humans. Eur. J. Clin. Nutr. 61, 1189-1195.
97. Kraehenbuhl, J. P. and Corbett, M. (2004) Immunology. Keeping the gut microflora at bay. Science 303, 1624-1625.
98. Krieg, A. M. (2003) CpG motifs: the active ingredient in bacterial extracts? Nat. Med. 9, 831-835.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
110. Lichtenberger, G. S., Flavell, R. A. and Alexopoulou, L. (2004) Innate immunity and apoptosis in IBD. Inflamm. Bowel Dis. 10(Suppl 1), S58-S62.
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.
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 169-170.
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.
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.
115. Macfarlane, S., Macfarlane, G. T. and Cummings, J. H. (2006) Review article: prebiotics in the gastrointestinal tract. Aliment Pharmacol. Ther. 24, 701-714.
116. Macpherson, A. J. and Uhr, T. (2004) Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303, 1662-1625.
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.
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.
119. Mariadason, J. M. (2008) HDACs and HDAC inhibitors in colon cancer. Epigenetics 3, 28-37.
120. Marks, P. A. and Xu, W. S. (2009) Histone deacetylase inhibitors: Potential in cancer therapy. J. Cell Biochem. 107, 600-608.
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., Coffin, 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
133. Mylonaki, M., Rayment, N. B., Rampton, D. S., Hudspith, B. N. and Brostoff, J. (2005) Molecular characterization of rectal mucosaassociated bacterial flora in inflammatory bowel disease. Inflamm. Bowel Dis. 11, 481-487.
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.
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.
136. Neish, A. S. (2009) Microbes in gastrointestinal health and disease. Gastroenterology. 136, 65-80.
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.
138. Noverr, M. C. and Huffnagle, G. B. (2004) Does the microbiota regulate immune responses outside the gut? Trends Microbiol. 12, 562-568.
139. Noverr, M. C. and Huffnagle, G. B. (2005) The 'microflora hypothesis' of allergic diseases. Clin. Exp. Allergy 35, 1511-1520.
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 microflora in patients with active inflammatory bowel disease. Gut 53, 685-693.
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-G626.
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.
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.
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.
146. Parnell, J. A. and Reimer, R. A. (2009) Weight loss during oligofruc tose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am. J. Clin. Nutr. 89, 1751-1759.
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.
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.
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.
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.
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.
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 antiinflammatory effects of probiotics in murine experimental colitis. Gastroenterology. 126, 520-528.
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.
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.
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.
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.
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.
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.
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.
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.
161. Sanders, M. E. (2003) Probiotics: considerations for human health. Nutr. Rev. 61, 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.
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.
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.
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.
166. Servin, A. L. (2004) Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol. Rev. 28, 405-440.
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-G1069.
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.
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 efficacy 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.
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.
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.
174. Strober, W., Fuss, I. and Mannon, P. (2007) The fundamental basis of inflammatory bowel disease. J. Clin. Invest. 117, 514-521.
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.
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.
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.
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.
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-S25.
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.
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.
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-C1030.
184. Tilg, H., Moschen, A. R. and Kaser, A. (2009) Obesity and the microbiota. Gastroenterology 136, 1476-1483.
185. Toivanen, P. (2003) Normal intestinal microbiota in the aetiopathogenesis of rheumatoid arthritis. Ann. Rheum. Dis. 62, 807-811.
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.
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.
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.
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-PI131.
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.
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.
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.
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.
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.
197. Villar-Garea, A. and Esteller, M. (2004) Histone deacetylase inhibitors: understanding a new wave of anticancer agents. Int. J. Cancer 112, 171-178.
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.
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.
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.
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.
202. Wellen, K. E. and Hotamisligil, G. S. (2005) Inflammation, stress, and diabetes. J. Clin. Invest. 115, 1111-1119.
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.
204. Wenus, C., Goll, R., Loken, E. B., Biong, A. S., Halvorsen, D. S. and Florholmen, J. (2008) Prevention of antibiotic-associated diarrhea by a fermented probiotic milk drink. Eur. J. Clin. Nutr. 62, 299-301.
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.
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.
208. Xavier, R. J. and Podolsky, D. K. (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427-434.
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.
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.
211. Yan, F. and Polk, D. B. (2002) Probiotic bacterium prevents cytokineinduced apoptosis in intestinal epithelial cells. J. Biol. Chem. 277, 50959-50965.
212. Yan, F. and Polk, D. B. (2004) Commensal bacteria in the gut: learning who our friends are. Curr. Opin. Gastroenterol. 20, 565-571.
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.
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.
215. Zoetendal, E. G., Rajilic-Stojanovic, M. and de Vos, W. M. (2008) Highthroughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut 57, 1605-1615.
216. Zoetendal, E. G., Vaughan, E. E. and de Vos, W. M. (2006) A microbial world within us. Mol. Microbiol. 59, 1639-1650.
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.