Skip to main content

Advertisement

Log in

The intestinal microbiota: its role in health and disease

  • Review
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The intestinal microbiota (previously referred to as “intestinal flora”) has entered the focus of research interest not only in microbiology but also in medicine. Huge progress has been made with respect to the analysis of composition and functions of the human microbiota. An “imbalance” of the microbiota, frequently also called a “dysbiosis,” has been associated with different diseases in recent years. Crohn’s disease and ulcerative colitis as two major forms of inflammatory bowel disease, irritable bowel syndrome (IBS) and some infectious intestinal diseases such as Clostridium difficile colitis feature a dysbiosis of the intestinal flora. Whereas this is somehow expected or less surprising, an imbalance of the microbiota or an enrichment of specific bacterial strains in the flora has been associated with an increasing number of other diseases such as diabetes, metabolic syndrome, non-alcoholic fatty liver disease or steatohepatitis and even psychiatric disorders such as depression or multiple sclerosis. It is important to understand the different aspects of potential contributions of the microbiota to pathophysiology of the mentioned diseases.

Conclusion: With the present manuscript, we aim to summarize the current knowledge and provide an overview of the different concepts on how bacteria contribute to health and disease in animal models and—more importantly—humans. In addition, it has to be borne in mind that we are only at the very beginning to understand the complex mechanisms of host-microbial interactions.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Alam C, Bittoun E, Bhagwat D, Valkonen S, Saari A, Jaakkola U, Eerola E, Huovinen P, Hanninen A (2011) Effects of a germ-free environment on gut immune regulation and diabetes progression in non-obese diabetic (NOD) mice. Diabetologia 54(6):1398–1406. doi:10.1007/s00125-011-2097-5

    CAS  PubMed  Google Scholar 

  2. Albenberg LG, Wu GD (2014) Diet and the intestinal microbiome: associations, functions, and implications for health and disease. Gastroenterology 146(6):1564–1572. doi:10.1053/j.gastro.2014.01.058

    CAS  PubMed  Google Scholar 

  3. Alkanani AK, Hara N, Lien E, Ir D, Kotter CV, Robertson CE, Wagner BD, Frank DN, Zipris D (2014) Induction of diabetes in the RIP-B7.1 mouse model is critically dependent on TLR3 and MyD88 pathways and is associated with alterations in the intestinal microbiome. Diabetes 63(2):619–631. doi:10.2337/db13-1007

    CAS  PubMed  Google Scholar 

  4. Andersson M, Bjornham O, Svantesson M, Badahdah A, Uhlin BE, Bullitt E (2012) A structural basis for sustained bacterial adhesion: biomechanical properties of CFA/I pili. J Mol Biol 415(5):918–928. doi:10.1016/j.jmb.2011.12.006

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Angelberger S, Reinisch W, Makristathis A, Lichtenberger C, Dejaco C, Papay P, Novacek G, Trauner M, Loy A, Berry D (2013) Temporal bacterial community dynamics vary among ulcerative colitis patients after fecal microbiota transplantation. Am J Gastroenterol 108(10):1620–1630. doi:10.1038/ajg.2013.257

    CAS  PubMed  Google Scholar 

  6. Antoni L, Nuding S, Wehkamp J, Stange EF (2014) Intestinal barrier in inflammatory bowel disease. World J Gastroenterol : WJG 20(5):1165–1179. doi:10.3748/wjg.v20.i5.1165

    PubMed Central  PubMed  Google Scholar 

  7. Antoni L, Nuding S, Weller D, Gersemann M, Ott G, Wehkamp J, Stange EF (2013) Human colonic mucus is a reservoir for antimicrobial peptides. J Crohn’s Colitis 7(12):e652–64. doi:10.1016/j.crohns.2013.05.006

    Google Scholar 

  8. Arthur JC, Perez-Chanona E, Muhlbauer M, Tomkovich S, Uronis JM, Fan TJ, Campbell BJ, Abujamel T, Dogan B, Rogers AB, Rhodes JM, Stintzi A, Simpson KW, Hansen JJ, Keku TO, Fodor AA, Jobin C (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338(6103):120–123. doi:10.1126/science.1224820

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Bach J (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347(12):911–920. doi:10.1056/NEJMra020100

    PubMed  Google Scholar 

  10. Backhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101(44):15718–15723. doi:10.1073/pnas.0407076101

    PubMed Central  PubMed  Google Scholar 

  11. Backhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307(5717):1915–1920. doi:10.1126/science.1104816

    PubMed  Google Scholar 

  12. Barnich N, Darfeuille-Michaud A (2010) Abnormal CEACAM6 expression in Crohn disease patients favors gut colonization and inflammation by adherent-invasive E. coli. Virulence 1(4):281–282. doi:10.4161/viru.1.4.11510

    PubMed  Google Scholar 

  13. Barreau F, Madre C, Meinzer U, Berrebi D, Dussaillant M, Merlin F, Eckmann L, Karin M, Sterkers G, Bonacorsi S, Lesuffleur T, Hugot JP (2010) Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer’s patches. Gut 59(2):207–217. doi:10.1136/gut.2008.171546

    CAS  PubMed  Google Scholar 

  14. Barreau F, Meinzer U, Chareyre F, Berrebi D, Niwa-Kawakita M, Dussaillant M, Foligne B, Ollendorff V, Heyman M, Bonacorsi S, Lesuffleur T, Sterkers G, Giovannini M, Hugot JP (2007) CARD15/NOD2 is required for Peyer’s patches homeostasis in mice. PLoS One 2(6):e523. doi:10.1371/journal.pone.0000523

    PubMed Central  PubMed  Google Scholar 

  15. Barthel M, Hapfelmeier S, Quintanilla-Martinez L, Kremer M, Rohde M, Hogardt M, Pfeffer K, Russmann H, Hardt WD (2003) Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun 71(5):2839–2858

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Bartlett AH, Park PW (2010) Proteoglycans in host-pathogen interactions: molecular mechanisms and therapeutic implications. Exp Rev Mol Med 12:e5. doi:10.1017/S1462399409001367

    Google Scholar 

  17. Beaugerie L, Massot N, Carbonnel F, Cattan S, Gendre JP, Cosnes J (2001) Impact of cessation of smoking on the course of ulcerative colitis. Am J Gastroenterol 96(7):2113–2116. doi:10.1111/j.1572-0241.2001.03944.x

    CAS  PubMed  Google Scholar 

  18. Belley A, Keller K, Gottke M, Chadee K (1999) Intestinal mucins in colonization and host defense against pathogens. AmJTrop Med Hyg 60(4 Suppl):10–15

    CAS  Google Scholar 

  19. Benjamin JL, Hedin CR, Koutsoumpas A, Ng SC, McCarthy NE, Prescott NJ, Pessoa-Lopes P, Mathew CG, Sanderson J, Hart AL, Kamm MA, Knight SC, Forbes A, Stagg AJ, Lindsay JO, Whelan K (2012) Smokers with active Crohn’s disease have a clinically relevant dysbiosis of the gastrointestinal microbiota. Inflamm Bowel Dis 18(6):1092–1100. doi:10.1002/ibd.21864

    PubMed  Google Scholar 

  20. Biasucci G, Benenati B, Morelli L, Bessi E, Boehm G (2008) Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr 138(9):1796S–1800S

    CAS  PubMed  Google Scholar 

  21. Biedermann L, Zeitz J, Mwinyi J, Sutter-Minder E, Rehman A, Ott SJ, Steurer-Stey C, Frei A, Frei P, Scharl M, Loessner MJ, Vavricka SR, Fried M, Schreiber S, Schuppler M, Rogler G (2013) Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PLoS One 8(3):e59260. doi:10.1371/journal.pone.0059260

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Boerner BP, Sarvetnick NE (2011) Type 1 diabetes: role of intestinal microbiome in humans and mice. Ann N Y Acad Sci 1243:103–118. doi:10.1111/j.1749-6632.2011.06340.x

    CAS  PubMed  Google Scholar 

  23. Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, Casella G, Drew JC, Ilonen J, Knip M, Hyoty H, Veijola R, Simell T, Simell O, Neu J, Wasserfall CH, Schatz D, Atkinson MA, Triplett EW (2011) Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS One 6(10):e25792. doi:10.1371/journal.pone.0025792

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Brusca SB, Abramson SB, Scher JU (2014) Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol 26(1):101–107. doi:10.1097/BOR.0000000000000008

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Bultman SJ (2014) Emerging roles of the microbiome in cancer. Carcinogenesis 35(2):249–255. doi:10.1093/carcin/bgt392

    CAS  PubMed  Google Scholar 

  26. Candela M, Biagi E, Maccaferri S, Turroni S, Brigidi P (2012) Intestinal microbiota is a plastic factor responding to environmental changes. Trends Microbiol 20(8):385–391. doi:10.1016/j.tim.2012.05.003

    CAS  PubMed  Google Scholar 

  27. Candela M, Rampelli S, Turroni S, Severgnini M, Consolandi C, de Bellis G, Masetti R, Ricci G, Pession A, Brigidi P (2012) Unbalance of intestinal microbiota in atopic children. BMC Microbiol 12:95. doi:10.1186/1471-2180-12-95

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Cani PD, Possemiers S, van de Wiele T, Guiot Y, Everard A, Rottier O, Geurts L, Naslain D, Neyrinck A, Lambert DM, Muccioli GG, Delzenne NM (2009) Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut 58(8):1091–1103. doi:10.1136/gut.2008.165886

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Carroll IM, Chang YH, Park J, Sartor RB, Ringel Y (2010) Luminal and mucosal-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Gut Pathog 2(1):19. doi:10.1186/1757-4749-2-19

    PubMed Central  PubMed  Google Scholar 

  30. Carvalho FA, Barnich N, Sivignon A, Darcha C, Chan CH, Stanners CP, Darfeuille-Michaud A (2009) Crohn’s disease adherent-invasive Escherichia coli colonize and induce strong gut inflammation in transgenic mice expressing human CEACAM. J Exp Med 206(10):2179–2189. doi:10.1084/jem.20090741

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Chassaing B, Gewirtz AT (2014) Gut microbiota, low-grade inflammation, and metabolic syndrome. Toxicol Pathol 42(1):49–53. doi:10.1177/0192623313508481

    PubMed  Google Scholar 

  32. Chu H, Pazgier M, Jung G, Nuccio SP, Castillo PA, de Jong MF, Winter MG, Winter SE, Wehkamp J, Shen B, Salzman NH, Underwood MA, Tsolis RM, Young GM, Lu W, Lehrer RI, Baumler AJ, Bevins CL (2012) Human alpha-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science 337(6093):477–481. doi:10.1126/science.1218831

    CAS  PubMed  Google Scholar 

  33. Claesson MJ, Cusack S, O’Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, van Sinderen D, O’Connor M, Harnedy N, O’Connor K, Henry C, O’Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O’Toole PW (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U S A 108(Suppl 1):4586–4591. doi:10.1073/pnas.1000097107

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Clarke SF, Murphy EF, O’Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O’Reilly M, Jeffery IB, Wood-Martin R, Kerins DM, Quigley E, Ross RP, O’Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD (2014) Exercise and associated dietary extremes impact on gut microbial diversity. Gut. doi:10.1136/gutjnl-2013-306541

    Google Scholar 

  35. Codling C, O’Mahony L, Shanahan F, Quigley EM, Marchesi JR (2010) A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. Dig Dis Sci 55(2):392–397. doi:10.1007/s10620-009-0934-x

    PubMed  Google Scholar 

  36. Cordell B, McCarthy J (2013) A case study of gut fermentation syndrome (auto-brewery) with Saccharomyces cerevisiae as the causative organism. Int J Clin Med 4(7):309–312

    Google Scholar 

  37. Cosnes J (2010) Smoking, physical activity, nutrition and lifestyle: environmental factors and their impact on IBD. Dig Dis 28(3):411–417. doi:10.1159/000320395

    PubMed  Google Scholar 

  38. Cosnes J, Beaugerie L, Carbonnel F, Gendre JP (2001) Smoking cessation and the course of Crohn’s disease: an intervention study. Gastroenterology 120(5):1093–1099. doi:10.1053/gast.2001.23231

    CAS  PubMed  Google Scholar 

  39. Costello EK, Stagaman K, Dethlefsen L, Bohannan BJ, Relman DA (2012) The application of ecological theory toward an understanding of the human microbiome. Science 336(6086):1255–1262. doi:10.1126/science.1224203

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Couturier-Maillard A, Secher T, Rehman A, Normand S, de Arcangelis A, Haesler R, Huot L, Grandjean T, Bressenot A, Delanoye-Crespin A, Gaillot O, Schreiber S, Lemoine Y, Ryffel B, Hot D, Nunez G, Chen G, Rosenstiel P, Chamaillard M (2013) NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest 123(2):700–711. doi:10.1172/JCI62236

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Damman CJ, Miller SI, Surawicz CM, Zisman TL (2012) The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation? Am J Gastroenterol 107(10):1452–1459. doi:10.1038/ajg.2012.93

    PubMed  Google Scholar 

  42. Darfeuille-Michaud A, Boudeau J, Bulois P, Neut C, Glasser AL, Barnich N, Bringer MA, Swidsinski A, Beaugerie L, Colombel JF (2004) High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology 127(2):412–421

    PubMed  Google Scholar 

  43. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ (2014) Diet rapidly and reproducibly alters the human gut microbiome. Nature 505(7484):559–563. doi:10.1038/nature12820

    CAS  PubMed Central  PubMed  Google Scholar 

  44. de Angelis M, Piccolo M, Vannini L, Siragusa S, de Giacomo A, Serrazzanetti DI, Cristofori F, Guerzoni ME, Gobbetti M, Francavilla R (2013) Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PLoS One 8(10):e76993. doi:10.1371/journal.pone.0076993

    PubMed Central  PubMed  Google Scholar 

  45. de Theije CG, Wopereis H, Ramadan M, van Eijndthoven T, Lambert J, Knol J, Garssen J, Kraneveld AD, Oozeer R (2014) Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav Immun 37:197–206. doi:10.1016/j.bbi.2013.12.005

    PubMed  Google Scholar 

  46. Dekio I, Hayashi H, Sakamoto M, Kitahara M, Nishikawa T, Suematsu M, Benno Y (2005) Detection of potentially novel bacterial components of the human skin microbiota using culture-independent molecular profiling. J Med Microbiol 54(Pt 12):1231–1238. doi:10.1099/jmm. 0.46075-0

    CAS  PubMed  Google Scholar 

  47. Dessein R, Peyrin-Biroulet L, Chamaillard M (2009) Intestinal microbiota gives a nod to the hygiene hypothesis in type 1 diabetes. Gastroenterology 137(1):381–383. doi:10.1053/j.gastro.2009.05.026

    PubMed  Google Scholar 

  48. Dethlefsen L, Huse S, Sogin ML, Relman DA (2008) The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol 6(11):e280. doi:10.1371/journal.pbio.0060280

    PubMed Central  PubMed  Google Scholar 

  49. Dethlefsen L, Relman DA (2011) Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci 108(Supplement 1):4554–4561. doi:10.1073/pnas.1000087107

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Devaraj S, Hemarajata P, Versalovic J (2013) The human gut microbiome and body metabolism: implications for obesity and diabetes. Clin Chem 59(4):617–628. doi:10.1373/clinchem.2012.187617

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Dinan TG, Cryan JF (2013) Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil : Off J Eur Gastrointest Motil Soc 25(9):713–719. doi:10.1111/nmo.12198

    CAS  Google Scholar 

  52. Docktor MJ, Paster BJ, Abramowicz S, Ingram J, Wang YE, Correll M, Jiang H, Cotton SL, Kokaras AS, Bousvaros A (2012) Alterations in diversity of the oral microbiome in pediatric inflammatory bowel disease. Inflamm Bowel Dis 18(5):935–942. doi:10.1002/ibd.21874

    PubMed Central  PubMed  Google Scholar 

  53. Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R (2011) Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology 140(6):1713–1719

    CAS  PubMed  Google Scholar 

  54. Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci 107(26):11971–11975

    PubMed Central  PubMed  Google Scholar 

  55. Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, Thomas G, Barbu V, Humbert L, Despras G, Bridonneau C, Dumetz F, Grill JP, Masliah J, Beaugerie L, Cosnes J, Chazouilleres O, Poupon R, Wolf C, Mallet JM, Langella P, Trugnan G, Sokol H, Seksik P (2013) Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 62(4):531–539. doi:10.1136/gutjnl-2012-302578

    CAS  PubMed  Google Scholar 

  56. Dunne JL, Triplett EW, Gevers D, Xavier R, Insel R, Danska J, Atkinson MA (2014) The intestinal microbiome in type 1 diabetes. Clin Exp Immunol 177(1):30–37. doi:10.1111/cei.12321

    CAS  PubMed  Google Scholar 

  57. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308(5728):1635–1638. doi:10.1126/science.1110591

    PubMed Central  PubMed  Google Scholar 

  58. Ellinghaus D, Baurecht H, Esparza-Gordillo J, Rodriguez E, Matanovic A, Marenholz I, Hubner N, Schaarschmidt H, Novak N, Michel S, Maintz L, Werfel T, Meyer-Hoffert U, Hotze M, Prokisch H, Heim K, Herder C, Hirota T, Tamari M, Kubo M, Takahashi A, Nakamura Y, Tsoi LC, Stuart P, Elder JT, Sun L, Zuo X, Yang S, Zhang X, Hoffmann P, Nothen MM, Folster-Holst R, Winkelmann J, Illig T, Boehm BO, Duerr RH, Buning C, Brand S, Glas J, McAleer MA, Fahy CM, Kabesch M, Brown S, McLean WH, Irvine AD, Schreiber S, Lee YA, Franke A, Weidinger S (2013) High-density genotyping study identifies four new susceptibility loci for atopic dermatitis. Nat Genet 45(7):808–812. doi:10.1038/ng.2642

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Faith JJ, McNulty NP, Rey FE, Gordon JI (2011) Predicting a human gut microbiota’s response to diet in gnotobiotic mice. Science 333(6038):101–104. doi:10.1126/science.1206025

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Fasano A, Shea-Donohue T (2005) Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. Nat Clin Prac Gastroenterol Hepatol 2(9):416–422. doi:10.1038/ncpgasthep0259

    CAS  Google Scholar 

  61. Fellermann K, Wehkamp J, Herrlinger KR, Stange EF (2003) Crohn’s disease: a defensin deficiency syndrome? Eur J Gastroenterol Hepatol 15(6):627–634. doi:10.1097/01.meg.0000059151.68845.88

    CAS  PubMed  Google Scholar 

  62. Foster JA, Krone SM, Forney LJ (2008) Application of ecological network theory to the human microbiome. Interdiscip Perspect Infect Dis 2008:839501. doi:10.1155/2008/839501

    PubMed Central  PubMed  Google Scholar 

  63. Gaboriau-Routhiau V, Lecuyer E, Cerf-Bensussan N (2011) Role of microbiota in postnatal maturation of intestinal T-cell responses. Curr Opin Gastroenterol 27(6):502–508. doi:10.1097/MOG.0b013e32834bb82b

    CAS  PubMed  Google Scholar 

  64. Gent AE, Hellier MD, Grace RH, Swarbrick ET, Coggon D (1994) Inflammatory bowel disease and domestic hygiene in infancy. Lancet 343(8900):766–767

    CAS  PubMed  Google Scholar 

  65. Ghoshal S, Witta J, Zhong J, de Villiers W, Eckhardt E (2009) Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res 50(1):90–97. doi:10.1194/jlr. M800156-JLR200

    CAS  PubMed  Google Scholar 

  66. Groisman EA, Casadesus J (2005) The origin and evolution of human pathogens. Mol Microbiol 56(1):1–7. doi:10.1111/j.1365-2958.2005.04564.x

    CAS  PubMed  Google Scholar 

  67. Grönlund MM, Lehtonen OP, Eerola E, Kero P (1999) Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr 28(1):19–25

    PubMed  Google Scholar 

  68. Guarino A, Wudy A, Basile F, Ruberto E, Buccigrossi V (2012) Composition and roles of intestinal microbiota in children. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 25 Suppl 1:63–66. doi:10.3109/14767058.2012.663231

  69. Guirado M, Gil H, Saenz-Lopez P, Reinboth J, Garrido F, Cozar JM, Ruiz-Cabello F, Carretero R (2012) Association between C13ORF31, NOD2, RIPK2 and TLR10 polymorphisms and urothelial bladder cancer. Hum Immunol 73(6):668–672. doi:10.1016/j.humimm.2012.03.006

    CAS  PubMed  Google Scholar 

  70. Gutierrez A, Scharl M, Sempere L, Holler E, Zapater P, Almenta I, Gonzalez-Navajas JM, Such J, Wiest R, Rogler G, Frances R (2014) Genetic susceptibility to increased bacterial translocation influences the response to biological therapy in patients with Crohn’s disease. Gut 63(2):272–280. doi:10.1136/gutjnl-2012-303557

    CAS  PubMed  Google Scholar 

  71. Hapfelmeier S, Hardt WD (2005) A mouse model for S. typhimurium-induced enterocolitis. Trends Microbiol 13(10):497–503. doi:10.1016/j.tim.2005.08.008

    CAS  PubMed  Google Scholar 

  72. Hara N, Alkanani AK, Ir D, Robertson CE, Wagner BD, Frank DN, Zipris D (2013) The role of the intestinal microbiota in type 1 diabetes. Clin Immunol 146(2):112–119. doi:10.1016/j.clim.2012.12.001

    CAS  PubMed  Google Scholar 

  73. Hedin CR, McCarthy NE, Louis P, Farquharson FM, McCartney S, Taylor K, Prescott NJ, Murrells T, Stagg AJ, Whelan K, Lindsay JO (2014) Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn’s disease and their unaffected siblings. Gut. doi:10.1136/gutjnl-2013-306226

    PubMed  Google Scholar 

  74. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, Thaiss CA, Kau AL, Eisenbarth SC, Jurczak MJ, Camporez JP, Shulman GI, Gordon JI, Hoffman HM, Flavell RA (2012) Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482(7384):179–185. doi:10.1038/nature10809

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Herfarth H, Rogler G (2005) Inflammatory bowel disease. Endoscopy 37(1):42–47. doi:10.1055/s-2004-826083

    CAS  PubMed  Google Scholar 

  76. Holler E, Landfried K, Meier J, Hausmann M, Rogler G (2010) The role of bacteria and pattern recognition receptors in GVHD. Int J Inflamm 2010:814326. doi:10.4061/2010/814326

    CAS  Google Scholar 

  77. Holler E, Rogler G, Brenmoehl J, Hahn J, Herfarth H, Greinix H, Dickinson AM, Socie G, Wolff D, Fischer G, Jackson G, Rocha V, Steiner B, Eissner G, Marienhagen J, Schoelmerich J, Andreesen R (2006) Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination. Blood 107(10):4189–4193. doi:10.1182/blood-2005-09-3741

    CAS  PubMed  Google Scholar 

  78. Holler E, Rogler G, Herfarth H, Brenmoehl J, Wild PJ, Hahn J, Eissner G, Scholmerich J, Andreesen R (2004) Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood 104(3):889–894. doi:10.1182/blood-2003-10-3543

    CAS  PubMed  Google Scholar 

  79. Hollister EB, Gao C, Versalovic J (2014) Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology 146(6):1449–1458. doi:10.1053/j.gastro.2014.01.052

    PubMed  Google Scholar 

  80. Hooper LV, Gordon JI (2001) Commensal host-bacterial relationships in the gut. Science 292(5519):1115–1118

    CAS  PubMed  Google Scholar 

  81. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI (2001) Molecular analysis of commensal host-microbial relationships in the intestine. Science 291(5505):881–884. doi:10.1126/science.291.5505.881

    CAS  PubMed  Google Scholar 

  82. Hotamisligil GS, Erbay E (2008) Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8(12):923–934. doi:10.1038/nri2449

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Huzarski T, Lener M, Domagala W, Gronwald J, Byrski T, Kurzawski G, Suchy J, Chosia M, Woyton J, Ucinski M, Narod SA, Lubinski J (2005) The 3020insC allele of NOD2 predisposes to early-onset breast cancer. Breast Cancer Res Treat 89(1):91–93. doi:10.1007/s10549-004-1250-y

    PubMed  Google Scholar 

  84. Irrazabal T, Belcheva A, Girardin SE, Martin A, Philpott DJ (2014) The multifaceted role of the intestinal microbiota in colon cancer. Mol Cell 54(2):309–320. doi:10.1016/j.molcel.2014.03.039

    CAS  PubMed  Google Scholar 

  85. Ismail AS, Hooper LV (2005) Epithelial cells and their neighbors. IV. Bacterial contributions to intestinal epithelial barrier integrity. Am J Physiol Gastrointest Liver Physiol 289(5):G779–84. doi:10.1152/ajpgi.00203.2005

    CAS  PubMed  Google Scholar 

  86. Jager S, Stange EF, Wehkamp J (2013) Inflammatory bowel disease: an impaired barrier disease. Langenbeck’s Arch Surg / Deutsche Gesellschaft fur Chirurgie 398(1):1–12. doi:10.1007/s00423-012-1030-9

    Google Scholar 

  87. Jernberg C, Lofmark S, Edlund C, Jansson JK (2010) Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 156(11):3216–3223

    CAS  PubMed  Google Scholar 

  88. Jobin C (2013) Microbial dysbiosis, a new risk factor in colorectal cancer? Med Sci : M/S 29(6–7):582–585. doi:10.1051/medsci/2013296010

    Google Scholar 

  89. Joossens M, Huys G, Cnockaert M, de Preter V, Verbeke K, Rutgeerts P, Vandamme P, Vermeire S (2011) Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60(5):631–637. doi:10.1136/gut.2010.223263

    PubMed  Google Scholar 

  90. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Buning C, Cohain A, Cichon S, D’Amato M, Jong D de, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, Vos M de, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, International, I. B. D. Genetics Consortium, Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119–124. doi:10.1038/nature11582

  91. Kallus SJ, Brandt LJ (2012) The intestinal microbiota and obesity. J Clin Gastroenterol 46(1):16–24. doi:10.1097/MCG.0b013e31823711fd

    PubMed  Google Scholar 

  92. Kang S, Denman SE, Morrison M, Yu Z, Dore J, Leclerc M, McSweeney CS (2010) Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray. Inflamm Bowel Dis 16(12):2034–2042. doi:10.1002/ibd.21319

    PubMed  Google Scholar 

  93. Kassinen A, Krogius-Kurikka L, Makivuokko H, Rinttila T, Paulin L, Corander J, Malinen E, Apajalahti J, Palva A (2007) The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 133(1):24–33. doi:10.1053/j.gastro.2007.04.005

    CAS  PubMed  Google Scholar 

  94. Khan KJ, Ullman TA, Ford AC, Abreu MT, Abadir A, Abadir A, Marshall JK, Talley NJ, Moayyedi P (2011) Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 106(4):661–673. doi:10.1038/ajg.2011.72

    CAS  PubMed  Google Scholar 

  95. Kim MS, Hwang SS, Park EJ, Bae JW (2013) Strict vegetarian diet improves the risk factors associated with metabolic diseases by modulating gut microbiota and reducing intestinal inflammation. Environ Microbiol Rep 5(5):765–775. doi:10.1111/1758-2229.12079

    CAS  PubMed  Google Scholar 

  96. Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K, Podolsky DK (1995) Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein. Gastroenterology 109(2):516–523

    CAS  PubMed  Google Scholar 

  97. Klag T, Stange EF, Wehkamp J (2013) Defective antibacterial barrier in inflammatory bowel disease. Dig Dis 31(3–4):310–316. doi:10.1159/000354858

    PubMed  Google Scholar 

  98. Kong HH, Oh J, Deming C, Conlan S, Grice EA, Beatson MA, Nomicos E, Polley EC, Komarow HD, Nisc Comparative Sequence Program, Murray PR, Turner ML, Segre JA (2012) Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome research 22(5):850–859. doi:10.1101/gr.131029.111

  99. Koren O, Spor A, Felin J, Fåk F, Stombaugh J, Tremaroli V, Behre CJ, Knight R, Fagerberg B, Ley RE, Bäckhed F (2011) Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc Natl Acad Sci U S A 108(Suppl 1):4592–4598. doi:10.1073/pnas.1011383107

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Kosovac K, Brenmoehl J, Holler E, Falk W, Schoelmerich J, Hausmann M, Rogler G (2010) Association of the NOD2 genotype with bacterial translocation via altered cell-cell contacts in Crohn’s disease patients. Inflamm Bowel Dis 16(8):1311–1321. doi:10.1002/ibd.21223

    PubMed  Google Scholar 

  101. Kostic AD, Gevers D, Pedamallu CS, Michaud M, Duke F, Earl AM, Ojesina AI, Jung J, Bass AJ, Tabernero J, Baselga J, Liu C, Shivdasani RA, Ogino S, Birren BW, Huttenhower C, Garrett WS, Meyerson M (2011) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. doi:10.1101/gr.126573.111

    PubMed  Google Scholar 

  102. Kreyenberg H, Jarisch A, Bayer C, Schuster B, Willasch A, Strahm B, Kremens B, Gruhn B, Schrauder A, Burdach S, Fuhrer M, Rossig C, Kabisch H, Schlegel PG, Stachel D, Beck JF, Mauz-Koerholz C, Chung TL, Holler E, Klingebiel T, Bader P (2011) NOD2/CARD15 gene polymorphisms affect outcome in pediatric allogeneic stem cell transplantation. Blood 118(4):1181–1184. doi:10.1182/blood-2011-05-356451

    CAS  PubMed  Google Scholar 

  103. Kump PK, Grochenig HP, Lackner S, Trajanoski S, Reicht G, Hoffmann KM, Deutschmann A, Wenzl HH, Petritsch W, Krejs GJ, Gorkiewicz G, Hogenauer C (2013) Alteration of intestinal dysbiosis by fecal microbiota transplantation does not induce remission in patients with chronic active ulcerative colitis. Inflamm Bowel Dis 19(10):2155–2165. doi:10.1097/MIB.0b013e31829ea325

    PubMed  Google Scholar 

  104. Lakatos PL, Hitre E, Szalay F, Zinober K, Fuszek P, Lakatos L, Fischer S, Osztovits J, Gemela O, Veres G, Papp J, Ferenci P (2007) Common NOD2/CARD15 variants are not associated with susceptibility or the clinicopathologic characteristics of sporadic colorectal cancer in Hungarian patients. BMC Cancer 7:54. doi:10.1186/1471-2407-7-54

    PubMed Central  PubMed  Google Scholar 

  105. Landfried K, Bataille F, Rogler G, Brenmoehl J, Kosovac K, Wolff D, Hilgendorf I, Hahn J, Edinger M, Hoffmann P, Obermeier F, Schoelmerich J, Andreesen R, Holler E (2010) Recipient NOD2/CARD15 status affects cellular infiltrates in human intestinal graft-versus-host disease. Clin Exp Immunol 159(1):87–92. doi:10.1111/j.1365-2249.2009.04049.x

    CAS  PubMed Central  PubMed  Google Scholar 

  106. le Poul E, Loison C, Struyf S, Springael J, Lannoy V, Decobecq M, Brezillon S, Dupriez V, Vassart G, van Damme J, Parmentier M, Detheux M (2003) Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem 278(28):25481–25489. doi:10.1074/jbc.M301403200

    PubMed  Google Scholar 

  107. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2012) The association between the PTPN22 C1858T polymorphism and rheumatoid arthritis. A meta-analysis update. Mol Biol Rep 39(4):3453–3460. doi:10.1007/s11033-011-1117-3

    CAS  PubMed  Google Scholar 

  108. Lee YK, Mazmanian SK (2010) Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330(6012):1768–1773. doi:10.1126/science.1195568

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Lees CW, Barrett JC, Parkes M, Satsangi J (2011) New IBD genetics: common pathways with other diseases. Gut 60(12):1739–1753. doi:10.1136/gut.2009.199679

    CAS  PubMed  Google Scholar 

  110. Lees CW, Satsangi J (2009) Genetics of inflammatory bowel disease: implications for disease pathogenesis and natural history. Exp Rev Gastroenterol Hepatol 3(5):513–534. doi:10.1586/egh.09.45

    CAS  Google Scholar 

  111. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102(31):11070–11075. doi:10.1073/pnas.0504978102

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Ley RE, Peterson DA, Gordon JI (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124(4):837–848. doi:10.1016/j.cell.2006.02.017

    CAS  PubMed  Google Scholar 

  113. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444(7122):1022–1023. doi:10.1038/4441022a

    CAS  PubMed  Google Scholar 

  114. Liu J, He C, Xu Q, Xing C, Yuan Y (2014) NOD2 polymorphisms associated with cancer risk: a meta-analysis. PLoS One 9(2):e89340. doi:10.1371/journal.pone.0089340

    PubMed Central  PubMed  Google Scholar 

  115. Louis P (2012) Does the human gut microbiota contribute to the etiology of autism spectrum disorders? Dig Dis Sci 57(8):1987–1989. doi:10.1007/s10620-012-2286-1

    PubMed  Google Scholar 

  116. Louis E, Michel V, Hugot JP, Reenaers C, Fontaine F, Delforge M, el Yafi F, Colombel JF, Belaiche J (2003) Early development of stricturing or penetrating pattern in Crohn’s disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype. Gut 52(4):552–557

    CAS  PubMed Central  PubMed  Google Scholar 

  117. Lozupone CA, Knight R (2008) Species divergence and the measurement of microbial diversity. FEMS Microbiol Rev 32(4):557–578. doi:10.1111/j.1574-6976.2008.00111.x

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Lubinski J, Huzarski T, Kurzawski G, Suchy J, Masojc B, Mierzejewski M, Lener M, Domagala W, Chosia M, Teodorczyk U, Medrek K, Debniak T, Zlowocka E, Gronwald J, Byrski T, Grabowska E, Nej K, Szymanska A, Szymanska J, Matyjasik J, Cybulski C, Jakubowska A, Gorski B, Narod SA (2005) The 3020insC Allele of NOD2 predisposes to cancers of multiple organs. Hereditary Cancer Clin Pract 3(2):59–63. doi:10.1186/1897-4287-3-2-59

    CAS  Google Scholar 

  119. Machiels K, Joossens M, Sabino J, de Preter V, Arijs I, Eeckhaut V, Ballet V, Claes K, van Immerseel F, Verbeke K, Ferrante M, Verhaegen J, Rutgeerts P, Vermeire S (2013) A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut. doi:10.1136/gutjnl-2013-304833

    Google Scholar 

  120. Makivuokko H, Tiihonen K, Tynkkynen S, Paulin L, Rautonen N (2010) The effect of age and non-steroidal anti-inflammatory drugs on human intestinal microbiota composition. Br J Nutr 103(2):227–234. doi:10.1017/S0007114509991553

    PubMed  Google Scholar 

  121. Marchiando AM, Shen L, Graham WV, Edelblum KL, Duckworth CA, Guan Y, Montrose MH, Turner JR, Watson AJ (2011) The epithelial barrier is maintained by in vivo tight junction expansion during pathologic intestinal epithelial shedding. Gastroenterology 140(4):1208–1218. doi:10.1053/j.gastro.2011.01.004, e1-2

    CAS  PubMed Central  PubMed  Google Scholar 

  122. Mariat D, Firmesse O, Levenez F, Guimaraes V, Sokol H, Dore J, Corthier G, Furet JP (2009) The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol 9:123. doi:10.1186/1471-2180-9-123

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Martinez-Medina M, Denizot J, Dreux N, Robin F, Billard E, Bonnet R, Darfeuille-Michaud A, Barnich N (2014) Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut 63(1):116–124. doi:10.1136/gutjnl-2012-304119

    PubMed  Google Scholar 

  124. Matias Rodrigues JF, von Mering C (2014) HPC-CLUST: distributed hierarchical clustering for large sets of nucleotide sequences. Bioinformatics 30(2):287–288. doi:10.1093/bioinformatics/btt657

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Mattos-Guaraldi AL, Duarte Formiga LC, Pereira GA (2000) Cell surface components and adhesion in Corynebacterium diphtheriae. Microbes Infect / Institut Pasteur 2(12):1507–1512

    CAS  Google Scholar 

  126. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL (2005) An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell 122(1):107–118. doi:10.1016/j.cell.2005.05.007

    CAS  PubMed  Google Scholar 

  127. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142(1):46–54. doi:10.1053/j.gastro.2011.10.001, e42; quiz e30

    PubMed  Google Scholar 

  128. Mondot S, de Wouters T, Dore J, Lepage P (2013) The human gut microbiome and its dysfunctions. Dig Dis 31(3–4):278–285. doi:10.1159/000354678

    PubMed  Google Scholar 

  129. Mutlu E, Keshavarzian A, Engen P, Forsyth CB, Sikaroodi M, Gillevet P (2009) Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. Alcohol Clin Exp Res 33(10):1836–1846. doi:10.1111/j.1530-0277.2009.01022.x

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Naseribafrouei A, Hestad K, Avershina E, Sekelja M, Linlokken A, Wilson R, Rudi K (2014) Correlation between the human fecal microbiota and depression. Neurogastroenterol Motil : Off J Eur Gastrointest Motil Soc. doi:10.1111/nmo.12378

    Google Scholar 

  131. Naumann M, Rudel T, Meyer TF (1999) Host cell interactions and signalling with Neisseria gonorrhoeae. Curr Opin Microbiol 2(1):62–70

    CAS  PubMed  Google Scholar 

  132. Nielsen S, Nielsen DS, Lauritzen L, Jakobsen M, Michaelsen KF (2007) Impact of diet on the intestinal microbiota in 10-month-old infants. J Pediatr Gastroenterol Nutr 44(5):613–618. doi:10.1097/MPG.0b013e3180406a11

    CAS  PubMed  Google Scholar 

  133. Nylund L, Satokari R, Nikkila J, Rajilic-Stojanovic M, Kalliomaki M, Isolauri E, Salminen S, de Vos WM (2013) Microarray analysis reveals marked intestinal microbiota aberrancy in infants having eczema compared to healthy children in at-risk for atopic disease. BMC Microbiol 13:12. doi:10.1186/1471-2180-13-12

    PubMed Central  PubMed  Google Scholar 

  134. O’Hara P, Connett JE, Lee WW, Nides M, Murray R, Wise R (1998) Early and late weight gain following smoking cessation in the Lung Health Study. Am J Epidemiol 148(9):821–830

    PubMed  Google Scholar 

  135. O’Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, Cryan JF, Dinan TG (2009) Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65(3):263–267. doi:10.1016/j.biopsych.2008.06.026

    PubMed  Google Scholar 

  136. Ohland CL, Macnaughton WK (2010) Probiotic bacteria and intestinal epithelial barrier function. American journal of physiology. Gastrointes Liver Physiol 298(6):G807–19. doi:10.1152/ajpgi.00243.2009

    CAS  Google Scholar 

  137. Olivares M, Laparra JM, Sanz Y (2013) Host genotype, intestinal microbiota and inflammatory disorders. Br J Nutr 109(Suppl 2):S76–80. doi:10.1017/S0007114512005521

    CAS  PubMed  Google Scholar 

  138. Ostaff MJ, Stange EF, Wehkamp J (2013) Antimicrobial peptides and gut microbiota in homeostasis and pathology. EMBO Mol Med 5(10):1465–1483. doi:10.1002/emmm.201201773

    CAS  PubMed Central  PubMed  Google Scholar 

  139. Packey CD, Sartor RB (2009) Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr Opin Infect Dis 22(3):292–301. doi:10.1097/QCO.0b013e32832a8a5d

    PubMed Central  PubMed  Google Scholar 

  140. Park AJ, Collins J, Blennerhassett PA, Ghia JE, Verdu EF, Bercik P, Collins SM (2013) Altered colonic function and microbiota profile in a mouse model of chronic depression. Neurogastroenterol Motil : Off J Eur Gastrointest Motil Soc 25(9):733–e575. doi:10.1111/nmo.12153

    CAS  Google Scholar 

  141. Patti JM, Hook M (1994) Microbial adhesins recognizing extracellular matrix macromolecules. Curr Opin Cell Biol 6(5):752–758

    CAS  PubMed  Google Scholar 

  142. Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, Hamelmann E (2013) Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clinical Immunol 132(3):601–607. doi:10.1016/j.jaci.2013.05.043, e8

    Google Scholar 

  143. Penders J, Gerhold K, Thijs C, Zimmermann K, Wahn U, Lau S, Hamelmann E (2014) New insights into the hygiene hypothesis in allergic diseases: mediation of sibling and birth mode effects by the gut microbiota. Gut Microbes 5(2):239–244. doi:10.4161/gmic.27905

    PubMed  Google Scholar 

  144. Penders J, Stobberingh EE, Thijs C, Adams H, Vink C, van Ree R, van den Brandt PA (2006) Molecular fingerprinting of the intestinal microbiota of infants in whom atopic eczema was or was not developing. Clin Exp Allergy : J Br Soc Allergy Clin Immunol 36(12):1602–1608. doi:10.1111/j.1365-2222.2006.02599.x

    CAS  Google Scholar 

  145. Penders J, Stobberingh EE, van den Brandt PA, Thijs C (2007) The role of the intestinal microbiota in the development of atopic disorders. Allergy 62(11):1223–1236. doi:10.1111/j.1398-9995.2007.01462.x

    CAS  PubMed  Google Scholar 

  146. Peterson LW, Artis D (2014) Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol 14(3):141–153. doi:10.1038/nri3608

    CAS  PubMed  Google Scholar 

  147. Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP (2011) Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 364(1):22–32

    CAS  PubMed  Google Scholar 

  148. Power SE, O’Toole PW, Stanton C, Ross RP, Fitzgerald GF (2014) Intestinal microbiota, diet and health. Br J Nutr 111(3):387–402. doi:10.1017/S0007114513002560

    CAS  PubMed  Google Scholar 

  149. Radon K, Windstetter D, Poluda AL, Mueller B, von Mutius E, Koletzko S (2007) Contact with farm animals in early life and juvenile inflammatory bowel disease: a case–control study. Pediatrics 120(2):354–361. doi:10.1542/peds. 2006-3624

    PubMed  Google Scholar 

  150. Rajilic-Stojanovic M, Biagi E, Heilig HG, Kajander K, Kekkonen RA, Tims S, de Vos WM (2011) Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 141(5):1792–1801. doi:10.1053/j.gastro.2011.07.043

    CAS  PubMed  Google Scholar 

  151. Rajilic-Stojanovic M, Shanahan F, Guarner F, de Vos WM (2013) Phylogenetic analysis of dysbiosis in ulcerative colitis during remission. Inflamm Bowel Dis 19(3):481–488. doi:10.1097/MIB.0b013e31827fec6d

    PubMed  Google Scholar 

  152. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ (2011) Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 108(Suppl 1):4680–4687. doi:10.1073/pnas.1002611107

    CAS  PubMed Central  PubMed  Google Scholar 

  153. Rehman A, Sina C, Gavrilova O, Hasler R, Ott S, Baines JF, Schreiber S, Rosenstiel P (2011) Nod2 is essential for temporal development of intestinal microbial communities. Gut 60(10):1354–1362. doi:10.1136/gut.2010.216259

    CAS  PubMed  Google Scholar 

  154. Rescigno M (2014) Intestinal microbiota and its effects on the immune system. Cell Microbiol. doi:10.1111/cmi.12301

    PubMed  Google Scholar 

  155. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, Gordon JI (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341(6150):1241214. doi:10.1126/science.1241214

    PubMed  Google Scholar 

  156. Rinttila T, Lyra A, Krogius-Kurikka L, Palva A (2011) Real-time PCR analysis of enteric pathogens from fecal samples of irritable bowel syndrome subjects. Gut Pathog 3(1):6. doi:10.1186/1757-4749-3-6

    CAS  PubMed Central  PubMed  Google Scholar 

  157. Rogers CJ, Prabhu KS, Vijay-Kumar M (2014) The microbiome and obesity-an established risk for certain types of cancer. Cancer J 20(3):176–180. doi:10.1097/PPO.0000000000000049

    CAS  PubMed  Google Scholar 

  158. Rogler G (2011) Interaction between susceptibility and environment. Examples from the digestive tract. Dig Dis 29(2):136–143. doi:10.1159/000323876

    PubMed  Google Scholar 

  159. Rogler G, Holler E (2004) Can NOD2/CARD15 mutations predict intestinal graft-versus-host disease and aid our understanding of Crohn’s disease? Nat Clin Pract Gastroenterol Hepatol 1(2):62–63. doi:10.1038/ncpgasthep0042

    PubMed  Google Scholar 

  160. Rogler G, Rosano G (2014) The heart and the gut. Eur Heart J 35(7):426–430. doi:10.1093/eurheartj/eht271

    PubMed  Google Scholar 

  161. Sakata S, Tonooka T, Ishizeki S, Takada M, Sakamoto M, Fukuyama M, Benno Y (2005) Culture-independent analysis of fecal microbiota in infants, with special reference to Bifidobacterium species. FEMS Microbiol Lett 243(2):417–423. doi:10.1016/j.femsle.2005.01.002

    CAS  PubMed  Google Scholar 

  162. Salonen A, de Vos WM (2014) Impact of diet on human intestinal microbiota and health. Annu Rev Food Sci Technol 5:239–262. doi:10.1146/annurev-food-030212-182554

    CAS  PubMed  Google Scholar 

  163. Salonen A, Lahti L, Salojarvi J, Holtrop G, Korpela K, Duncan SH, Date P, Farquharson F, Johnstone AM, Lobley GE, Louis P, Flint HJ, de Vos WM (2014) Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men. ISME J. doi:10.1038/ismej.2014.63

    PubMed  Google Scholar 

  164. Santacruz A, Marcos A, Wärnberg J, Martí A, Martin-Matillas M, Campoy C, Moreno LA, Veiga O, Redondo-Figuero C, Garagorri JM, Azcona C, Delgado M, García-Fuentes M, Collado MC, Sanz Y (2009) Interplay between weight loss and gut microbiota composition in overweight adolescents. Obesity (Silver Spring) 17(10):1906–1915. doi:10.1038/oby.2009.112

    Google Scholar 

  165. Saulnier DM, Riehle K, Mistretta TA, Diaz MA, Mandal D, Raza S, Weidler EM, Qin X, Coarfa C, Milosavljevic A, Petrosino JF, Highlander S, Gibbs R, Lynch SV, Shulman RJ, Versalovic J (2011) Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology 141(5):1782–1791. doi:10.1053/j.gastro.2011.06.072

    CAS  PubMed Central  PubMed  Google Scholar 

  166. Savage DC (1977) Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 31:107–133. doi:10.1146/annurev.mi.31.100177.000543

    CAS  PubMed  Google Scholar 

  167. Scanlan PD, Shanahan F, Clune Y, Collins JK, O’Sullivan GC, O’Riordan M, Holmes E, Wang Y, Marchesi JR (2008) Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol 10(3):789–798. doi:10.1111/j.1462-2920.2007.01503.x

    CAS  PubMed  Google Scholar 

  168. Scanlan PD, Shanahan F, O’Mahony C, Marchesi JR (2006) Culture-independent analyses of temporal variation of the dominant fecal microbiota and targeted bacterial subgroups in Crohn’s disease. J Clin Microbiol 44(11):3980–3988. doi:10.1128/JCM. 00312-06

    CAS  PubMed Central  PubMed  Google Scholar 

  169. Scharl M, Rogler G (2012) Inflammatory bowel disease pathogenesis. What is new? Curr Opin Gastroenterol 28(4):301–309. doi:10.1097/MOG.0b013e328353e61e

    PubMed  Google Scholar 

  170. Scher JU, Abramson SB (2011) The microbiome and rheumatoid arthritis. Nat Rev Rheumatol 7(10):569–578. doi:10.1038/nrrheum.2011.121

    CAS  PubMed Central  PubMed  Google Scholar 

  171. Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, Buchner J, Schaller M, Stange EF, Wehkamp J (2011) Reduction of disulphide bonds unmasks potent antimicrobial activity of human beta-defensin 1. Nature 469(7330):419–423. doi:10.1038/nature09674

    CAS  PubMed  Google Scholar 

  172. Schwabe RF, Jobin C (2013) The microbiome and cancer. Nat Rev Cancer 13(11):800–812. doi:10.1038/nrc3610

    CAS  PubMed Central  PubMed  Google Scholar 

  173. Seksik P, Rigottier-Gois L, Gramet G, Sutren M, Pochart P, Marteau P, Jian R, Dore J (2003) Alterations of the dominant faecal bacterial groups in patients with Crohn’s disease of the colon. Gut 52(2):237–242

    CAS  PubMed Central  PubMed  Google Scholar 

  174. Shackel NA, Vadas MA, Gamble JR, McCaughan GW (2014) Beyond liver fibrosis. Hepatic stellate cell senescence links obesity to liver cancer by way of the microbiome. Hepatology 59(6):2413–2415. doi:10.1002/hep.26932

    CAS  PubMed  Google Scholar 

  175. Shaw SY, Blanchard JF, Bernstein CN (2011) Association between the use of antibiotics and new diagnoses of Crohn’s disease and ulcerative colitis. Am J Gastroenterol 106(12):2133–2142. doi:10.1038/ajg.2011.304

    PubMed  Google Scholar 

  176. Shen W, Gaskins HR, McIntosh MK (2014) Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes. J Nutr Biochem 25(3):270–280. doi:10.1016/j.jnutbio.2013.09.009

    CAS  PubMed  Google Scholar 

  177. Singh S, Nagpal SJS, Murad MH, Yadav S, Kane SV, Pardi DS, Talwalkar JA, Loftus EV (2014) Inflammatory bowel disease is associated with an increased risk of melanoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 12(2):210–218

    PubMed  Google Scholar 

  178. Slack E, Hapfelmeier S, Stecher B, Velykoredko Y, Stoel M, Lawson MA, Geuking MB, Beutler B, Tedder TF, Hardt WD, Bercik P, Verdu EF, McCoy KD, Macpherson AJ (2009) Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. Science 325(5940):617–620. doi:10.1126/science.1172747

    CAS  PubMed Central  PubMed  Google Scholar 

  179. Smith MI, Yatsunenko T, Manary MJ, Trehan I, Mkakosya R, Cheng J, Kau AL, Rich SS, Concannon P, Mychaleckyj JC, Liu J, Houpt E, Li JV, Holmes E, Nicholson J, Knights D, Ursell LK, Knight R, Gordon JI (2013) Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339(6119):548–554. doi:10.1126/science.1229000

    CAS  PubMed Central  PubMed  Google Scholar 

  180. Stamler J, Rains-Clearman D, Lenz-Litzow K, Tillotson JL, Grandits GA (1997) Relation of smoking at baseline and during trial years 1–6 to food and nutrient intakes and weight in the special intervention and usual care groups in the multiple risk factor intervention trial. Am J Clin Nutr 65(1 Suppl):374S–402S

    CAS  PubMed  Google Scholar 

  181. Stappenbeck TS, Hooper LV, Gordon JI (2002) Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A 99(24):15451–15455. doi:10.1073/pnas.202604299

    CAS  PubMed Central  PubMed  Google Scholar 

  182. Stecher B, Macpherson AJ, Hapfelmeier S, Kremer M, Stallmach T, Hardt WD (2005) Comparison of Salmonella enterica serovar Typhimurium colitis in germfree mice and mice pretreated with streptomycin. Infect Immun 73(6):3228–3241. doi:10.1128/IAI. 73.6.3228-3241.2005

    CAS  PubMed Central  PubMed  Google Scholar 

  183. Sun L, Nava GM, Stappenbeck TS (2011) Host genetic susceptibility, dysbiosis, and viral triggers in inflammatory bowel disease. Curr Opin Gastroenterol 27(4):321–327. doi:10.1097/MOG.0b013e32834661b4

    PubMed Central  PubMed  Google Scholar 

  184. Svanborg C, Hedlund M, Connell H, Agace W, Duan RD, Nilsson A, Wullt B (1996) Bacterial adherence and mucosal cytokine responses. Receptors and transmembrane signaling. Ann N Y Acad Sci 797:177–190

    CAS  PubMed  Google Scholar 

  185. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, Weber J, Hoffmann U, Schreiber S, Dietel M, Lochs H (2002) Mucosal flora in inflammatory bowel disease. Gastroenterology 122(1):44–54

    PubMed  Google Scholar 

  186. Swidsinski A, Loening-Baucke V, Lochs H, Hale LP (2005) Spatial organization of bacterial flora in normal and inflamed intestine. a fluorescence in situ hybridization study in mice. World J Gastroenterol : WJG 11(8):1131–1140

    PubMed Central  PubMed  Google Scholar 

  187. Swidsinski A, Loening-Baucke V, Herber A (2009) Mucosal flora in Crohn’s disease and ulcerative colitis - an overview. J Physiol Pharmacol : Off J Pol Physiol Soc 60(Suppl 6):61–71

    Google Scholar 

  188. Tanaka S, Kobayashi T, Songjinda P, Tateyama A, Tsubouchi M, Kiyohara C, Shirakawa T, Sonomoto K, Nakayama J (2009) Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunol Med Microbiol 56(1):80–87. doi:10.1111/j.1574-695X.2009.00553.x

    CAS  PubMed  Google Scholar 

  189. Tilg H (2010) Obesity, metabolic syndrome, and microbiota. multiple interactions. J Clin Gastroenterol 44(Suppl 1):S16–8. doi:10.1097/MCG.0b013e3181dd8b64

    CAS  PubMed  Google Scholar 

  190. Tillisch K, Labus J, Kilpatrick L, Jiang Z, Stains J, Ebrat B, Guyonnet D, Legrain–Raspaud S, Trotin B, Naliboff B, Mayer EA (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144(7):1394–1401, e4

    CAS  PubMed  Google Scholar 

  191. Tomasini-Johansson BR, Kaufman NR, Ensenberger MG, Ozeri V, Hanski E, Mosher DF (2001) A 49-residue peptide from adhesin F1 of Streptococcus pyogenes inhibits fibronectin matrix assembly. J Biol Chem 276(26):23430–23439. doi:10.1074/jbc.M103467200

    CAS  PubMed  Google Scholar 

  192. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI (2006) An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444(7122):1027–1031. doi:10.1038/nature05414

    PubMed  Google Scholar 

  193. Turner JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9(11):799–809. doi:10.1038/nri2653

    CAS  PubMed  Google Scholar 

  194. Tuupanen S, Alhopuro P, Mecklin JP, Jarvinen H, Aaltonen LA (2007) No evidence for association of NOD2 R702W and G908R with colorectal cancer. International journal of cancer. J Int Cancer 121(1):76–79. doi:10.1002/ijc.22651

    CAS  Google Scholar 

  195. Ursell LK, Haiser HJ, van Treuren W, Garg N, Reddivari L, Vanamala J, Dorrestein PC, Turnbaugh PJ, Knight R (2014) The intestinal metabolome: an intersection between microbiota and host. Gastroenterology 146(6):1470–1476. doi:10.1053/j.gastro.2014.03.001

    CAS  PubMed  Google Scholar 

  196. Vaahtovuo J, Munukka E, Korkeamäki M, Luukkainen R, Toivanen P (2008) Fecal microbiota in early rheumatoid arthritis. J Rheumatol 35(8):1500–1505

    CAS  PubMed  Google Scholar 

  197. Ventura M, Turroni F, Motherway MO, MacSharry J, van Sinderen D (2012) Host-microbe interactions that facilitate gut colonization by commensal bifidobacteria. Trends Microbiol 20(10):467–476. doi:10.1016/j.tim.2012.07.002

    CAS  PubMed  Google Scholar 

  198. Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Berard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Dore J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L (2013) The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 342(6161):971–976. doi:10.1126/science.1240537

    CAS  PubMed Central  PubMed  Google Scholar 

  199. Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, Sitaraman SV, Knight R, Ley RE, Gewirtz AT (2010) Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328(5975):228–231. doi:10.1126/science.1179721

    CAS  PubMed  Google Scholar 

  200. Vrieze A, van Nood E, Holleman F, Salojarvi J, Kootte RS, Bartelsman JF, Dallinga-Thie GM, Ackermans MT, Serlie MJ, Oozeer R, Derrien M, Druesne A, van Hylckama Vlieg JE, Bloks VW, Groen AK, Heilig HG, Zoetendal EG, Stroes ES, de Vos WM, Hoekstra JB, Nieuwdorp M (2012) Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology 143(4):913–6. doi:10.1053/j.gastro.2012.06.031, e7

    CAS  PubMed  Google Scholar 

  201. Walter J, Ley R (2011) The human gut microbiome: ecology and recent evolutionary changes. Annu Rev Microbiol 65:411–429. doi:10.1146/annurev-micro-090110-102830

    CAS  PubMed  Google Scholar 

  202. Wang L, Conlon MA, Christophersen CT, Sorich MJ, Angley MT (2014) Gastrointestinal microbiota and metabolite biomarkers in children with autism spectrum disorders. Biomark Med 8(3):331–344. doi:10.2217/bmm.14.12

    PubMed  Google Scholar 

  203. Wang P, Zhang L, Jiang JM, Ma D, Tao HX, Yuan SL, Wang YC, Wang LC, Liang H, Zhang ZS, Liu CJ (2012) Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population. World J Gastroenterol : WJG 18(17):2112–2120. doi:10.3748/wjg.v18.i17.2112

    CAS  PubMed Central  PubMed  Google Scholar 

  204. Ward ME, Watt PJ (1972) Adherence of Neisseria gonorrhoeae to urethral mucosal cells: an electron-microscopic study of human gonorrhea. J Infect Dis 126(6):601–605

    CAS  PubMed  Google Scholar 

  205. Watson AJ, Chu S, Sieck L, Gerasimenko O, Bullen T, Campbell F, McKenna M, Rose T, Montrose MH (2005) Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology 129(3):902–912. doi:10.1053/j.gastro.2005.06.015

    PubMed  Google Scholar 

  206. Watson AJ, Hughes KR (2012) TNF-alpha-induced intestinal epithelial cell shedding: implications for intestinal barrier function. Ann N Y Acad Sci 1258:1–8. doi:10.1111/j.1749-6632.2012.06523.x

    CAS  PubMed  Google Scholar 

  207. Wehkamp J, Koslowski M, Wang G, Stange EF (2008) Barrier dysfunction due to distinct defensin deficiencies in small intestinal and colonic Crohn’s disease. Mucosal Immunol 1(Suppl 1):S67–74. doi:10.1038/mi.2008.48

    CAS  PubMed  Google Scholar 

  208. Wehkamp J, Stange EF (2006) A new look at Crohn’s disease: breakdown of the mucosal antibacterial defense. Ann N Y Acad Sci 1072:321–331. doi:10.1196/annals.1326.030

    CAS  PubMed  Google Scholar 

  209. Wen L, Ley RE, Volchkov PY, Stranges PB, Avanesyan L, Stonebraker AC, Hu C, Wong FS, Szot GL, Bluestone JA, Gordon JI, Chervonsky AV (2008) Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455(7216):1109–1113. doi:10.1038/nature07336

    CAS  PubMed Central  PubMed  Google Scholar 

  210. Wijburg OL, Uren TK, Simpfendorfer K, Johansen FE, Brandtzaeg P, Strugnell RA (2006) Innate secretory antibodies protect against natural Salmonella typhimurium infection. J Exp Med 203(1):21–26. doi:10.1084/jem.20052093

    CAS  PubMed Central  PubMed  Google Scholar 

  211. Wold AE, Thorssen M, Hull S, Eden CS (1988) Attachment of Escherichia coli via mannose- or Gal alpha 1–4Gal beta-containing receptors to human colonic epithelial cells. Infect Immun 56(10):2531–2537

    CAS  PubMed Central  PubMed  Google Scholar 

  212. Wood NJ (2012) Microbiota: dysbiosis driven by inflammasome deficiency exacerbates hepatic steatosis and governs rate of NAFLD progression. Nat Rev Gastroenterol Hepatol 9(3):123. doi:10.1038/nrgastro.2012.21

    PubMed  Google Scholar 

  213. Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI (2012) Human gut microbiome viewed across age and geography. Nature 486(7402):222–227. doi:10.1038/nature11053

    CAS  PubMed Central  PubMed  Google Scholar 

  214. Young D, Hussell T, Dougan G (2002) Chronic bacterial infections: living with unwanted guests. Nat Immunol 3(11):1026–1032. doi:10.1038/ni1102-1026

    CAS  PubMed  Google Scholar 

  215. Zoetendal EG, de Vos WM (2014) Effect of diet on the intestinal microbiota and its activity. Curr Opin Gastroenterol 30(2):189–195. doi:10.1097/MOG.0000000000000048

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gerhard Rogler.

Additional information

Communicated by Beat Steinmann

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Biedermann, L., Rogler, G. The intestinal microbiota: its role in health and disease. Eur J Pediatr 174, 151–167 (2015). https://doi.org/10.1007/s00431-014-2476-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-014-2476-2

Keywords

Navigation