Gastroenterology
Volume 141, Issue 5 , Pages 1782-1791 , November 2011

Gastrointestinal Microbiome Signatures of Pediatric Patients With Irritable Bowel Syndrome

  • Delphine M. Saulnier

      Affiliations

    • Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
    • Department of Pathology, Texas Children's Hospital, Houston, Texas
    • NIZO, Ede, The Netherlands
    • ,
  • Kevin Riehle

      Affiliations

    • Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas
    • Bioinformatics Research Laboratory, Baylor College of Medicine, Houston, Texas
    • ,
  • Toni–Ann Mistretta

      Affiliations

    • Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
    • Department of Pathology, Texas Children's Hospital, Houston, Texas
    • ,
  • Maria–Alejandra Diaz

      Affiliations

    • Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
    • Department of Pathology, Texas Children's Hospital, Houston, Texas
    • ,
  • Debasmita Mandal

      Affiliations

    • Department of Medicine, University of California San Francisco, San Francisco, California
    • ,
  • Sabeen Raza

      Affiliations

    • Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
    • Department of Pathology, Texas Children's Hospital, Houston, Texas
    • ,
  • Erica M. Weidler

      Affiliations

    • Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    • Children's Nutrition Research Center, Houston, Texas
    • ,
  • Xiang Qin

      Affiliations

    • Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
    • ,
  • Cristian Coarfa

      Affiliations

    • Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas
    • Bioinformatics Research Laboratory, Baylor College of Medicine, Houston, Texas
    • ,
  • Aleksandar Milosavljevic

      Affiliations

    • Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas
    • Bioinformatics Research Laboratory, Baylor College of Medicine, Houston, Texas
    • ,
  • Joseph F. Petrosino

      Affiliations

    • Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
    • Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas
    • Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas
    • ,
  • Sarah Highlander

      Affiliations

    • Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
    • Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas
    • ,
  • Richard Gibbs

      Affiliations

    • Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas
    • ,
  • Susan V. Lynch

      Affiliations

    • Department of Medicine, University of California San Francisco, San Francisco, California
    • ,
  • Robert J. Shulman

      Affiliations

    • Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    • Children's Nutrition Research Center, Houston, Texas
    • ,
  • James Versalovic

      Affiliations

    • Departments of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
    • Department of Pathology, Texas Children's Hospital, Houston, Texas
    • Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas
    • Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    • Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas
    • Corresponding Author InformationReprint requests Address requests for reprints to: James Versalovic, MD, PhD, Texas Children's Hospital Feigin Center, 1102 Bates Avenue, Suite 830, Feigin Center, Houston, Texas 77030. fax: (832) 825-1165

Received 21 January 2011 ,Accepted 24 June 2011.

References 

  1. Apley J . The child with abdominal pains . Philadelphia, PA: Blackwell Scientific; 1975;
  2. Zuckerman B , Stevenson J , Bailey V . Stomachaches and headaches in a community sample of preschool children . Pediatrics . 1987;79:677–682
  3. Miele E , Simeone D , Marino A , et al.   Functional gastrointestinal disorders in children: an Italian prospective survey . Pediatrics . 2004;114:73–78
  4. Thakkar K , Gilger MA , Shulman RJ , et al.   EGD in children with abdominal pain: a systematic review . Am J Gastroenterol . 2007;102:654–661
  5. Saps M , Sztainberg M , Di Lorenzo C . A prospective community-based study of gastroenterological symptoms in school-age children . J Pediatr Gastroenterol Nutr . 2006;43:477–482
  6. Uc A , Hyman PE , Walker LS . Functional gastrointestinal disorders in African American children in primary care . J Pediatr Gastroenterol Nutr . 2006;42:270–274
  7. Rasquin A , Di Lorenzo C , Forbes D , et al.   Childhood functional gastrointestinal disorders: child/adolescent . Gastroenterology . 2006;130:1527–1537
  8. Longstreth GF , Thompson WG , Chey WD , et al.   Functional bowel disorders . Gastroenterology . 2006;130:1480–1491
  9. Shulman RJ , Eakin MN , Jarrett M , et al.   Characteristics of pain and stooling in children with recurrent abdominal pain . J Pediatr Gastroenterol Nutr . 2007;44:203–208
  10. Walker LS , Guite JW , Duke M , et al.   Recurrent abdominal pain: a potential precursor of irritable bowel syndrome in adolescents and young adults . J Pediatr . 1998;132:1010–1015
  11. Jarrett M , Heitkemper M , Czyzewski DI , et al.   Recurrent abdominal pain in children: forerunner to adult irritable bowel syndrome? . J Spec Pediatr Nurs . 2003;8:81–89
  12. Scharff L . Recurrent abdominal pain in children: a review of psychological factors and treatment . Clin Psychol Rev . 1997;17:145–166
  13. Salonen A , de Vos WM , Palva A . Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives . Microbiology . 2010;156:3205–3215
  14. Malinen E , Rinttila T , Kajander K , et al.   Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR . Am J Gastroenterol . 2005;100:373–382
  15. Verdu EF , Bercik P , Verma-Gandhu M , et al.   Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice . Gut . 2006;55:182–190
  16. Lyra A , Krogius-Kurikka L , Nikkila J , et al.   Effect of a multispecies probiotic supplement on quantity of irritable bowel syndrome-related intestinal microbial phylotypes . BMC Gastroenterol . 2010;10:110
  17. Moayyedi P , Ford AC , Talley NJ , et al.   The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review . Gut . 2010;59:325–332
  18. Spiller P . Review article: probiotics and prebiotics in irritable bowel syndrome (IBS) . Aliment Pharmacol Ther . 2008;28:385–396
  19. Francavilla R , Miniello V , Magista AM , et al.   A randomized controlled trial of Lactobacillus GG in children with functional abdominal pain . Pediatrics . 2010;126:e1445–e1452
  20. Breiman L . Random forests . Mach Learn . 2001;45:5–32
  21. Chumpitazi BP , Lane MM , Czyzewski DI , et al.   Creation and initial evaluation of a Stool Form Scale for children . J Pediatr . 2010;157:594–597
  22. von Baeyer CL , Spagrud LJ , McCormick JC , et al.   Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for children's self-reports of pain intensity . Pain . 2009;143:223–227
  23. Lewis SJ , Heaton KW . Stool form scale as a useful guide to intestinal transit time . Scand J Gastroenterol . 1997;32:920–924
  24. Cole JR , Wang Q , Cardenas E , et al.   The Ribosomal Database Project: improved alignments and new tools for rRNA analysis . Nucleic Acids Res . 2009;37:D141–D145
  25. Caporaso JG , Kuczynski J , Stombaugh J , et al.   QIIME allows analysis of high-throughput community sequencing data . Nat Methods . 2010;7:335–336
  26. Whittaker RH . Evolution and measurement of species diversity . Taxon . 1972;21:213–251
  27. Liaw A , Wiener M . Classification and regression by randomForest . R news . 2002;2:18–22
  28. Kursa MB , Rudnicki WR . Feature selection with the Boruta package . J Stat Softw . 2010;36:1–13
  29. Cox MJ , Huang YJ , Fujimura KE , et al.   Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome . PLoS One . 2010;5:e8745
  30. Yergeau E , Schoondermark-Stolk SA , Brodie EL , et al.   Environmental microarray analyses of Antarctic soil microbial communities . ISME J . 2009;3:340–351
  31. Sunagawa S , DeSantis TZ , Piceno YM , et al.   Bacterial diversity and White Plague Disease-associated community changes in the Caribbean coral Montastraea faveolata . ISME J . 2009;3:512–521
  32. Brodie EL , DeSantis TZ , Parker JP , et al.   Urban aerosols harbor diverse and dynamic bacterial populations . Proc Natl Acad Sci USA . 2007;104:299–304
  33. Hugenholtz P . Exploring prokaryotic diversity in the genomic era . Genome Biol . 2002;3: REVIEWS0003
  34. Czyzewski DI , Lane MM , Weidler EM , et al.   The interpretation of Rome III criteria and method of assessment affect the irritable bowel syndrome classification of children . Aliment Pharmacol Ther . 2010;33:403–411
  35. Rautio M , Eerola E , Vaisanen-Tunkelrott ML , et al.   Reclassification of Bacteroides putredinis (Weinberg et al, 1937) in a new genus Alistipes gen. nov., as Alistipes putredinis comb. nov., and description of Alistipes finegoldii sp nov., from human sources . Syst Appl Microbiol . 2003;26:182–188
  36. Rautio M , Lonnroth M , Saxen H , et al.   Characteristics of an unusual anaerobic pigmented gram-negative rod isolated from normal and inflamed appendices . Clin Infect Dis . 1997;25(Suppl 2):S107–S110
  37. Rigottier-Gois L , Rochet V , Garrec N , et al.   Enumeration of Bacteroides species in human faeces by fluorescent in situ hybridisation combined with flow cytometry using 16S rRNA probes . Syst Appl Microbiol . 2003;26:110–118
  38. Rautio M , Saxen H , Siitonen A , et al.   Bacteriology of histopathologically defined appendicitis in children . Pediatr Infect Dis J . 2000;19:1078–1083
  39. Krogius-Kurikka L , Lyra A , Malinen E , et al.   Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers . BMC Gastroenterol . 2009;9:95
  40. Justesen T , Nielsen OH , Hjelt K , et al.   Normal cultivable microflora in upper jejunal fluid in children without gastrointestinal disorders . J Pediatr Gastroenterol Nutr . 1984;3:683–686
  41. Tana C , Umesaki Y , Imaoka A , et al.   Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome . Neurogastroenterol Motil . 2010;22:512–519 e114–e115
  42. Yang L , Lu X , Nossa CW , et al.   Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome . Gastroenterology . 2009;137:588–597
  43. Malinen E , Krogius-Kurikka L , Lyra A , et al.   Association of symptoms with gastrointestinal microbiota in irritable bowel syndrome . World J Gastroenterol . 2010;16:4532–4540
  44. Nomura T , Ohkusa T , Okayasu I , et al.   Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy . Aliment Pharmacol Ther . 2005;21:1017–1027
  45. Rajilić-Stojanović M . Diversity of the human gastrointestinal microbiota novel perspectives from high troughput analyses . Wageningen, The Netherlands: Wageningen University; 2007;
  46. Pimentel M . Evaluating a bacterial hypothesis in IBS using a modification of Koch's postulates: part 1 . Am J Gastroenterol . 2010;105:718–721
  47. Spiegel BM . Questioning the bacterial overgrowth hypothesis of irritable bowel syndrome: an epidemiologic and evolutionary perspective . Clin Gastroenterol Hepatol . 2011;9:461–469
  48. Posserud I , Stotzer PO , Bjornsson ES , et al.   Small intestinal bacterial overgrowth in patients with irritable bowel syndrome . Gut . 2007;56:802–808
  49. Yu D , Cheeseman F , Vanner S . Combined oro-caecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects oro-caecal transit, not small intestinal bacterial overgrowth in patients with IBS . Gut . 2011;60:334–340
  50. Shulman RJ , Eakin MN , Czyzewski DI , et al.   Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome . J Pediatr . 2008;153:646–650
  51. Pimentel M , Lembo A , Chey WD , et al.   Rifaximin therapy for patients with irritable bowel syndrome without constipation . N Engl J Med . 2011;364:22–32
  52. Hoveyda N , Heneghan C , Mahtani KR , et al.   A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome . BMC Gastroenterol . 2009;9:15
  53. De Filippo C , Cavalieri D , Di Paola M , et al.   Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa . Proc Natl Acad Sci U S A . 2010;107:14691–14696
  54. Ciccarelli FD , Doerks T , von Mering C , et al.   Toward automatic reconstruction of a highly resolved tree of life . Science . 2006;311:1283–1287

 Conflicts of interest The authors disclose the following: Versalovic serves on an advisory board for Danone and he receives unrestricted research support from Biogaia AB. The remaining authors disclose no conflicts.

 Funding Supported by the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) and the National Center for Complementary and Alternative Medicine (NCCAM) from the National Institute of Health (NIH) (grant UH2 DK083990-01 and UH3 DK083990-02). The work in J.V.'s laboratory is supported by NIDDK (R01 DK065075 and P30 DK56338), NIH National Center for Complementary and Alternative Medicine (R01 AT004326 and R21 AT003102), and NHGRI (HMP sampling Jumpstart 5U54 HG003273-08, with R.G. as principal investigator). S.V.L. is supported by the Rainin Foundation.

PII: S0016-5085(11)00922-X

doi: 10.1053/j.gastro.2011.06.072

Gastroenterology
Volume 141, Issue 5 , Pages 1782-1791 , November 2011

Article Tools

* Image Usage & Resolution