title: The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study.
abstract: BACKGROUND
  Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.
  
  
  METHODS
  100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.
  
  
  RESULTS
  129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).
  
  
  CONCLUSIONS
  This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.
  
  
  BACKGROUND
  This study is publically registered on the United Kingdom Clinical Research Network Portfolio (9633).
authors.affiliation: Gastrointestinal Research Group, Division of Applied Medicine, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Hansen
authors.forename: Susan H
authors.initials: SH
authors.lastname: Berry
authors.forename: Indrani
authors.initials: I
authors.lastname: Mukhopadhya
authors.forename: John M
authors.initials: JM
authors.lastname: Thomson
authors.forename: Karin A
authors.initials: KA
authors.lastname: Saunders
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Nicholl
authors.forename: W Michael
authors.initials: WM
authors.lastname: Bisset
authors.forename: Sabarinathan
authors.initials: S
authors.lastname: Loganathan
authors.forename: Gamal
authors.initials: G
authors.lastname: Mahdi
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kastner-Cole
authors.forename: Andy R
authors.initials: AR
authors.lastname: Barclay
authors.forename: Jon
authors.initials: J
authors.lastname: Bishop
authors.forename: Diana M
authors.initials: DM
authors.lastname: Flynn
authors.forename: Paraic
authors.initials: P
authors.lastname: McGrogan
authors.forename: Richard K
authors.initials: RK
authors.lastname: Russell
authors.forename: Emad M
authors.initials: EM
authors.lastname: El-Omar
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Hold
mesh_terms: D000293:Adolescent; D002167:Campylobacter / Q000145:classification / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000382:microbiology*; D008297:Male; D054892:Metagenome / Q000235:genetics; D012336:RNA, Ribosomal, 16S
chemical_list: D012336:RNA, Ribosomal, 16S
references.citation: Inflamm Bowel Dis. 2012 Jun;18(6):999-1005
references.pmid: 21688352
references.citation: Nature. 2012 Jun 13;486(7402):207-14
references.pmid: 22699609
references.citation: Int J Syst Bacteriol. 1996 Jan;46(1):252-8
references.pmid: 8573504
references.citation: PLoS One. 2011;6(6):e21490
references.pmid: 21738679
references.citation: Am J Gastroenterol. 2010 Dec;105(12):2687-92
references.pmid: 20940708
references.citation: FEMS Microbiol Ecol. 2002 Jan 1;39(1):33-9
references.pmid: 19709182
references.citation: PLoS One. 2011;6(9):e25417
references.pmid: 21966525
references.citation: Inflamm Bowel Dis. 2013 Jan;19(1):73-80
references.pmid: 22535573
references.citation: Inflamm Bowel Dis. 2011 Jan;17(1):423-39
references.pmid: 20564651
references.citation: J Clin Microbiol. 2004 Jun;42(6):2766-8
references.pmid: 15184464
references.citation: Science. 2005 Jun 10;308(5728):1635-8
references.pmid: 15831718
references.citation: Nature. 2012 Nov 1;491(7422):119-24
references.pmid: 23128233
references.citation: Gastroenterology. 2008 Oct;135(4):1114-22
references.pmid: 18725221
references.citation: Nature. 2011 Sep 21;478(7368):250-4
references.pmid: 21937990
references.citation: Nat Rev Gastroenterol Hepatol. 2012 Feb 21;9(4):219-30
references.pmid: 22349170
references.citation: Nat Genet. 2009 Dec;41(12):1335-40
references.pmid: 19915574
references.citation: J Clin Microbiol. 2006 Jun;44(6):2276-9
references.pmid: 16757639
references.citation: J Clin Microbiol. 2009 Feb;47(2):453-5
references.pmid: 19052183
references.citation: Am J Gastroenterol. 2012 Dec;107(12):1913-22
references.pmid: 23044767
references.citation: Inflamm Bowel Dis. 2010 Jun;16(6):1008-16
references.pmid: 19885905
references.citation: Nature. 2010 Mar 4;464(7285):59-65
references.pmid: 20203603
references.citation: Nat Rev Microbiol. 2012 Nov;10(11):735-42
references.pmid: 23000955
references.citation: J Gastroenterol. 2010 Mar;45(3):266-76
references.pmid: 20076977
references.citation: J Clin Microbiol. 2004 Feb;42(2):874-6
references.pmid: 14766877
references.citation: mBio. 2012 Feb 14;3(1):
references.pmid: 22334515
references.citation: Clin Exp Immunol. 2011 Feb;163(2):250-9
references.pmid: 21087444
references.citation: Gastroenterology. 1998 Apr;114(4):755-63
references.pmid: 9516396
references.citation: Gut. 2007 Dec;56(12):1696-705
references.pmid: 17682002
references.citation: Gut. 2004 Jan;53(1):1-4
references.pmid: 14684564
references.citation: Inflamm Bowel Dis. 2011 Jun;17(6):1314-21
references.pmid: 21560194
references.citation: Res Microbiol. 1996 Nov-Dec;147(9):707-18
references.pmid: 9296105
references.citation: Scand J Gastroenterol Suppl. 1989;170:2-6; discussion 16-9
references.pmid: 2617184
references.citation: J Clin Microbiol. 2000 Jul;38(7):2798-9
references.pmid: 10979752
references.citation: Can J Gastroenterol. 2005 Sep;19 Suppl A:5A-36A
references.pmid: 16151544
references.citation: Helicobacter. 2008 Aug;13(4):234-8
references.pmid: 18665930
references.citation: Gut. 1994 Oct;35(10):1385-8
references.pmid: 7959192
references.citation: Appl Environ Microbiol. 2002 Oct;68(10):5164-6
references.pmid: 12324369
references.citation: PLoS One. 2011 Feb 23;6(2):e17184
references.pmid: 21383845
references.citation: Aliment Pharmacol Ther. 2009 Aug;30(3):283-93
references.pmid: 19438427
references.citation: FEMS Immunol Med Microbiol. 2011 Feb;61(1):1-14
references.pmid: 20955468
references.citation: J Infect Dis. 2010 Dec 15;202(12):1855-65
references.pmid: 21050118
references.citation: PLoS One. 2011;6(10):e27076
references.pmid: 22073125
references.citation: J Pediatr Gastroenterol Nutr. 2005 Jul;41(1):1-7
references.pmid: 15990620
references.citation: Arch Dis Child. 2012 Jul;97(7):590-4
references.pmid: 22550323
references.citation: Pediatrics. 2012 Oct;130(4):e794-803
references.pmid: 23008454
references.citation: Helicobacter. 2010 Dec;15(6):549-57
references.pmid: 21073612
references.citation: Nat Rev Immunol. 2009 May;9(5):313-23
references.pmid: 19343057
references.citation: Aliment Pharmacol Ther. 2003 Sep 1;18(5):481-6
references.pmid: 12950420
references.citation: Colorectal Dis. 2010 Jan;12(1):48-53
references.pmid: 20050183
references.citation: mBio. 2012 Jan 10;3(1):
references.pmid: 22233678