title: Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease.
abstract: BACKGROUND
  Celiac disease (CD) is an autoimmune disorder of the small intestine which is triggered by dietary gluten in genetically predisposed (HLA-DQ2/DQ8 positive) individuals. Only a fraction of HLA-DQ2/DQ8 positive individuals develop CD indicating that other factors have a role in the disorder. Several studies have addressed intestinal microbiota aberrancies in pediatric CD, but the results are inconsistent. Previously, we demonstrated that pediatric CD patients have lower duodenal expression of TLR2 and higher expression of TLR9 as compared to healthy controls (HC) indicating that microbiota may have a role in CD.
  
  
  METHODS
  We used bacterial phylogenetic microarray to comprehensively profile the microbiota in duodenal biopsies of CD (n = 10) and HC (n = 9) children. The expression of selected mucosa-associated genes was assessed by qRT-PCR in CD and HC children and in treated CD adults (T-CD, n = 6) on gluten free diet.
  
  
  RESULTS
  The overall composition, diversity and the estimated microbe associated molecular pattern (MAMP) content of microbiota were comparable between CD and HC, but a sub-population profile comprising eight genus-like bacterial groups was found to differ significantly between HC and CD. In HC, increased TLR2 expression was positively correlated with the expression of tight junction protein ZO-1. In CD and T-CD, the expression of IL-10, IFN-g and CXCR6 were higher as compared to HC.
  
  
  CONCLUSIONS
  The results suggest that microbiota and altered expression of mucosal receptors have a role in CD. In CD subjects, the increased expression of IL-10 and IFN-g may have partly resulted from the increased TLR9 expression and signaling.
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, P.O. Box 66, Helsinki FI-00014, Finland.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Marko
authors.initials: M
authors.lastname: Kalliomäki
authors.forename: Hans G H J
authors.initials: HG
authors.lastname: Heilig
authors.forename: Airi
authors.initials: A
authors.lastname: Palva
authors.forename: Hannu
authors.initials: H
authors.lastname: Lähteenoja
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.forename: Jarkko
authors.initials: J
authors.lastname: Salojärvi
authors.forename: Reetta
authors.initials: R
authors.lastname: Satokari
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018031:Connexin 43 / Q000235:genetics; D004386:Duodenum / Q000378:metabolism* / Q000382:microbiology*; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D008875:Middle Aged; D055262:Mucin-2 / Q000235:genetics; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins / Q000235:genetics; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics; D051116:Receptors, Scavenger / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D062826:Zonula Occludens-1 Protein / Q000235:genetics
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D018031:Connexin 43; C524625:MUC2 protein, human; D055262:Mucin-2; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C494437:REG3G protein, human; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus; C495342:TLR2 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D016753:Interleukin-10; D007371:Interferon-gamma