Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease

BMC Gastroenterol. 2013 Jul 11:13:113. doi: 10.1186/1471-230X-13-113.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Celiac Disease / genetics
  • Celiac Disease / metabolism*
  • Celiac Disease / microbiology*
  • Chemokine CXCL16
  • Chemokines, CXC / genetics
  • Child
  • Child, Preschool
  • Connexin 43 / genetics
  • Duodenum / metabolism*
  • Duodenum / microbiology*
  • Female
  • Gene Expression
  • Homeostasis
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology*
  • Male
  • Metagenome
  • Middle Aged
  • Mucin-2 / genetics
  • Pancreatitis-Associated Proteins
  • Proteins / genetics
  • Receptors, CXCR6
  • Receptors, Chemokine / genetics
  • Receptors, Scavenger / genetics
  • Receptors, Virus / genetics
  • Signal Transduction
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 9 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Zonula Occludens-1 Protein / genetics

Substances

  • CXCL16 protein, human
  • CXCR6 protein, human
  • Chemokine CXCL16
  • Chemokines, CXC
  • Connexin 43
  • MUC2 protein, human
  • Mucin-2
  • Pancreatitis-Associated Proteins
  • Proteins
  • REG3G protein, human
  • Receptors, CXCR6
  • Receptors, Chemokine
  • Receptors, Scavenger
  • Receptors, Virus
  • TLR2 protein, human
  • TLR9 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha
  • Zonula Occludens-1 Protein
  • Interleukin-10
  • Interferon-gamma