Abstract
BackgroundCeliac 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.MethodsWe 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.ResultsThe 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 co5mpared to HC.ConclusionsThe 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.
Highlights
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
Composition of the duodenal mucosal microbiota Human intestinal tract chip (HITChip) microbiota profiles were obtained from 10 CD subjects (4 males and 6 females) and 9 healthy controls (HC, median age 9 ± 4.1 years, 4 males and 5 females)
There were no significant differences in the abundance of bacterial phylum-like groups between CD and HC
Summary
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. A balanced commensal microbiota contributes to the physiological development of the gut and the maturation of the immune system; thereby, alterations in the intestinal microbiota could play a role in the onset of different diseases, including CD [3,11]. Two recent studies have addressed the microbiota in infants with a genetic predisposition to CD [4,11] Both of these reported the microbiota of predisposed infants to be different from that of non-predisposed, but while Sellitto et al reported a reduction or lack of Bacteroides in predisposed infants [4], De Palma et al found that Bacteroides fragilis and staphylococci were increased and bifidobacteria were reduced in genetically susceptible infants [11]. The idea that the microbiota is involved in the etiology of CD has been addressed in numerous studies, the results on specific CD-associated microbiota changes remain inconclusive
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