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Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease.

Cheng J, Kalliomäki M, Heilig HG, Palva A, Lähteenoja H, de Vos WM, Salojärvi J, Satokari R - BMC Gastroenterol (2013)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Biosciences, University of Helsinki, P.O. Box 66, Helsinki FI-00014, Finland.

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.

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Related in: MedlinePlus

Sub-profile of the duodenal microbiota separating celiac disease (CD) and healthy control (HC) children. A) Eight HITChip genus-like level bacterial groups selected with random forest and cross-validation showing higher abundance in either HC (5 groups) or CD (3 groups). The error rate of random forest is 31.6%, whereas 95% confidence intervals for random assignment are [32%, 74%]. B) The profile of eight bacterial groups separates healthy control children (HC) and celiac disease children (CD) in redundancy analysis (RDA). p-value obtained by permutation test (50000 permutations) is 0.050.
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Figure 4: Sub-profile of the duodenal microbiota separating celiac disease (CD) and healthy control (HC) children. A) Eight HITChip genus-like level bacterial groups selected with random forest and cross-validation showing higher abundance in either HC (5 groups) or CD (3 groups). The error rate of random forest is 31.6%, whereas 95% confidence intervals for random assignment are [32%, 74%]. B) The profile of eight bacterial groups separates healthy control children (HC) and celiac disease children (CD) in redundancy analysis (RDA). p-value obtained by permutation test (50000 permutations) is 0.050.

Mentions: Further analysis was performed with random forests using feature selection as preprocessing step, where the best method was chosen from six candidates using cross-validation. The aim was to identify a possible health status-related bacterial sub-population within the total microbiota. The feature selection method resulting in lowest cross-validated prediction error was to choose a set of eight genus-like bacteria having lowest p-values from t-test (Figure 4). Thus, although no single genus-like group individually differed significantly between HC and CD, a random forest learned with a profile of selected eight genus-like groups predicted the health status with error rate of 31.6%. This is significantly better than random guess, having a median error rate of 53%, and 95% confidence intervals of [32%, 74%].


Duodenal microbiota composition and mucosal homeostasis in pediatric celiac disease.

Cheng J, Kalliomäki M, Heilig HG, Palva A, Lähteenoja H, de Vos WM, Salojärvi J, Satokari R - BMC Gastroenterol (2013)

Sub-profile of the duodenal microbiota separating celiac disease (CD) and healthy control (HC) children. A) Eight HITChip genus-like level bacterial groups selected with random forest and cross-validation showing higher abundance in either HC (5 groups) or CD (3 groups). The error rate of random forest is 31.6%, whereas 95% confidence intervals for random assignment are [32%, 74%]. B) The profile of eight bacterial groups separates healthy control children (HC) and celiac disease children (CD) in redundancy analysis (RDA). p-value obtained by permutation test (50000 permutations) is 0.050.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3716955&req=5

Figure 4: Sub-profile of the duodenal microbiota separating celiac disease (CD) and healthy control (HC) children. A) Eight HITChip genus-like level bacterial groups selected with random forest and cross-validation showing higher abundance in either HC (5 groups) or CD (3 groups). The error rate of random forest is 31.6%, whereas 95% confidence intervals for random assignment are [32%, 74%]. B) The profile of eight bacterial groups separates healthy control children (HC) and celiac disease children (CD) in redundancy analysis (RDA). p-value obtained by permutation test (50000 permutations) is 0.050.
Mentions: Further analysis was performed with random forests using feature selection as preprocessing step, where the best method was chosen from six candidates using cross-validation. The aim was to identify a possible health status-related bacterial sub-population within the total microbiota. The feature selection method resulting in lowest cross-validated prediction error was to choose a set of eight genus-like bacteria having lowest p-values from t-test (Figure 4). Thus, although no single genus-like group individually differed significantly between HC and CD, a random forest learned with a profile of selected eight genus-like groups predicted the health status with error rate of 31.6%. This is significantly better than random guess, having a median error rate of 53%, and 95% confidence intervals of [32%, 74%].

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Veterinary Biosciences, University of Helsinki, P.O. Box 66, Helsinki FI-00014, Finland.

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.

Show MeSH
Related in: MedlinePlus