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Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA

BACKGROUND: A critical role for the gut epithelium lies in its ability to discriminate between pathogens and commensals and respond appropriately. Dysfunctional interactions between microbes and epithelia are believed to have a role in inflammatory bowel disease (IBD). In this study, we analyzed mic...

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Autores principales: Hotte, Naomi S. C., Salim, Saad Y., Tso, Robert H., Albert, Eric J., Bach, Phil, Walker, John, Dieleman, Levinus A., Fedorak, Richard N., Madsen, Karen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359330/
https://www.ncbi.nlm.nih.gov/pubmed/22649567
http://dx.doi.org/10.1371/journal.pone.0037932
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author Hotte, Naomi S. C.
Salim, Saad Y.
Tso, Robert H.
Albert, Eric J.
Bach, Phil
Walker, John
Dieleman, Levinus A.
Fedorak, Richard N.
Madsen, Karen L.
author_facet Hotte, Naomi S. C.
Salim, Saad Y.
Tso, Robert H.
Albert, Eric J.
Bach, Phil
Walker, John
Dieleman, Levinus A.
Fedorak, Richard N.
Madsen, Karen L.
author_sort Hotte, Naomi S. C.
collection PubMed
description BACKGROUND: A critical role for the gut epithelium lies in its ability to discriminate between pathogens and commensals and respond appropriately. Dysfunctional interactions between microbes and epithelia are believed to have a role in inflammatory bowel disease (IBD). In this study, we analyzed microbiota and gene expression in IBD patients and examined responses of mucosal biopsies to bacterial DNA. METHODS: Biopsies were taken from non-inflamed areas of the colon in healthy controls (HC) and Crohn's disease (CD) and ulcerative colitis (UC) patients in remission. Biopsies were snap-frozen or cultured with DNA from Lactobacillus plantarum (LP) or Salmonella dublin (SD). Gene expression was analyzed under basal conditions and in response to DNA. Gene networks were analyzed using Ingenuity Pathways software. Mucosal-associated microbiota was analyzed using terminal restriction fragment length polymorphism. Frequency of single nucleotide polymorphisms in NOD2 and TLR9 was assessed. RESULTS: Patients with IBD had altered microbiota, enhanced expression of inflammatory genes, and increased correlations between specific gene expression and microbes. Principle component analysis showed CD and UC patients to cluster independently from healthy controls in both gene expression and microbial analysis. DNA from LP stimulated anti-inflammatory pathways in controls and UC patients, but induced an upregulation of IL17A in CD patients. There were no differences in SNP frequencies of TLR9 or NOD2 in the groups. CONCLUSIONS: Patients with Crohn's disease exhibit altered responses to bacterial DNA. These findings suggest that the gut response to bacterial DNA may depend not only on the specific type of bacterial DNA, but also on the host.
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spelling pubmed-33593302012-05-30 Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA Hotte, Naomi S. C. Salim, Saad Y. Tso, Robert H. Albert, Eric J. Bach, Phil Walker, John Dieleman, Levinus A. Fedorak, Richard N. Madsen, Karen L. PLoS One Research Article BACKGROUND: A critical role for the gut epithelium lies in its ability to discriminate between pathogens and commensals and respond appropriately. Dysfunctional interactions between microbes and epithelia are believed to have a role in inflammatory bowel disease (IBD). In this study, we analyzed microbiota and gene expression in IBD patients and examined responses of mucosal biopsies to bacterial DNA. METHODS: Biopsies were taken from non-inflamed areas of the colon in healthy controls (HC) and Crohn's disease (CD) and ulcerative colitis (UC) patients in remission. Biopsies were snap-frozen or cultured with DNA from Lactobacillus plantarum (LP) or Salmonella dublin (SD). Gene expression was analyzed under basal conditions and in response to DNA. Gene networks were analyzed using Ingenuity Pathways software. Mucosal-associated microbiota was analyzed using terminal restriction fragment length polymorphism. Frequency of single nucleotide polymorphisms in NOD2 and TLR9 was assessed. RESULTS: Patients with IBD had altered microbiota, enhanced expression of inflammatory genes, and increased correlations between specific gene expression and microbes. Principle component analysis showed CD and UC patients to cluster independently from healthy controls in both gene expression and microbial analysis. DNA from LP stimulated anti-inflammatory pathways in controls and UC patients, but induced an upregulation of IL17A in CD patients. There were no differences in SNP frequencies of TLR9 or NOD2 in the groups. CONCLUSIONS: Patients with Crohn's disease exhibit altered responses to bacterial DNA. These findings suggest that the gut response to bacterial DNA may depend not only on the specific type of bacterial DNA, but also on the host. Public Library of Science 2012-05-23 /pmc/articles/PMC3359330/ /pubmed/22649567 http://dx.doi.org/10.1371/journal.pone.0037932 Text en Hotte et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hotte, Naomi S. C.
Salim, Saad Y.
Tso, Robert H.
Albert, Eric J.
Bach, Phil
Walker, John
Dieleman, Levinus A.
Fedorak, Richard N.
Madsen, Karen L.
Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA
title Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA
title_full Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA
title_fullStr Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA
title_full_unstemmed Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA
title_short Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNA
title_sort patients with inflammatory bowel disease exhibit dysregulated responses to microbial dna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359330/
https://www.ncbi.nlm.nih.gov/pubmed/22649567
http://dx.doi.org/10.1371/journal.pone.0037932
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