Patients with Inflammatory Bowel Disease Exhibit Dysregulated Responses to Microbial DNAReport as inadecuate




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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.



Author: Naomi S. C. Hotte, Saad Y. Salim, Robert H. Tso, Eric J. Albert, Phil Bach, John Walker, Levinus A. Dieleman, Richard N. Fedorak,

Source: http://plos.srce.hr/



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