Abstract
The aim of this study was to integrate human clinical, genotype, mRNA microarray and 16 S rRNA sequence data collected on 84 subjects with ileal Crohn’s disease, ulcerative colitis or control patients without inflammatory bowel diseases in order to interrogate how host-microbial interactions are perturbed in inflammatory bowel diseases (IBD). Ex-vivo ileal mucosal biopsies were collected from the disease unaffected proximal margin of the ileum resected from patients who were undergoing initial intestinal surgery. Both RNA and DNA were extracted from the mucosal biopsy samples. Patients were genotyped for the three major NOD2 variants (Leufs1007, R702W, and G908R) and the ATG16L1T300A variant. Whole human genome mRNA expression profiles were generated using Agilent microarrays. Microbial composition profiles were determined by 454 pyrosequencing of the V3–V5 hypervariable region of the bacterial 16 S rRNA gene. The results of permutation based multivariate analysis of variance and covariance (MANCOVA) support the hypothesis that host mucosal Paneth cell and xenobiotic metabolism genes play an important role in host microbial interactions.
Highlights
Inflammatory bowel diseases are complex genetic disorders resulting from the interplay of genetic and environmental factors [1,2,3]
Because there is evidence that isolated Crohn’s colitis are associated with genetic factors that are distinct from ileal Crohn’s diseases (CD), and the overlap between genetic factors associated with ulcerative colitis (UC) and isolated Crohn’s colitis, we have focused our attention on the ileal CD subphenotype as a relatively homogenous category that is distinct from isolated colitis (CD or UC) and non-inflammatory bowel diseases (IBD) controls [4,5,6]
We previously reported that increased CD3D mRNA expression in disease affected ileum resected from 18 ileal CD patients was associated with NOD2 genotype [15]
Summary
Inflammatory bowel diseases are complex genetic disorders resulting from the interplay of genetic and environmental factors [1,2,3]. Crohn’s diseases (CD) and ulcerative colitis (UC) represent the two major inflammatory bowel diseases (IBD) phenotypes and are distinguished by different patterns of disease location. The inflammation in CD patients may be located anywhere along the gastrointestinal tract, but in the majority (80%) of CD patients, the terminal ileum is involved. We previously reported that increased CD3D mRNA expression in disease affected ileum resected from 18 ileal CD patients was associated with NOD2 genotype [15]. We observed alterations in mRNA gene expression in the disease unaffected proximal margin of resected ileum from 19 ileal CD patients compared to 9 control non-IBD patients, regardless of NOD2 genotype [15].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
