Host Genetics and Environmental Factors Regulate Ecological Succession of the Mouse Colon Tissue-Associated Microbiota

Background: The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier. Methodology/Principal Findings: Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice. Results: In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota

Preventing postoperative recurrence of Crohn's disease.

BACKGROUND AND METHODS: Risk factors for recurrence of Crohn's disease and the evidence for progress in reducing recurrence following resection were reviewed. A Medline based literature review was carried out. RESULTS AND CONCLUSION: Only smoking has been confirmed as a significant adverse risk factor for recurrence. Evidence for differing recurrence rates in fibrostenosing disease and perforating disease is inconclusive, but such a classification along with the endoscopic findings of recurrence may have a place in the analysis of therapeutic trials. Minimal resectional surgery with clearing of only macroscopic disease seems to be justified, with no clear benefits from different anastomotic techniques. Recent trials offer encouraging evidence of the usefulness of 5-aminosalicylic acid, particularly higher-dose regimens started early after resection, although the long-term benefits are uncertain. The oral steroid, budesonide, offers a potent treatment with minimal side-effects, but evidence of its prevention of recurrence is presently weak

Connective tissue changes in ileal Crohn's disease: relationship to disease phenotype and ulcer-associated cell lineage.

PURPOSE: Abnormalities of enteric collagen and smooth-muscle cell content have been documented in Crohn's disease. We studied the relationships among connective tissue changes, disease "type," and other disease features using immunohistochemistry and image analysis. METHODS: Twenty consecutive ileal resections for Crohn's disease and ten normal terminal ileal specimens were evaluated using conventional histopathologic examination. Monoclonal antibodies to smooth-muscle actin and Type III collagen fibers were used to determine the percentage area of the submucosa occupied by these constituents using image analysis. RESULTS: There were no significant differences in smooth-muscle content among stenosed, perforated, and ulcerated specimens. There was a significantly increased submucosal Type III collagen content in stenosed vs. other types. The only factor that correlated with smooth-muscle cell content was the amount of ulcer-associated cell lineage present. CONCLUSIONS: Increased deposition of Type III collagen fibers rather than smooth-muscle proliferation is associated with a stenotic phenotype. Loss of Type III collagen fibers may play a role in the development of perforating complications. We have found no evidence that smooth-muscle cells are the source of Type III collagen fiber production although there is evidence that ulcer-associated cell lineage may be related to the stimulus leading to submucosal neomuscularization