No abstract

Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.

No abstract

Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease (IBD), are chronic, spontaneously relapsing disorders of unknown cause. These diseases appear to be immunologically mediated and have genetic and environmental influences. Although the cause of these diseases remains obscure, the pathogenesis of chronic intestinal inflammation is becoming clearer, due to improved animal models of enterocolitis and important advances in immunological techniques. Traditional therapy for IBD, although helping to induce and maintain disease remission, does little to alter the underlying fundamental disease process. New IBD therapy has not developed significantly over the past twenty years and includes 5-aminosalicylic acid preparations, corticosteroids and immunomodulatory agents, such as azathioprine, 6-mercaptopurine and methotrexate. There is, therefore, a need for new, specific disease-modifying therapy and the development of such therapy has been hastened by a greater understanding of the pathophysiology of IBD. This review examines the most recent novel therapies for IBD, with specific emphasis on immunomodulatory and novel anti-inflammatory therapies. Recent clinical trials are reviewed, and the potential advances and clinical impact that these novel agents may provide are discussed.