A 10-Year Follow-up Study of the Natural History of Perianal Crohn's Disease in a Danish Population-Based Inception Cohort.

BACKGROUND: Perianal complications in patients with Crohn's disease are common and have a negative impact on the patients' quality of life. Data about the long-term disease course of perianal Crohn's disease in the era of biological treatment are limited. In this population-based cohort study, we sought to investigate the occurrence, clinical risk factors, and disease course of perianal disease. METHODS: A total of 213 Crohn's disease patients were included in a prospective population-based inception cohort. Data were retrieved from medical records and national health administrative databases. Perianal disease was defined as a perianal fistula and/or abscess. Associations between outcomes and covariates were analyzed by Cox regression analysis. RESULTS: A total of 48 (22.5%) patients developed perianal disease after 10 years. Colonic disease location (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.01-3.92) and penetrating behavior (HR, 5.65; 95% CI, 2.65-12.03) were associated with the development of perianal disease. The cumulative risk of undergoing abdominal surgery was 51% after 10 years. Patients with perianal disease had a higher rate of resection (HR, 3.92; 95% CI, 1.86-8.67) and hospitalization (HR, 1.01; 95% CI, 1.00-1.01). There was no significant difference in the rate of sick leave, unemployment, or disability pension between patients with and without perianal disease. CONCLUSIONS: Patients with perianal disease carry a higher risk of surgery and hospitalization, and this suggests a more severe disease course and poorer prognosis among these patients, even in the era of biological treatment. These findings underline the importance of optimizing treatment strategies for patients with perianal disease.

Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study.

OBJECTIVE: IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS. DESIGN: We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected. RESULTS: A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not. CONCLUSION: In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS. TRIAL REGISTRATION NUMBER: NCT02788071.

Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies.

Inflammatory bowel disease (IBD) is a chronic intestinal disorder, with two main types: Crohn's disease (CD) and ulcerative colitis (UC), whose molecular pathology is not well understood. The majority of IBD-associated SNPs are located in non-coding regions and are hard to characterize since regulatory regions in IBD are not known. Here we profile transcription start sites (TSSs) and enhancers in the descending colon of 94 IBD patients and controls. IBD-upregulated promoters and enhancers are highly enriched for IBD-associated SNPs and are bound by the same transcription factors. IBD-specific TSSs are associated to genes with roles in both inflammatory cascades and gut epithelia while TSSs distinguishing UC and CD are associated to gut epithelia functions. We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.