ILC3 function as a double-edged sword in inflammatory bowel diseases

Inflammatory bowel diseases (IBD), composed mainly of Crohn’s disease (CD) and ulcerative colitis (UC), are strongly implicated in the development of intestinal inflammation lesions. Its exact etiology and pathogenesis are still undetermined. Recently accumulating evidence supports that group 3 innate lymphoid cells (ILC3) are responsible for gastrointestinal mucosal homeostasis through moderate generation of IL-22, IL-17, and GM-CSF in the physiological state. ILC3 contribute to the progression and aggravation of IBD while both IL-22 and IL-17, along with IFN-γ, are overexpressed by the dysregulation of NCR− ILC3 or NCR+ ILC3 function and the bias of NCR+ ILC3 towards ILC1 as well as regulatory ILC dysfunction in the pathological state. Herein, we feature the group 3 innate lymphoid cells’ development, biological function, maintenance of gut homeostasis, mediation of IBD occurrence, and potential application to IBD therapy

Systematic meta-analyses and field synopsis of genetic and epigenetic studies in paediatric inflammatory bowel disease

We provide a comprehensive field synopsis of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD). A systematic review was performed and included 84 genetic association studies reporting data for 183 polymorphisms in 71 genes. Meta-analyses were conducted for 20 SNPs in 10 genes of paediatric Crohn’s disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC). Five epigenetic studies were also included, but formal meta-analysis was not possible. Venice criteria and Bayesian false discovery probability test were applied to assess the credibility of associations. Nine SNPs in 4 genes were considered to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs12521868, rs26313667, rs1800629) were not previously identified in paediatric GWAS. Differential DNA methylation in NOD2 and TNF-α, dysregulated expression in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated. Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, with similar magnitudes of associations. Early onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic changes, but these findings need to be replicated. Further progress identifying genetic and epigenetic susceptibility of paediatric IBD will require international collaboration, population diversity and harmonization of protocols

MicroRNAs: new players in IBD

MicroRNAs (miRNAs) are small non-coding RNAs, 18–23 nucleotides long, which act as post-transcriptional regulators of gene expression. miRNAs are strongly implicated in the pathogenesis of many common diseases, including IBDs. This review aims to outline the history, biogenesis and regulation of miRNAs. The role of miRNAs in the development and regulation of the innate and adaptive immune system is discussed, with a particular focus on mechanisms pertinent to IBD and the potential translational applications

Comparison of mortality following hospitalisation for ulcerative colitis in Scotland between 1998–2000 and 2007–2009

Background Scottish nationwide linkage data from 1998 to 2000 demonstrated high 3‐year mortality in patients hospitalised with ulcerative colitis (UC). Aim To compare 3‐year mortality, and factors related to mortality, in Scottish patients hospitalised with UC between 1998–2000 and 2007–2009. Methods The Scottish Morbidity Records and linked datasets were used to assess 3‐year mortality, standardised mortality ratio (SMR) and multivariate analyses of factors associated with 3‐year mortality. The 3‐year mortality was determined after four admission types: surgery‐elective or emergency; medical‐elective or emergency. Age‐standardised mortality rates (ASR) were used to compare mortality rates between periods. Results Ulcerative colitis admissions increased from 10.6 in Period 1 to 11.6 per 100 000 population per year in Period 2 (P = 0.046). Crude and adjusted 3‐year mortality fell between time periods (crude 12.2% to 8.3%; adjusted OR 0.59, CI 0.42–0.81, P = 0.04). Adjusted 3‐year mortality following emergency medical admission (OR 0.58, CI 0.39–0.87, P = 0.003) and in patients >65 years (38.8% to 28.7%, P = 0.02) was lower in Period 2. The SMR in period 1 was 3.04 and 2.96 in Period 2. Directly age‐standardised mortality decreased from 373 (CI 309–437) to 264 (CI 212–316) per 10 000 person‐years. On multivariate analysis, increasing age (50–64 years OR 7.11 (CI 2.77–18.27, P < 0.05); 65–74 years OR 14.70 (CI 5.65–38.25 P < 0.05); >75 years OR 46.42 (CI 18.29–117.78, P < 0.001) and co‐morbidity (OR 3.02, CI 1.72–5.28, P < 0.001) were significantly associated with 3‐year mortality in Period 2. Conclusions Comparisons of crude and adjusted mortality rates suggest significant improvement in outcome over the last decade – however, mortality remains high, and older age and co‐morbidity are important predictors of outcome

Comparison of mortality following hospitalisation for ulcerative colitis in Scotland between 1998–2000 and 2007–2009

Background Scottish nationwide linkage data from 1998 to 2000 demonstrated high 3‐year mortality in patients hospitalised with ulcerative colitis (UC). Aim To compare 3‐year mortality, and factors related to mortality, in Scottish patients hospitalised with UC between 1998–2000 and 2007–2009. Methods The Scottish Morbidity Records and linked datasets were used to assess 3‐year mortality, standardised mortality ratio (SMR) and multivariate analyses of factors associated with 3‐year mortality. The 3‐year mortality was determined after four admission types: surgery‐elective or emergency; medical‐elective or emergency. Age‐standardised mortality rates (ASR) were used to compare mortality rates between periods. Results Ulcerative colitis admissions increased from 10.6 in Period 1 to 11.6 per 100 000 population per year in Period 2 (P = 0.046). Crude and adjusted 3‐year mortality fell between time periods (crude 12.2% to 8.3%; adjusted OR 0.59, CI 0.42–0.81, P = 0.04). Adjusted 3‐year mortality following emergency medical admission (OR 0.58, CI 0.39–0.87, P = 0.003) and in patients >65 years (38.8% to 28.7%, P = 0.02) was lower in Period 2. The SMR in period 1 was 3.04 and 2.96 in Period 2. Directly age‐standardised mortality decreased from 373 (CI 309–437) to 264 (CI 212–316) per 10 000 person‐years. On multivariate analysis, increasing age (50–64 years OR 7.11 (CI 2.77–18.27, P 75 years OR 46.42 (CI 18.29–117.78, P < 0.001) and co‐morbidity (OR 3.02, CI 1.72–5.28, P < 0.001) were significantly associated with 3‐year mortality in Period 2. Conclusions Comparisons of crude and adjusted mortality rates suggest significant improvement in outcome over the last decade – however, mortality remains high, and older age and co‐morbidity are important predictors of outcome