Challenges in IBD research: Update on progress and prioritization of the CCFA's research agenda

The Crohn's and Colitis Foundation of America (CCFA) convenes meetings of leading basic, translational, and clinical researchers every 4 to 5 years to update progress on the foundation's research agenda and prioritize goals in inflammatory bowel diseases (IBDs) research. These multidisciplinary meetings are designed to identify crosscutting goals across basic and clinical research arenas. The goal of each meeting is to define the overarching integrative global research mission and priorities of the CCFA for the ensuing 4 to 5 years. The first such meeting was in 1990, at which time a white paper entitled "Challenges in IBD Research" was produced naming research priorities and resources necessary to reach these goals. Updated "Challenges" documents have been produced at regular intervals since this time. The most recent Challenges document was published in 2008. This document described advances in basic and clinical research for the preceding interval years and identified major themes in research priorities to emphasize in the near future. During this interval, advances were made in identification of genes, in understanding the association between IBD and abnormal host responses to commensal bacterial flora, in the contribution of the innate immune system to mucosal homeostasis, and elucidation of the cellular populations and their mediators that drive and regulate immune responses. This document identified important themes for research priorities from 2008 to 2012, including improved tools for rapid identification of genes associated with IBD, enhanced tools for microbiome analysis, genetically determined variances in responses to drugs and prognosis, and improvement in therapeutic options for IBD management. In June 2012, leading researchers representing committees composed of multidisciplinary investigators drawn from a variety of research areas relevant to IBD pathogenesis and treatment convened to review progress since the last document and identify new global research priorities for the CCFA. The group concluded that since 2008, advances in basic research have principally included: • Significant and rapid progress has been made in identifying additional genetic loci in Crohn's disease (CD) and ulcerative colitis (UC), with over 160 published susceptibility loci/genes to date. • Fundamental insights into enteric microbiota community structure and genetic, immunologic, and microbial interactions have been made possible through rapid advances in high-throughput DNA sequencing and bioinformatics technology. These tools have allowed for identification of immunologic properties of individual species and groups of bacteria and have provided evidence that hostassociated bacterial communities are more complex in their interactions and biochemistry than previously thought. • The interaction of the intestinal microbiota and innate immune cells with the mucosal adaptive immune system has been shown to play an important and required role for the development of Th17 and regulatory T cells. • There has been further discovery of novel functions and regulation for previously recognized innate immune cells, and the discovery and characterization of novel innate immune cell types such as innate lymphoid cells. Significant advances in clinical research have also occurred, with the following major themes: • Large cohort studies have been initiated to identify clinical or biological variables that predict treatment outcome and risk stratification in pediatric IBD (e.g., RISK Stratification Study and Predicting Response to Standardized Pediatric Colitis Therapy "PROTECT"). • Multicenter registries have been developed to determine the incidence of short-term and long-term adverse effects of medical therapies used to treat pediatric IBD. • Prospective cohort studies have provided a better understanding of risks and benefits of medical and surgical therapies in key subpopulations (e.g., Pregnancy in IBD and Neonatal Outcomes study "PIANO"). Based on these advances in the past 5 years, with further understanding of disease pathogenesis and therapy, leading researchers developed a new research agenda for the CCFA. This agenda is divided into 8 subgroups with a discrete research agenda for each section. These sections include genetics, epidemiology and environmental factors, microbiome, epithelial cell biology, innate immunity, adaptive immunity, IBD diagnoses, and optimizing medical therapy.