CENTER OVERVIEW: PROJECT SUMMARY The goal of the Center for the Study of Inflammatory Bowel Disease (CSIBD) is to promote and facilitate digestive disease research that yields insight into IBD pathogenesis and leads to therapeutic advancements. This objective remains unchanged since the inception of the CSIBD in 1991, guiding the Center through nearly three decades of discovery in genetic underpinnings of IBD risk and protection, mechanisms of epithelial and immune function, and contributions to etiology from the gut microbiome. The CSIBD is home to 89 members that received over $44 million in digestive disease research funding. CSIBD research is driven by a central hypothesis that the major forms of IBD result from interactions between genetically-determined and permissive features of the individual, gut microbiome, and other environmental factors that dysregulate intestinal immune and inflammatory pathways. Investigations are broadly divided into six areas: human genetics and physiological mechanisms; the gut microbiome in health and disease; cell circuits and systems biology; innate and adaptive immunity; chemical biology and therapeutic science; and clinical translational science and patient impact. Collaborations within the CSIBD generated a single-cell atlas of the human colon during ulcerative colitis (UC) that revealed new inflammatory populations associated with disease and anti-TNF therapy resistance, pinpointed cell types in which UC susceptibility genes function, and established a framework for elucidating mechanisms of inflammation and treatment response. Incorporating longitudinal microbiome metagenomic, metatranscriptomic, and metabolomic profiles with host molecular measurements, the Integrative Human Microbiome Project catalogued host–microbe relationships in IBD and laid a foundation for the next phase in clinical translation of the gut microbiome. The overall specific aims of the CSIBD are to (1) promote research in basic science areas relevant to better understanding of epithelial biology and mucosal immune function in IBD; (2) advance our understanding of gut pathophysiology by examining the gut as a circuit, studying the core components of gut intra- and inter-cellular interactions that determine health and disease; (3) promote the study of the pathogenesis of IBD; (4) promote interactions among scientists exploring diverse fields that share relevance to IBD; (5) promote translational IBD research; (6) attract investigators to the study of IBD and mucosal immunology; and (7) provide an environment and mechanism to foster development of young investigators focused on IBD. A central priority of the CSIBD is to serve as a nexus of fundamental science, clinical translation, and patient benefit by enabling collaborations across biomedical disciplines and catalyzing advancements that address critical barriers to building a more detailed understanding of IBD and its causes. Four biomedical cores offer state-of-the-art resources and...