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Herein, we provide a comprehensive overview of current gaps in inflammatory bowel diseases research that relate to preclinical research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in IBD interception, remission, and restoration. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. This preclinical human IBD mechanisms section identifies major research gaps whose investigation will elucidate pathways and mechanisms that can be targeted to address unmet medical needs in IBD. Research gaps were identified in the following areas: genetics, risk alleles, and epigenetics; the microbiome; cell states and interactions; barrier function; IBD complications (specifically fibrosis and stricturing); and extraintestinal manifestations. To address these gaps, we share specific opportunities for investigation for basic and translational scientists and identify priority actions.<\/jats:p>","DOI":"10.1093\/ibd\/izae081","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T08:38:51Z","timestamp":1716453531000},"page":"S5-S18","source":"Crossref","is-referenced-by-count":38,"title":["Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms"],"prefix":"10.1093","volume":"30","author":[{"given":"Matthew A","family":"Ciorba","sequence":"first","affiliation":[{"name":"Inflammatory Bowel Diseases Center, Division of Gastroenterology, Washington University in St. Louis , Saint Louis, MO ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"Konnikova","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Immunobiology, and Obstetric, Gynecology and Reproductive Sciences, Yale School of Medicine , New Haven, CT ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A","family":"Hirota","sequence":"additional","affiliation":[{"name":"Snyder Institute for Chronic Diseases, Dept. of Physiology and Pharmacology, University of Calgary , Calgary, Alberta ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena M","family":"Lucchetta","sequence":"additional","affiliation":[{"name":"The Leona M. and Harry B. 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