Abstract There is growing recognition that inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is preceded by a prolonged preclinical phase marked by subtle but measurable changes in the immune system, gut microbiome, and epithelial barrier function. These early alterations, often detectable years before diagnosis, offer a window of opportunity for disease interception. In this review, we examine the current evidence for environmental, microbial, and molecular factors that may contribute to the initiation of IBD, with a particular focus on modifiable risk pathways. We discuss preventive strategies across different levels of risk—from lifestyle and environmental interventions in the general population to more targeted approaches in individuals with familial predisposition, such as first-degree relatives. We also highlight recent findings on emerging biomarkers, including anti-flagellin antibodies, anti-GM-CSF autoantibodies, glycome, and integrin-targeted immune responses, that could guide precision prevention efforts. While most evidence to date has focused on CD, we also review preclinical insights relevant to UC. As the field moves toward earlier identification of at-risk individuals, the concept of “precision prevention”—matching interventions to individual risk and biology—may ultimately shift the paradigm of IBD care from treatment to prevention.
Lee et al. (2025) studied this question.