Inflammatory Bowel Disease: From Multifactorial and Metabolic Pathogenesis to Systemic Disease and Precision Medicine

Introduction: Inflammatory bowel disease (IBD) is an umbrella term encompassing two major chronic immune-mediated disorders, Crohn’s disease (CD) and ulcerative colitis (UC). Its pathogenesis reflects complex interactions among genetic, microbial, metabolic, environmental, and immune factors. Growing evidence supports the concept of IBD as a systemic disease associated with intestinal dysbiosis, epithelial barrier dysfunction, metabolic alterations, and extraintestinal complications. However, these interconnected mechanisms and their systemic consequences are often examined separately, limiting an integrated understanding of IBD and its implications for individualized management. Accordingly, an updated synthesis linking intestinal, microbial, metabolic, immune, and systemic processes is needed to consolidate current evidence and support precision medicine. Methods: A narrative literature review was conducted using PubMed, Web of Science, and LILACS. The search strategy used controlled vocabulary terms indexed in Medical Subject Headings (MeSH) and Health Sciences Descriptors (DeCS), combined with Boolean operators. Studies addressing IBD epidemiology, pathophysiology, clinical manifestations, diagnosis, treatment, gut microbiota, microbial metabolites, and systemic complications were critically evaluated. Results: Current evidence indicates that dysbiosis and impaired intestinal barrier integrity are associated with alterations in microbial metabolites, including short-chain fatty acids, bile acids, lipids, and other microbiota-derived compounds. These alterations interact with immune and inflammatory pathways and may contribute to extraintestinal manifestations, particularly metabolic and hepatobiliary disorders through the gut–liver axis. Advances in metabolomics, multi-omics approaches, biologic agents, and targeted therapies are expanding opportunities for patient stratification and individualized treatment. Conclusions: IBD should be regarded as a systemic and multifactorial disorder involving interconnected microbial, metabolic, molecular, and immune mechanisms. Integrating these dimensions may improve disease monitoring, therapeutic selection, and the development of precision medicine strategies.