What Actually Causes IBD? A Mechanistic Reading of Crohn's Disease and Ulcerative Colitis — The clinical pattern that defines treatment-resistant IBD

A patient presents to a gastroenterologist with bloody diarrhea, abdominal pain, weight loss, urgency, and fatigue. Colonoscopy reveals continuous mucosal inflammation of the colon (ulcerative colitis) or discontinuous transmural inflammation that may involve any portion of the gastrointestinal tract (Crohn's disease). The patient is started on an aminosalicylate (5-ASA) for mild-to-moderate disease, or a corticosteroid for active flare, or a biologic (anti-TNF agents like infliximab and adalimumab, anti-integrin agents like vedolizumab, anti-IL-12/23 agents like ustekinumab, or the newer JAK inhibitors and S1P modulators) for moderate-to-severe disease. Many patients respond. The inflammation reduces. The bleeding stops. The bowel movements normalize. The patient enters clinical remission. For some, this remission is sustained. For many, it is partial. For a substantial fraction, the response is lost over time. The literature documents primary non-response rates of approximately 30 percent for biologics and secondary loss of response rates of approximately 40 to 50 percent over five years of follow-up. Post-operative recurrence in Crohn's disease is approximately 50 percent within twelve months of ileocolic resection, even when the macroscopic disease has been entirely removed. The standard interpretation of these patterns is that IBD is a relapsing-remitting immune-mediated d