What Actually Causes IBD? A Mechanistic Reading of Crohn's Disease and Ulcerative Colitis — Why this mechanism explains the clinical patterns better than the standard model

The standard immunologic model of IBD predicts that immunosuppression should produce durable remission, that response should be relatively predictable, and that surgical removal of diseased tissue should be curative for Crohn's disease (which involves discrete segments) and for ulcerative colitis (where colectomy removes the entire involved organ). The data do not support these predictions. Approximately 30 percent of patients do not respond to first-line biologics. Approximately 40 to 50 percent lose response over five years. Post-operative recurrence in Crohn's disease occurs in approximately 50 percent of cases within twelve months despite complete resection of all macroscopically diseased tissue. Pouchitis develops in approximately 50 percent of UC patients after restorative proctocolectomy with ileal pouch-anal anastomosis. These are not the patterns predicted by a model that locates the lesion in a specific tissue or in a specific immune circuit. These are the patterns predicted by a model that locates the lesion in the bioenergetic state of the surviving epithelium. When surgery removes the diseased segment, the remaining epithelium often shares the same bioenergetic compromise. The post-surgical anastomosis recurs because the new epithelial surface adjacent to the resection is still the bioenergetically compromised tissue that produced the original disease. The pouch be