What Actually Causes IBD? A Mechanistic Reading of Crohn's Disease and Ulcerative Colitis — What Roediger discovered in 1990 and why it matters

In 1990, the Lancet published a paper by William Roediger titled "The colonic epithelium in ulcerative colitis: an energy-deficiency disease?" The paper made a specific claim. Colonocytes from patients with ulcerative colitis have reduced capacity to oxidize butyrate compared to colonocytes from healthy controls. The reduction is substantial. Roediger called UC an "energy-deficiency disease" of the colonic epithelium. The paper was largely ignored by the mainstream gastroenterology research community for the following two decades. The field was committed to an immunologic framing of IBD, in which abnormal immune response to luminal contents was the central lesion. The colonocyte bioenergetic angle was relegated to a footnote. Subsequent research has supported and extended Roediger's finding. Studies by Donohoe and colleagues, Bäumler and colleagues, Litvak and colleagues, and others have documented that colonocyte mitochondrial dysfunction is present in active IBD, that the dysfunction is mechanistically connected to the loss of obligate anaerobic core taxa, that the resulting shift in luminal oxygen tension allows facultative anaerobes (Enterobacteriaceae and others) to expand, and that this expansion is itself inflammatory. The complete story is now well-characterized in the primary literature. It has not yet propagated into clinical practice. The mechanism is this. The healt