What Actually Causes IBD? A Mechanistic Reading of Crohn's Disease and Ulcerative Colitis — Selected primary research

The mechanisms described in this article are drawn from primary research published over the past three decades. Key references include: Roediger WEW. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980;2(8197):712-715. Donohoe DR, Garge N, Zhang X, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metabolism. 2011;13(5):517-526. Litvak Y, Byndloss MX, Tsolis RM, Bäumler AJ. Dysbiotic Proteobacteria expansion: a microbial signature of epithelial dysfunction. Curr Opin Microbiol. 2017;39:1-6. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008;105(43):16731-16736. Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011;474(7351):307-317. These references are starting points. The literature on colonocyte bioenergetics and IBD has expanded substantially in the past decade. The framework described in this article synthesizes findings across this literature into a clinical interpretation that has not yet been formalized in mainstream gastroenterology practice.