Ulcerative colitis: Timeline to a cure

Abstract

Ulcerative colitis has baffled researchers since the early 20^th century. The prevailing explanation attributes the chronic recurring episodes of bloody diarrhea and abdominal pain to some form of immune abnormality, despite the lack of supporting evidence. This highlights the critical need for innovative research directions and methodologies to uncover the cause and develop a cure for this disease. By analyzing existing data from less than a dozen previously published studies, a novel, evidence-based pathogenesis was constructed, implicating colonic epithelial hydrogen peroxide as a causal factor in the development of this disease. This newly identified mechanism informed the creation of a groundbreaking class of therapeutics, known as reducing agents, which have demonstrated remarkable success in resolving colonic inflammation and restoring colonic health in patients with refractory ulcerative colitis. This paper outlines the timeline of these publications and reinterprets the findings within the context of contemporary biomedical science.

Keywords: Ulcerative colitis; Pathogenesis; Treatment; Hydrogen peroxide; Common pathway

Core Tip: Since the mid-20^th century, research into the causes of ulcerative colitis has predominantly focused on the immune system and microbiome, overlooking the colonic epithelium’s role in its pathogenesis. This conformation bias has delayed recognition of the causal role played by colonocyte hydrogen peroxide in the pathogenesis of this inflammatory bowel disease. Notably, fewer than a dozen studies since that time have laid the groundwork for this conclusion. This review critically examines these foundational studies through the lens of contemporary biomedical science, tracing their evolution toward the identification of a causal role for colonocyte hydrogen peroxide in the pathogenesis of ulcerative colitis.