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World J Gastroenterol. Aug 21, 2022; 28(31): 4263-4298
Published online Aug 21, 2022. doi: 10.3748/wjg.v28.i31.4263
Evidence-based pathogenesis and treatment of ulcerative colitis: A causal role for colonic epithelial hydrogen peroxide
Jay Pravda
Jay Pravda, Disease Pathogenesis, Inflammatory Disease Research Centre, Palm Beach Gardens, FL 33410, United States
Author contributions: Pravda J is the sole author of this manuscript and solely responsible for its content; Pravda J performed all the research, collected, analyzed, and interpreted all the data; Pravda J conceived of and developed the hydrogen peroxide-based pathogenesis of ulcerative colitis; Pravda J prepared and wrote the manuscript and performed all critical revisions; Pravda J certifies that this manuscript is the product of his original research; and Pravda J has overall responsibility for this manuscript.
Conflict-of-interest statement: The author reported no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Jay Pravda, MD, Research Scientist, Senior Researcher, Disease Pathogenesis, Inflammatory Disease Research Centre, 4371 Northlake Blvd No. 247, Palm Beach Gardens, FL 33410, United States.
Received: January 25, 2022
Peer-review started: January 25, 2022
First decision: April 10, 2022
Revised: April 19, 2022
Accepted: July 20, 2022
Article in press: July 20, 2022
Published online: August 21, 2022

In this comprehensive evidence-based analysis of ulcerative colitis (UC), a causal role is identified for colonic epithelial hydrogen peroxide (H2O2) in both the pathogenesis and relapse of this debilitating inflammatory bowel disease. Studies have shown that H2O2 production is significantly increased in the non-inflamed colonic epithelium of individuals with UC. H2O2 is a powerful neutrophilic chemotactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular “trail” that attracts adjacent intravascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC. A novel therapy aimed at removing the inappropriate H2O2 mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one (biopsy-proven) histologic remission lasting 14 years to date. The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H2O2 mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease. Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects. It is the aim of this paper to present experimental and clinical evidence that identifies H2O2 produced by the colonic epithelium as the causal agent in the pathogenesis of UC. A detailed explanation of a novel therapeutic intervention to normalize colonic H2O2, its rationale, components, and formulation is also provided.

Keywords: Ulcerative colitis, Pathogenesis, Treatment, Hydrogen peroxide

Core Tip: Ulcerative colitis (UC) is a chronic inflammatory bowel disease that has resisted all efforts to uncover its cause and cure. However, an evidence-based systems medicine approach has provided compelling evidence that the secretion of hydrogen peroxide (H2O2) from colonic epithelial cells is the etiological agent responsible for this debilitating illness. H2O2 is a highly potent chemotactic agent that can attract neutrophils into the colonic epithelium, and significantly elevated production of H2O2 has been documented in the non-inflamed colonic epithelium of individuals with UC. Treatment to normalize colonic H2O2 leads to long-lasting histologic remission.