Regulatory Mechanisms and Pathological Significance of Crohn’s Disease Focused on Recent Advancements: A Narrative Review

Abstract

Crohn’s disease is a multifactorial inflammatory bowel disease that involves genetic susceptibility, dysregulated immune responses, and environmental triggers. This study was a narrative review of the regulatory mechanisms and pathological significance of Crohn’s disease. Scientific databases were searched, including: PUBMED, Embase, Google Scholar, Web of Science, and Scopus. The studies considered were original research articles, meta-analyses, randomized controlled trials, and systematic reviews published between 2020 and 2026. A total of 118 articles were screened for eligibility (except those articles used during the ‘Introduction section’). A total of 98 articles were eligible, while 20 were ineligible. The articles reviewed provided information on the fundamental pathophysiology of Crohn’s disease and its regulatory mechanisms; genetic and molecular drivers; immune regulation and dysregulation; the microbiome and environmental factors; and emerging therapeutic targets and mechanisms. The fundamental pathophysiology and regulatory mechanisms identified include: intestinal barrier dysfunction, defective bacterial clearance, transmural inflammation and granuloma formation, fibrosis and stricture formation, and mesenteric fat hypertrophy. Other parameters highlighted were the microbiome and environmental factors, including dysbiosis of the gut microbiota, smoking, dietary factors, and vitamin D deficiency. Others were medications, psychological and environmental stress, infections, urbanization, pollution, and exposomes. New findings include: exposome-diet epigenome and E-cigarettes.  Emerging therapeutic targets and mechanisms were emphasized: anti-TNF/IL-12/IL-23 inhibitors, adhesion molecule inhibitors, restoring barrier formation, and mesentery-based surgery. Despite Crohn’s disease being studied extensively, and many pathophysiological and regulatory mechanisms elucidated, there has not been a radical cure for the ailment. This necessitated research and a consequent development of new treatment approaches.