Comparative analysis of the pathogenesis in Crohn’s disease and ulcerative colitis

Abstract

This article discusses Yang and Zhang’s review on Crohn’s disease and ulcerative colitis pathogenesis, emphasizing immune dysregulation, genetics, microbiota, and environmental factors. It highlights the need for personalized approaches, longitudinal studies, and better diagnostic tools to improve treatment strategies and patient outcomes in inflammatory bowel disease.

Key Words: Inflammatory bowel diseases; Immunology; Microbiota; Crohn’s disease; Ulcerative colitis

Core Tip: This article highlights Yang and Zhang’s comprehensive review of Crohn's disease and ulcerative colitis pathogenesis, emphasizing immune dysregulation, genetics, microbiota imbalance, infections, and environmental factors. It underscores the need for personalized therapies, improved diagnostic tools, and longitudinal studies to better understand and manage inflammatory bowel disease.

TO THE EDITOR

We read with interest the minireview by Yang and Zhang[1], “Comparative study on the pathogenesis of Crohn’s disease and ulcerative colitis” published in the World Journal of Gastroenterology. Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic condition characterized by inflammation of the gastrointestinal tract. Despite decades of research, the precise mechanisms underlying IBD remain complex, involving an interplay of genetic, immune, microbial, and environmental factors. As the global prevalence of IBD continues to rise, understanding the pathogenesis of CD and UC is crucial for the development of more effective treatments and personalized approaches. In recent years, there have been significant advancements in the understanding of IBD’s pathogenesis, especially with respect to the role of genetic, immune, and microbiome factors. New insights, particularly in immunotherapy and microbiome science, have helped define personalized treatment approaches for IBD patients.

Pathogenesis of IBD: A multidimensional approach

The pathogenesis of IBD is driven by a confluence of six primary domains: Immune dysregulation, genetic susceptibility, microbial imbalance, infections, associations with other inflammatory conditions, and environmental/Lifestyle influences. Immune dysregulation in IBD leads to an exaggerated inflammatory response, primarily mediated by cytokines such as interleukin (IL)-22, IL-17, and T helper type 17 (Th17) cells, which play key roles in both CD and UC. Genetic factors, such as mutations in nucleotide-binding oligomerization domain 2 and IL-23 receptor, predispose individuals to immune dysfunction and an increased risk of developing IBD. These genetic predispositions interact with microbial imbalances in the gut, where shifts in microbiota contribute to disease progression. Infections, particularly viral and bacterial agents, can act as triggers for the inflammatory response in genetically predisposed individuals. Furthermore, the link between IBD and other inflammatory conditions, such as psoriasis and arthritis, underscores the systemic nature of the disease. Environmental factors, such as urbanization, diet, and hygiene, interact with these elements to modulate disease onset and severity, highlighting the complex relationship between host and environment[2]. This complex interaction between the immune system, genetics, and the microbiome has been further elucidated by recent studies, which emphasize the need for precision medicine to address IBD’s multifactorial nature.

The interplay of genetics, immunity, and microbes

IBD is a disease of complex origin, where host genetics, immune responses, and microbial factors do not function in isolation. Rather, they are intricately linked, creating a dynamic system in which each factor influences the others. For instance, genetic mutations can predispose individuals to an altered immune response, which is further influenced by microbial shifts in the gut. Environmental exposures, including diet, stress, and infections, can tip the balance of this system, exacerbating or ameliorating disease symptoms. This interconnection between genetics and immune responses is increasingly supported by recent research, which underscores the need for targeted therapies. This interconnectedness emphasizes the need for multifaceted treatments that target various aspects of disease pathogenesis[3].

Differences between CD and UC

Although CD and UC share many features in their pathogenesis, there are key differences in the immune responses, genetic mutations, and microbial profiles of each disease. CDs are primarily driven by a Th1 and Th17 cell response, while UC tends to have a Th2-dominated immune profile. The microbiota in CD is typically less diverse, whereas UC shows specific changes in microbial composition. These differences necessitate tailored treatment approaches for each disease, highlighting the importance of precision medicine in IBD management. Recent studies from 2020-2025 indicate promising developments in personalized treatments, particularly in targeting the immune response and microbiome interactions[4,5].

Conclusion and clinical applicability

The understanding of IBD pathogenesis has evolved into a multifactorial model, incorporating genetics, immunity, microbiota, and environmental factors. This model is not only important for understanding the underlying mechanisms but also for developing personalized treatment strategies. Precision medicine, which takes into account an individual’s genetic profile, microbial composition, and environmental factors, will likely lead to more effective, targeted therapies. Advances in biomarker development, particularly those related to immune and microbial signatures, will further enable clinicians to tailor treatments, improving patient outcomes and minimizing adverse effects. Recent research has shown that these personalized strategies have the potential to significantly improve patient outcomes and reduce the need for trial-and-error approaches in treatment[6].