From the Guidelines
Inflammatory Bowel Disease (IBD) is primarily driven by an abnormal immune response to gut microbiota, triggered by genetic predisposition and environmental factors, leading to a complex interplay of immune cells, cytokines, and tissue damage. The mechanism of IBD involves a multi-step process that starts with the disruption of the intestinal epithelial barrier, allowing bacterial antigens to penetrate the mucosa and trigger an inflammatory response 1. This response is mediated by pattern recognition receptors, such as Toll-like receptors, which recognize bacterial antigens and activate dendritic cells to present them to T cells. The T cells then differentiate into pro-inflammatory cells, including Th1, Th17, and Th2 cells, which release cytokines like TNF-α, IL-6, IL-17, and IL-23, recruiting additional inflammatory cells and causing tissue damage.
Key factors that contribute to the development and progression of IBD include:
- Genetic mutations, such as NOD2 mutations, which impair bacterial sensing
- Environmental triggers, such as diet, stress, and medications
- Disruption of the intestinal epithelial barrier
- Abnormal immune response to gut microbiota
- Release of pro-inflammatory cytokines and recruitment of inflammatory cells
The understanding of these mechanisms is crucial for the development of effective treatments, such as anti-TNF biologics, JAK inhibitors, and anti-integrin therapies, which target specific parts of the IBD pathway. Additionally, dietary approaches, such as lactose-reduced, FODMAP-reduced, gluten-free, and specific-carbohydrate diets, may help alleviate symptoms in some patients by reducing the intake of indigestible and slowly absorbed carbohydrates that can induce symptoms through luminal distension and mechanoreceptor stimulation 1. However, it is essential to consider the potential adverse effects of restrictive diets, particularly in conditions where undernutrition is common, and to ensure nutritional adequacy through dietary instruction by a dietitian.
From the Research
Mechanism of IBD
- Inflammatory Bowel Diseases (IBD) are chronic nonspecific intestinal inflammatory diseases with a relapsing-remitting course, including Ulcerative Colitis (UC) and Crohn's Disease (CD) 2.
- The exact mechanism of IBD is not fully understood, but it is believed to involve a combination of genetic, environmental, and immune system factors.
Treatment of IBD
- Conventional treatments for IBD aim to control symptoms through pharmacotherapy, including aminosalicylates, corticosteroids, immunomodulators, and biologics, with other general measures and/or surgical resection if necessary 3.
- Aminosalicylates, such as sulphasalazine and mesalamine, have anti-inflammatory and immunomodulatory properties and are used to treat acute inflammatory bowel disease and maintain clinical remission 4, 5.
- Combination therapy, including the combination of infliximab and thiopurines, has been shown to be more effective than monotherapy in inducing and maintaining remission in IBD 2, 6.
Combination Therapy
- Combination therapy has been proposed as a strategy to enhance treatment efficacy in IBD, particularly in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives 2, 6.
- Dual Targeted Therapy, which is the combination of two biological agents and/or small molecules, may be a reasonable choice in selected patients, but it is associated with an increased risk of adverse events and malignancies 2, 6.