Inflammatory Bowel Disease: A Comprehensive Analysis of Molecular Bases, Predictive Biomarkers, Diagnostic Methods, and Therapeutic Options

Abstract

In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.

Keywords: Crohn’s disease; antibodies; biomarkers; environmental; genetic; immunity; inflammatory bowel disease; microbiota; molecular mechanisms; therapeutic targets; ulcerative colitis.

Figure 1

Prevalence (left) and incidence (right) trends from 1990 to 2019. Charts acquired from Global Burden of Disease (GDB).

Figure 2

Most relevant immunological, genetic, environmental, and microbiota influences.

Figure 3

Overview of key inflammatory events initiating inflammation. Initially, environmental, genetic, and immunological factors disrupt the intestinal epithelial barrier, allowing microbiota entry into the lamina propria and triggering an inflammatory cascade. Dendritic cells (DCs) and macrophages recognize pathogens, presenting antigens to T and B cells, resulting in cytokine release. In Peyer’s patch, a gut-associated lymphoid tissue (GALT), DCs stimulate Th0 cell differentiation into specific T cell subtypes based on environmental cytokines. B cells produce elevated levels of immunoglobulins (Igs) A and G in the intestinal lumen, while natural killer (NK) cells promote autophagy and apoptosis.