Breaking Down the Gut Barrier: Cytokine-Mediated Epithelial Dysfunction as a Hallmark of Inflammatory Bowel Disease Progression

Abstract

The intestine plays a vital role not only as the main organ for absorbing nutrients and water but also as a crucial barrier protecting the body from harmful and toxic substances, often introduced through daily dietary intake [1]. With a total surface area of about 400 m², the gastrointestinal (GI) tract is home to an estimated 10¹⁴ microorganisms. This microbial community outnumbers human cells by a factor of 10 and contains over 100 times the genetic material found in the human genome. Under normal circumstances, this microbiota offers significant benefits, including protecting against harmful pathogens and helping to regulate the immune system [2]. However, changes in the composition of gut bacteria, known as dysbiosis, can disrupt the balance of intestinal homeostasis. This disruption occurs through altered signaling pathways, ultimately affecting how the bacteria interact with the host [3]. Gut bacteria are crucial for breaking down indigestible carbohydrates to produce short-chain fatty acids (SCFAs), synthesizing essential vitamins like B12, K, and folate, and regulating lipid metabolism. These functions are vital for maintaining the integrity of the intestinal barrier. In addition to supporting metabolism, gut bacteria protect the intestinal lining by preventing the colonization of harmful pathogens and producing antimicrobial compounds, ensuring a stable gut environment [4]. Moreover, the gut microbiota actively supports the development and maturation of the immune system, which is essential for defending against infections and maintaining tolerance to harmless substances in the gut [5]. While the gut microbiota is generally beneficial, not all bacteria are harmless. For instance, Bacteroides fragilis, typically a well-behaved commensal, can invade intestinal tissues and cause significant problems in individuals with weakened immune systems. ...