What is enteropathy?

Enteropathy is a broad term used to describe any disease or disorder affecting the intestines, particularly the small intestine. It refers to a variety of conditions characterized by inflammation, damage, or dysfunction of the intestinal mucosa (the inner lining of the intestine) and may involve various underlying causes, including infections, immune reactions, genetic factors, dietary factors, and medication use.


There are several types of enteropathy, each with its own distinct features and clinical manifestations:


  • Inflammatory Bowel Disease (IBD): Enteropathy encompasses inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, which are chronic inflammatory conditions of the gastrointestinal tract. These conditions are characterized by periods of active inflammation and remission, and they can lead to symptoms such as abdominal pain, diarrhea, rectal bleeding, weight loss, and fatigue.


  • Celiac Disease: Celiac disease is an autoimmune disorder triggered by the ingestion of gluten, a protein found in wheat, barley, and rye. In individuals with celiac disease, the immune system mistakenly attacks the lining of the small intestine in response to gluten consumption, leading to inflammation and damage to the intestinal villi (small finger-like projections that absorb nutrients). This can result in malabsorption of nutrients, diarrhea, abdominal pain, bloating, and other gastrointestinal symptoms.


  • Infectious Enteropathy: Enteropathies can also be caused by various infectious agents, including bacteria (e.g., Salmonella, Campylobacter, Escherichia coli), viruses (e.g., norovirus, rotavirus), and parasites (e.g., Giardia, Cryptosporidium). These infections can lead to acute or chronic inflammation of the intestinal mucosa, resulting in symptoms such as diarrhea, abdominal cramps, nausea, vomiting, and fever.


  • Radiation Enteropathy: Radiation therapy used in the treatment of cancer can cause damage to the intestinal mucosa, leading to radiation enteropathy. Chronic exposure to ionizing radiation can impair the regeneration of intestinal cells, disrupt mucosal integrity, and result in inflammation, fibrosis, and vascular damage within the intestine. Radiation enteropathy can cause symptoms such as diarrhea, abdominal pain, bloating, and malabsorption of nutrients.


  • Drug-Induced Enteropathy: Certain medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), antibiotics, and immunosuppressants, can cause enteropathy as a side effect. These medications may disrupt the balance of gut microbiota, alter intestinal permeability, or directly damage the intestinal mucosa, leading to inflammation, ulceration, or other gastrointestinal symptoms.


What is the relationship between enteropathy and oxidative stress?

The relationship between enteropathy and oxidative stress involves complex interactions between inflammatory processes, reactive oxygen species (ROS) production, and tissue damage within the intestine. Here’s how oxidative stress influences enteropathy:


  • Inflammation: Enteropathy is often associated with inflammation of the intestinal mucosa, which can be triggered by various factors such as infections, autoimmune reactions, dietary factors, and medication use. Inflammatory processes within the intestine can lead to the activation of immune cells, release of inflammatory cytokines, and recruitment of leukocytes to the site of injury. These inflammatory responses contribute to oxidative stress by inducing the production of ROS and reactive nitrogen species (RNS) by immune cells such as neutrophils, macrophages, and epithelial cells.


  • Immune Dysregulation: Oxidative stress can disrupt immune homeostasis within the intestine by modulating the function of immune cells and altering the balance between pro-inflammatory and anti-inflammatory pathways. ROS/RNS generated during oxidative stress can activate nuclear factor kappa B (NF-κB) and other transcription factors involved in inflammatory signaling pathways, leading to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). Chronic inflammation and immune dysregulation contribute to tissue damage, impaired barrier function, and the progression of enteropathy.


  • Tissue Damage: Oxidative stress-induced damage to cellular components such as lipids, proteins, and DNA can compromise the integrity of the intestinal mucosa and disrupt normal tissue structure and function. ROS can induce lipid peroxidation, a process in which polyunsaturated fatty acids in cell membranes are oxidized, leading to membrane damage and cell lysis. Protein oxidation and nitration can impair the function of enzymes, receptors, and structural proteins, further exacerbating tissue injury and dysfunction. DNA damage caused by ROS/RNS can lead to mutations, apoptosis, and impaired cellular repair mechanisms, contributing to the pathogenesis of enteropathy.


  • Barrier Dysfunction: Oxidative stress can disrupt the integrity of the intestinal epithelial barrier, leading to increased permeability and leakage of luminal contents into the underlying tissue. ROS/RNS can modulate the expression and localization of tight junction proteins, such as occludin, claudins, and zona occludens (ZO), which regulate paracellular permeability. Disruption of tight junctions and epithelial barrier function can promote translocation of bacteria, toxins, and antigens from the gut lumen into the lamina propria, triggering immune responses and inflammation. Chronic barrier dysfunction is associated with the development of enteropathy and may contribute to the pathogenesis of inflammatory bowel diseases, celiac disease, and other intestinal disorders.


Overall, oxidative stress plays a significant role in the pathogenesis of enteropathy by promoting inflammation, immune dysregulation, tissue damage, and barrier dysfunction within the intestine.