# Paneth Cells and Lgr5+ Intestinal Stem Cells in Radiation Enteritis
###### Abstract  
Cancer is the leading cause of death in adults and majority of cancers involve abdominal and pelvic organs. Radiotherapy is used in the management of around half of patients who have abdominal and pelvic malignancies and 70% of the treated patients will develop radiation enteritis. The onset of radiation enteritis may delay the completion of treatment or lead to life-threatening conditions such as bowel perforation or obstruction. High-dose ionizing radiation can affect all the layers of the small intestine leading to weakening of its structural integrity, dysbiosis, malabsorption, and derangement of the innate immunity. Advances in the management of cancer has not led to an improvement in the treatment of radiation enteritis as the available preventative or treatment options are still ineffective. Severe acute and chronic radiation enteritis result from the damage to the crypt-based intestinal stem cells and their derivatives, which include the Paneth cells. Paneth cells regulate the proliferation and differentiation of the intestinal stem cells. The other roles of the Paneth cells are protection and nonurishment of the intestinal stem cells, and control of the gut microbiota. Paneth cells can also de-differentiate and replace irreversibly damaged intestinal stem cells. This article reviews the anatomy of the epithelium of the small intestine and the intestinal epithelial cells including the Paneth cells. The effect of ionizing radiation on the intestinal stem cells and its derivatives, and the knowledge can be used to develop effective treatment of radiation enteritis is discussed. complications; intestinal stem cells; Paneth cells; radiation enteritis; radiotherapy; treatment +
Footnote †: journal: Medical  
for instance following ionizing radiation [11; 21; 22]. The process of de-differentiation and replacement of the Lgr5\({}^{+}\) ISCs is normally led by the reserve ISCs and Paneth cells, and the other intestinal epithelial cells (IECs) only get activated by the Paneth cells that have also been irreversibly damaged [11]. The other roles of the Paneth cells in the small intestine are to protect, nourish, and regulate proliferation and differentiation of the Lgr5\({}^{+}\) ISCs [14; 23; 24; 25; 26]. The Lgr5\({}^{+}\) ISCs use lactate which is produced in the adjacent Paneth cells for their energy production. Additionally, Paneth cells monitor and regulate the microbiota in the lumen of the small intestine [27; 28; 29; 30; 31]. Paneth cells provide the link between the innate immunity and adaptive immunity of the in the gut, and ultimately of the entire body [11; 27; 28; 29; 30; 31]. The most common side effects of radiotherapy to abdominal or pelvic organs is radiation enteropathy/radiation enteritis (RE) [32]. The risk factors of RE include age above 60 years, smoking, diabetes mellitus, hypertension, connective tissue disorders, HIV status, previous abdominal surgery, hypo-albuminemia and concurrent administration of chemotherapy with radiotherapy [9; 32]. Radiation enteritis can occur within days or many years following treatment. Acute RE usually manifest within 10 days and its pathological features include oedema of the bowel wall, mucositis, ulceration, perforation, necrosis of small bowel, or death within days. Chronic RE presents after 6 months following radiotherapy and is due to vasculitis and chronic fibrosis. The ongoing fibrosis in chronic RE may lead to stricture formation and mechanical small bowel obstruction [33; 34]. The other complications of chronic RE are internal fistulae, dysbiosis, and malabsorption syndromes [35]. The occurrence of either acute and chronic RE may lead to a delay in the completion of treatment or affects the quality of life of a patient even in cases where the cancer is cured. The prevention, amelioration, and management of RE have remained a challenge ever since the discovery and use of radiotherapy in the treatment of cancer in 1897.