**3. Paneth cells and diseases**

Paneth cells are involved in the fight against and pathogenesis of diseases. Paneth cells' effect on diseases is evidenced by changes in their granules, the total number, position, or distribution pattern. The health status of Paneth cells is assessed by checking their presence, position, number and intensity of staining of their granules [3, 10, 15, 27, 34, 38, 39]. The integrity of the intestinal epithelium is assessed directly by measuring the depth of the intestinal crypt, the height of the villi, mitotic count [27], Ki67 index, markers of apoptosis and epithelial integrity as evidenced by, for example; the presence of bacteria inside intestinal epithelial cells and translocation. Dysbiosis is one of the key steps in the pathogenesis of many medical and surgical diseases [19, 40]. Translating bacteria and endotoxins induces an immune response leading to a systemic inflammatory response. Immune activation and resulting systemic inflammation are deleterious to the body as it has been proven to be the underlying reason behind most metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, and obesity. Chronic immune activation and systemic inflammation are paradoxically the major drivers of complications associated with chronic HIV infection regardless of treatment with antiretroviral drugs [41–45]. A chronic inflammatory state is one of the main reasons why HIV currently can neither be cured nor eradicated.

Duodenal Paneth cells are reduced in individuals with idiopathic autoimmune enteropathy [21]. Cells with the characteristic of the Paneth cells and goblet cells, the so-called intermediate cells, may appear high up in the intestinal epithelium crypt above position eight in patients with inflammatory bowel disease [46]. The number and size of paneth cells are increased in individuals who have autism with gastrointestinal tract symptoms [47]. Among the conditions which are associated with dysbiosis and increased permeability of the intestinal epithelium are chronic HIV/AIDS [2, 42, 43, 48–53] and HIVlinked surgical conditions such as necrotizing enterocolitis [54], obstructive jaundice, inflammatory bowel disease [55–57], obesity [40, 58, 59] fasting and prolonged total parenteral nutrition [3, 38]. The above conditions have either been proven or are possibly linked to dysfunction of Paneth cells in the small intestine.

Diseases that have been conclusively linked with change in the appearance of paneth cells include necrotizing enterocolitis [1, 60], starvation [38] prolonged total parenteral nutrition [3], inflammatory bowel disease [7, 20, 36], mesenteric ischaemia, radiation enteritis [61], coeliac disease [27], colorectal carcinoma [62], autism [47] and HIV infection [63–65]. The other evidence of ill health in the gut include atrophy of small bowel mucosa, the appearance of defects in the mucosa, translocation of bacteria and toxins, systemic sepsis and development of inflammatory bowel diseases or the appearance of malignant neoplasms. In this chapter, we illustrate the direct role played by the Paneth cells in their pathogenesis using the diseases below.

### **3.1 Necrotizing enterocolitis**

Current knowledge of the function of Paneth cells has enhanced the understanding of the crucial role in the pathogenesis of Necrotizing enterocolitis (NEC). NEC is a common condition that affects neonates and is manifested by acute inflammatory changes in the bowel wall. The risk factors of NEC include prematurity, low birth weight (<1.5Kg), formula feeding, antibiotic use and HIV status of the mother [2, 66]. Some studies attribute the pathogenesis of NEC to premature colonization of the gut in the neonate or an ischaemic event [60, 66–68]. Necrotizing

### *Paneth Cells: The Gatekeepers of the Gut DOI: http://dx.doi.org/10.5772/intechopen.104402*

enterocolitis is linked with untimely colonization of the gut when the gut immune system has not matured. A sufficient number of Paneth cells and their maturity only get established around the term. When they are well developed, Paneth cells can secrete an adequate amount of antimicrobial peptides, including HD5 and HD6, for innate immune defense. The switch from cathelicidins to defensins only occurs during the third trimester of pregnancy [60].

Consequently, preterm babies are prone to colonization by pathogenic organisms, followed by bowel invasion by pathogenic bacteria and inflammation. Early oral feeding of infants leads to dysbiosis, increased permeability, bacterial translocation, and an inflammatory state in the intestinal epithelium. The ongoing inflammation would then lead to ischaemia. The inflammatory process causes thrombosis of vessels in the submucosa and the lamina propria. In some cases, the initiating event for NEC is ischaemia and then inflammatory response. The most feared complication of NEC is bowel necrosis, leading to perforation and severe sepsis. In some cases of NEC, ischaemia is the initiating event. Both premature colonization and ischaemic events are associated with abnormality in the functioning of the Paneth cells [1, 60].
