The Paneth Cell: The Curator and Defender of the Immature Small Intestine

Abstract

Paneth cells were first described in the late 19th century by Gustav Schwalbe and Josef Paneth as columnar epithelial cells possessing prominent eosinophilic granules in their cytoplasm. Decades later there is continued interest in Paneth cells as they play an integral role in maintaining intestinal homeostasis and modulating the physiology of the small intestine and its associated microbial flora. Paneth cells are highly specialized secretory epithelial cells located in the small intestinal crypts of Lieberkühn. The dense granules produced by Paneth cells contain an abundance of antimicrobial peptides and immunomodulating proteins that function to regulate the composition of the intestinal flora. This in turn plays a significant role in secondary regulation of the host microvasculature, the normal injury and repair mechanisms of the intestinal epithelial layer, and the levels of intestinal inflammation. These critical functions may have even more importance in the immature intestine of premature infants. While Paneth cells begin to develop in the middle of human gestation, they do not become immune competent or reach their adult density until closer to term gestation. This leaves preterm infants deficient in normal Paneth cell biology during the greatest window of susceptibility to develop intestinal pathology such as necrotizing enterocolitis (NEC). As 10% of infants worldwide are currently born prematurely, there is a significant population of infants contending with an inadequate cohort of Paneth cells. Infants who have developed NEC have decreased Paneth cell numbers compared to age-matched controls, and ablation of murine Paneth cells results in a NEC-like phenotype suggesting again that Paneth cell function is critical to homeostasis to the immature intestine. This review will provide an up to date and comprehensive look at Paneth cell ontogeny, the impact Paneth cells have on the host-microbial axis in the immature intestine, and the repercussions of Paneth cell dysfunction or loss on injury and repair mechanisms in the immature gut.

The 3D Pattern of the Rainbow Trout (Oncorhynchus mykiss) Enterocytes and Intestinal Stem Cells

“…Despite their fundamental role, the presence of bona fide Paneth cells has not been detected in many mammals and fish species including RT [5,11]. However, DLL1 is also expressed in mouse colon, where Paneth cells are absent [47]. Taken together, these observations suggest the hypothesis that, in those species where typical Paneth cells are not present, another cell type may functionally substitute them, actively interacting with ISCs.…”

Preterm birth and sustained inflammation: consequences for the neonate

“…Several exogenic factors (e.g., chronic ischemia during pregnancy, chorioamnionitis, antibiotic exposure, parenteral nutrition) trigger dysbiosis and seem relevant for the risk of inflammation-mediated acute gut complications (e.g., NEC). In pregnancy mouse models, maternal inflammation leads to subsequent GI injury in the mucosal and submucosal layers of the gut [ 146 ] and alteration of GI epithelial cells in the offspring, which play a key role in innate immunity [ 147 , 148 ]. In a human study of preterm infants, chorioamnionitis was shown to higher the incidence of late-onset sepsis and death among preterm infants and shifted the fecal microbiome of preterm infants [ 149 ].…”

The Link between Oral and Gut Microbiota in Inflammatory Bowel Disease and a Synopsis of Potential Salivary Biomarkers

“…This suggests there may be a relationship between improving the GI tract through beneficial commensal bacteria while simultaneously improving bacteria OTUs residing in the oral cavity [45]. While we cannot assume that saliva mirrors the human gut microbiome entirely, some studies suggest a shift in saliva microbial profiles may be reflective of a shift in gut microbiota profiles, especially with the supplementation of probiotics [46][47][48]. Studies show increased inflammatory responses due to oral cavity diseases that cause pernicious shifts in bacterial colony composition in both the oral cavity and the intestines.…”