Starvation Compromises Paneth Cells

Abstract

The intestine is challenged with the task of protecting the body's internal milieu against bacterial invasion. To this end, the gut is equipped with an epithelial lining connected by tight junctions, a mucus layer, gut-associated lymphoid tissue, and Paneth cells. Paneth cells are highly specialized epithelial cells located in the crypts of the small intestine, and play an important role in gut innate immunity. 1 These cells sense bacterial presence and secrete granules containing antimicrobial peptides, including lysozyme, RegIII␥, and cryptdins (the murine counterparts of human ␣-defensins) both constitutively and in response to activation by bacteria or their products. 2 Using a murine cell ablation model, Paneth cells were shown to be crucial in host protection against invasion of both commensal and pathogenic microbiota. 3 In addition, our group has recently shown the additive importance of Paneth cells in preventing bacterial translocation in situations of physical intestinal barrier loss. 4 Enteral starvation and total parenteral nutrition, as applied to critically ill patients, are reported to result in increased gut wall permeability, a compromised immune system, and bacterial translocation. 5-10 Because autophagy, a process induced on starvation, 11-13 influences the generation of Paneth cell granules, 14 we hypothesize that enteral starvation impairs Paneth cell function, contributing to starvation-associated gut compromise.In this study, the effects of food deprivation on Paneth cell function were investigated using a mouse starvation model. We provide evidence that lack of enteral feeding results in Paneth cell autophagy, decreased expression of antimicrobial products (ie, lysozyme, cryptdin, and RegIII␥), and the presence of atypical secretory granules. Our results propose compromised Paneth cells to be involved in the reduced protection against bacterial translocation in enteral starvation.

Alterations of gut barrier and gut microbiota in food restriction, food deprivation and protein-energy wasting

“…In animals, calorie deprivation and restriction increase small bowel permeability determined by the FITC-dextran fluxes [20], and increase whole bowel intestinal permeability assessed by serum levels of ovalbumin [16]. Similarly, the progression to cachexia, an advanced state of PEW, in a mouse model of cancer, was related to increased whole gut permeability to FITC-dextran [39].…”

The Enteric Nervous System Neuropeptide, Bombesin, Reverses Innate Immune Impairments During Parenteral Nutrition

“…Starvation itself decreases the number of Paneth cell granules and distorts granule packaging and exocytosis, also reducing production of constitutively produced AMPs. 40 These effects are likely related to the lack of enteral stimulation rather than malnutrition since PN prevents malnutrition while the results of starvation and lack of enteral feeding on Paneth cells appear similar. Our results show that PN with lack of enteral stimulation decreases AMP transcription and production which is evident in the alterations in mRNA, immunohistochemistry, and tissue levels.…”

“…mRNA data is consistent with results from Hodin et al who found decreased production of constitutively expressed AMPs, including cryptdins, in a starvation model. 40 A better method for cryptdin protein detection is necessary to further research its mechanism of production and secretion from Paneth cells.…”

Defensins in Enteric Mucosal Immunity

“…Paneth cell homeostasis is essential to small intestinal health and integrity (Clevers and Bevins, 2013;Hodin et al, 2011a;Grootjans et al, 2011). Because Paneth cells are the only source of α-defensins in the small intestine, the availability and mucosal impact of enteric α-defensins are linked inextricably to Paneth cell biology and homeostasis.…”