Bombesin Preserves Goblet Cell Resistin‐Like Molecule β During Parenteral Nutrition but Not Other Goblet Cell Products

Abstract

Introduction Parenteral nutrition (PN) increases the risk of infection in critically ill patients and is associated with defects in gastrointestinal innate immunity. Goblet cells produce mucosal defense compounds including mucin (principally MUC2), trefoil factor 3 (TFF3,) and resistin-like molecule β (RELMβ). Bombesin (BBS), a gastin-releasing peptide analogue, experimentally reverses PN-induced defects in Paneth cell innate immunity. We hypothesized that PN reduces goblet cell product expression and PN+BBS would reverse these PN-induced defects. Methods 2 days after IV cannulation, male Institute of Cancer Research mice were randomized to Chow (n=15), PN (n=13), or PN+BBS (15 ug TID) (n=12) diets for 5 days. Defined segments of ileum and luminal fluid were analyzed for MUC2, TFF3, and RELMβ by qRT-PCR and Western blot. Th2 cytokines IL-4 and IL-13 were measured by ELISA. Results Compared to Chow, PN significantly reduced MUC2 in ileum (p<0.01), and luminal fluid (p=0.01). BBS supplementation did not improve ileal or luminal MUC2 compared to PN (p>0.3). Compared to Chow, PN significantly reduced TFF3 in ileum (p<0.02) and luminal fluid (p<0.01). BBS addition did not improve ileal or luminal TFF3 compared to PN (p>0.3). Compared to Chow, PN significantly reduced ileal RELMβ (p<0.01). BBS supplementation significantly increased ileal RELMβ to levels similar to Chow (p<0.03 vs. PN; p>0.6 vs. Chow). Th2 cytokines were decreased with PN and returned to Chow levels with BBS. Conclusion PN significantly impairs the goblet cell component of innate mucosal immunity. BBS only preserves goblet cell RELMβ during PN, but not other goblet cell products measured.

The Effect of Butyrate-Supplemented Parenteral Nutrition on Intestinal Defence Mechanisms and the Parenteral Nutrition-Induced Shift in the Gut Microbiota in the Rat Model

“…All of these factors prevent bacteria from coming into contact with the subepithelial layer and thus inducing the inflammatory response. PN administration disturbs these systems [ 6 , 7 , 10 , 30 – 33 ], resulting in the increased exposure of antigens to the immune system, increased intestinal permeability, and the establishment of proinflammatory status in the intestine.…”

The effect of butyrate-supplemented parenteral nutrition on intestinal defence mechanisms and the parenteral nutrition-induced shift in the gut microbiota

“…All of these factors prevent bacteria from coming into contact with the sub-epithelial layer and thus inducing the inflammatory response. PN administration disturbs these systems (6, 7, 10, 30-33), resulting in the increased exposure of antigens to the immune system, increased intestinal permeability, and the establishment of pro-inflammatory status in the intestine.…”

The Pathology and Physiology of Ileostomy

“…In patients who have undergone an ileostomy, the number of goblet cells in the distal intestinal mucosa is significantly reduced relative to the proximal intestinal mucosa (25), and our studies also showed that the mucus layer of the distal intestinal mucosa is significantly thinner than that of the proximal intestinal mucosa (Figure 2). In mice with PN, although no changes were observed in total goblet cell numbers when compared with normal mice, levels of MUC2, RELMβ, and TFF3 in the ileum and luminal fluid were reduced (26). Similar to goblet cells, Paneth cells are specialized secretory epithelial cells resident in the small intestinal crypts of Lieberkühn (27).…”