The effect of butyrate-supplemented total parenteral nutrition on muc2 mRNA and goblet cell chemotypes in a short bowel syndrome neonatal piglet model

摘要

Background: Compromised barrier function and bacterial translocation are common complications of short bowel syndrome (SBS) and parenteral nutrition (PN). Although mucins help prevent intestinal bacteria translocation, total mucin production has been shown to decrease during PN infusion. Butyrate administration may be a mucin fortifying strategy as it has been shown to increase mucin production in vivo and ex vivo. Objective: We tested the hypothesis that infusion of TPN supplemented with 9 mM butyrate will enhance protective goblet cell chemotypes in the small intestine, specifically sulfomucins, that enhancement of protective goblet cell chemotypes in the SCFA-supplemented group will be observed, since this group also contains 9 mM butyrate, that butyrate-supplemented TPN will have a greater effect on the small intestine than the large intestine, while butyrate supplementation at 60 mM will have a greater effect on the large intestine than the small intestine. We also hypothesize that muc2 mRNA abundance will increase in the small intestine with butyrate and SCFA-supplemented TPN infusion, whereas colonic muc2 mRNA abundance will increase in the colon with 60 mM butyrate administration.Methods: Forty-eight hour old piglets underwent 80% proximal jejunuoileal resection and were randomized to one of four groups: control total parenteral nutrition (TPN), TPN supplemented with 60 mM SCFA (36 mM acetate, 15 mM propionate, and 9 mM butyrate; SCFA), 9 mM butyrate (9Bu) or 60 mM butyrate (60Bu). Animals were further randomized to an acute (12 hour) or chronic (72 hour) time point. muc2 mRNA abundance, total goblet cell number, and total sulfomucin, sialomucin, acidomucin, and neutral mucin goblet cell numbers were ascertained.Results: Sulfomucin chemotypes were increased in the jejunal villi of the 9Bu group compared to control (treatment main effect, p=0.047). Acidomucin chemotypes in ileal crypts were greater in the 60Bu group than the control group (treatment main effect, p=0.038). In the colonic crypts, SCFA groups tended to have greater acidomucin chemotypes than control at 12h while 60Bu group tended to have greater acidomucin chemotypes per depth than control at 72h (p=0.060; Table 2.3). muc2 mRNA was increased in jejunal tissues in the 9Bu group compared to control with 270% and 30% increases in muc2 mRNA at 12 and 72 hours, respectively (p=0.010). Conclusion: The 9 mM Bu treatment increased protective goblet cell chemotypes and muc2 mRNA in the jejunum while 60 mM Bu increased protective goblet cell chemotypes in the ileum and colon. The 9Bu treatment was the most effective at upregulating muc2 mRNA abundance and sulfomucin chemotypes. Butyrate-supplemented PN may be a therapeutic strategy for bolstering the epithelial barrier by increasing mucin production in neonates with SBS on PN.