Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs

Authors: PUIMAN, PATRYCJA - Erasmus Medical Center; JENSEN, MIKKEL - University Of Copenhagen; STOLL, BARBARA - Children'S Nutrition Research Center (CNRC); RENES, INGRID - Erasmus Medical Center; DE BRUIJN, ADRIANUS - Erasmus Medical Center; DORST, KRISTIEN - Erasmus Medical Center; SCHIERBEEK, HENK - Erasmus Medical Center; SCHMIDT, METTE - University Of Copenhagen; BOEHM, GUNTHER - Erasmus Medical Center; Burrin, Douglas - Doug; SANGILD, PER - University Of Copenhagen; VAN GOUDOEVER, JOHANNES - Erasmus Medical Center

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/18/2011
Publication Date: 5/18/2011
Citation: Puiman, P.J., Jensen, M., Stoll, B., Renes, I.B., De Bruijn, A.C., Dorst, K., Schierbeek, H., Schmidt, M., Boehm, G., Burrin, D.G., Sangild, P.T., Goudoever, J.B. 2011. Intestinal threonine utilization for protein and mucin synthesis is decreased in formula-fed preterm pigs. Journal of Nutrition. 141(7):1306-1311.

Interpretive Summary: Necrotizing enterocolitis (NEC) remains the most severe gastrointestinal disorder in preterm infants. It is associated with the initiation of enteral nutrition and may be related to immaturity in the gut barrier function. Threonine is an amino acid required in the diet of infants and is used to make a key gut immune protein present in mucus, called mucin 2 (MUC2). We previously showed premature piglets fed formula have increased risk for NEC compared to colostrum or breast-fed pigs. Thus, we tested whether premature piglets fed formula have abnormal MUC2 production and threonine uptake by the gut compared to colostrum fed pigs. We found that formula-fed pigs has lower gut threonine uptake and lower synthesis of total protein and specifically, MUC2. The results suggest that formula-feeding leads to abnormally low availability of threonine and MUC2 production, which contributes to the poor intestinal barrier function and increased risk for NEC. These results further support continued recommendations to feed premature infants human breast milk to prevent NEC.

Technical Abstract: Threonine is an essential amino acid necessary for synthesis of intestinal (glyco)proteins such as mucin (MUC2) to maintain adequate gut barrier function. In premature infants, reduced barrier function may contribute to the development of necrotizing enterocolitis (NEC). Human milk protects against NEC compared with infant formula. Therefore, we hypothesized that formula feeding decreases the MUC2 synthesis rate concomitant with a decrease in intestinal first-pass threonine utilization, predisposing the preterm neonate to NEC. Preterm pigs were delivered by caesarian section and received enteral feeding with formula (FORM; "n" = 13) or bovine colostrum (COL; "n" = 6) for 2 d following 48 h of total parenteral nutrition. Pigs received a dual stable isotope tracer infusion of threonine to determine intestinal threonine kinetics. NEC developed in 38 percent of the FORM pigs, whereas none of the COL pigs were affected ("P" = 0.13). Intestinal fractional first-pass threonine utilization was lower in FORM pigs (49 +/- 2 percent) than in COL pigs (60 +/- 4 percent) ("P" = 0.02). In FORM pigs compared with COL pigs, protein synthesis (369 +/- 31 mg/kg(-1)per d(-1) vs. 615 +/- 54 mg/kg(-1)per d(-1); "P" = 0.003) and MUC2 synthesis (121 +/- 17 percent/d vs. 184 +/- 15 percent/d; "P" = 0.02) were lower in the distal small intestine (SI). Our results suggest that formula feeding compared with colostrum feeding in preterm piglets reduces mucosal growth with a concomitant decrease in first-pass splanchnic threonine utilization, protein synthesis, and MUC2 synthesis in the distal SI. Hence, decreased intestinal threonine metabolism and subsequently impaired gut barrier function may predispose the formula-fed infant to developing NEC.