title: Carbohydrate maldigestion induces necrotizing enterocolitis in preterm pigs.
abstract: 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 immature carbohydrate digestive capacity. We tested the hypothesis that a formula containing maltodextrin vs. a formula containing lactose as the principal source of carbohydrate would predispose preterm pigs to a higher NEC incidence. Cesarean-derived preterm pigs were given total parenteral nutrition for 48 h followed by total enteral nutrition with a lactose-based (n = 11) or maltodextrin-based (n = 11) formula for 36 h. A higher incidence (91% vs. 27%) and severity (score of 3.3 vs. 1.8) of NEC were observed in the maltodextrin than in the lactose group. This higher incidence of NEC in the maltodextrin group was associated with significantly lower activities of lactase, maltase, and aminopeptidase; reduced villus height; transiently reduced in vivo aldohexose uptake; and reduced ex vivo aldohexose uptake capacity in the middle region of the small intestine. Bacterial diversity was low for both diets, but alterations in bacterial composition and luminal concentrations of short-chain fatty acids were observed in the maltodextrin group. In a second study, we quantified net portal absorption of aldohexoses (glucose and galactose) during acute jejunal infusion of a maltodextrin- or a lactose-based formula (n = 8) into preterm pigs. We found lower net portal aldohexose absorption (4% vs. 42%) and greater intestinal recovery of undigested carbohydrate (68% vs. 27%) in pigs acutely perfused with the maltodextrin-based formula than those perfused with the lactose-based formula. The higher digestibility of the lactose than the maltodextrin in the formulas can be attributed to a 5- to 20-fold higher hydrolytic activity of tissue-specific lactase than maltases. We conclude that carbohydrate maldigestion is sufficient to increase the incidence and severity of NEC in preterm pigs.
authors.affiliation: Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.forename: Hanne K
authors.initials: HK
authors.lastname: Møller
authors.forename: Barbara
authors.initials: B
authors.lastname: Stoll
authors.forename: Ann Cathrine F
authors.initials: AC
authors.lastname: Støy
authors.forename: Randal K
authors.initials: RK
authors.lastname: Buddington
authors.forename: Stine B
authors.initials: SB
authors.lastname: Bering
authors.forename: Bent B
authors.initials: BB
authors.lastname: Jensen
authors.forename: Oluyinka O
authors.initials: OO
authors.lastname: Olutoye
authors.forename: Richard H
authors.initials: RH
authors.lastname: Siggers
authors.forename: Lars
authors.initials: L
authors.lastname: Mølbak
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Burrin
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D002585:Cesarean Section; D004063:Digestion; D004195:Disease Models, Animal; D004750:Enteral Nutrition; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced / Q000201:enzymology / Q000382:microbiology / Q000503:physiopathology*; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D041943:Infant Formula / Q000008:administration & dosage; D007231:Infant, Newborn; D007408:Intestinal Absorption; D007422:Intestines / Q000201:enzymology / Q000254:growth & development / Q000382:microbiology / Q000503:physiopathology*; D043322:Lactase / Q000378:metabolism; D007785:Lactose / Q000008:administration & dosage; D010288:Parenteral Nutrition; D011134:Polysaccharides / Q000008:administration & dosage; D047928:Premature Birth; D012720:Severity of Illness Index; D013552:Swine; D013997:Time Factors; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D011134:Polysaccharides; C008315:maltodextrin; D043322:Lactase; D000520:alpha-Glucosidases; D000626:Aminopeptidases; D005947:Glucose; D007785:Lactose; D005690:Galactose