title: Sialylated galacto-oligosaccharides and 2'-fucosyllactose reduce necrotising enterocolitis in neonatal rats.
abstract: Necrotising enterocolitis (NEC) is one of the most frequent and fatal intestinal disorders in preterm infants and has very limited treatment options. Breast-fed infants are at a 6-10-fold lower NEC risk than formula-fed infants, and we have previously shown that human milk oligosaccharides (HMO) improved survival and reduced pathology in a rat NEC model. The HMO disialyllacto-N-tetraose (DSLNT) was most effective, and sialylation was shown to be essential for its protective effect. Galacto-oligosaccharides (GOS), currently added to some infant formula, but not containing sialic acid, had no effect. In addition to DSLNT, our previous work also showed that the neutral HMO fraction, which contains high concentrations of 2'-fucosyllactose (2'FL), slightly improved pathology scores. Here, we assessed the in vivo efficacy of 2'FL, as well as of GOS that we enzymatically sialylated (Sia-GOS). Neonatal rats were randomised into the following study groups - dam-fed (DF), formula-fed (FF), FF containing pooled HMO (10 mg/ml), GOS (8 mg/ml), Sia-GOS (500 µm) or 2'FL (2 mg/ml) - and subjected to the established NEC protocol. The DF and HMO groups had the lowest pathology scores with mean values of 0·67 (sd 0·34) and 0·90 (sd 0·47), respectively. The FF group had significantly elevated pathology scores of 2·02 (sd 0·63). Although the addition of GOS to the formula had no protective effect and generated scores of 2·00 (sd 0·63), the addition of Sia-GOS or 2'FL significantly lowered pathology scores to 1·32 (sd 0·56) (P<0·0034) and 1·43 (sd 0·51) (P<0·0040), respectively. The results warrant further studies to investigate the underlying mechanisms and to assess safety and efficacy in human neonates.
authors.affiliation: 1Division of Neonatology and Division of Gastroenterology,Hepatology and Nutrition,Department of Pediatrics,University of California,San Diego,La Jolla, CA 92093,USA.
authors.forename: Chloe A
authors.initials: CA
authors.lastname: Autran
authors.affiliation: 2FrieslandCampina,3818 LE Amersfoort,The Netherlands.
authors.forename: Margriet H C
authors.initials: MH
authors.lastname: Schoterman
authors.affiliation: 1Division of Neonatology and Division of Gastroenterology,Hepatology and Nutrition,Department of Pediatrics,University of California,San Diego,La Jolla, CA 92093,USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Jantscher-Krenn
authors.affiliation: 3Microbial Physiology,Groningen Biomolecular Sciences and Biotechnology Institute,University of Groningen,9747 AG Groningen,The Netherlands.
authors.forename: Johannis P
authors.initials: JP
authors.lastname: Kamerling
authors.affiliation: 1Division of Neonatology and Division of Gastroenterology,Hepatology and Nutrition,Department of Pediatrics,University of California,San Diego,La Jolla, CA 92093,USA.
authors.forename: Lars
authors.initials: L
authors.lastname: Bode
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001942:Breast Feeding; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy*; D005260:Female; D005690:Galactose / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D041943:Infant Formula / Q000737:chemistry*; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012794:Sialic Acids / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D014312:Trisaccharides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D009844:Oligosaccharides; D012794:Sialic Acids; D014312:Trisaccharides; C576246:disialyllacto-N-tetraose; D005690:Galactose; C031420:2'-fucosyllactose
keywords: 2′-Fucosyllactose; 2′FL 2′-fucosyllactose; DF dam-fed; DP degree of polymerisation; DSLNT disialyllacto--tetraose; FF formula-fed; GOS galacto-oligosaccharides; Galacto-oligosaccharides; HMO human milk oligosaccharides; Human milk oligosaccharides; Infant formula; NEC necrotising enterocolitis; Necrotising enterocolitis; Premature infants; Sia-GOS sialylated galacto-oligosaccharides