title: Human milk oligosaccharide effects on intestinal function and inflammation after preterm birth in pigs.
abstract: Human milk oligosaccharides (HMOs) may mediate prebiotic and anti-inflammatory effects in newborns. This is particularly important for preterm infants who are highly susceptible to intestinal dysfunction and necrotizing enterocolitis (NEC). We hypothesized that HMO supplementation of infant formula (IF) improves intestinal function, bacterial colonization and NEC resistance immediately after preterm birth, as tested in a preterm pig model. Mixtures of HMOs were investigated in intestinal epithelial cells and in preterm pigs (n=112) fed IF supplemented without (CON) or with a mixture of four HMOs (4-HMO) or >25 HMOs (25-HMO, 5-10 g/L given for 5 or 11 days). The 25-HMO blend decreased cell proliferation and both HMO blends decreased lipopolysaccharide-induced interleukin-8 secretion in IPEC-J2 cells, relative to control (P<.05). All HMOs were found in urine and feces of HMO-treated pigs, and short-chain fatty acids in the colon were higher in HMO vs. CON pigs (P<.05). After 5 days, NEC lesions were similar between HMO and CON pigs and 25-HMO increased colon weights (P<.01). After 11 days, the 4-HMO diet did not affect NEC (56 vs. 79%, P=.2) but increased dehydration and diarrhea (P<.05) and expression of immune-related genes (IL10, IL12, TGFβ, TLR4; P<.05). Bacterial adherence and diversity was unchanged after HMO supplementation.
  
  
  
  Complex HMO-blends affect intestinal epithelial cells in vitro and gut gene expression and fermentation in preterm pigs. However, the HMOs had limited effects on NEC and diarrhea when supplemented to IF. Longer-term exposure to HMOs may be required to improve the immature intestinal function in formula-fed preterm neonates.
authors.affiliation: Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 68, 1870 Frederiksberg C, Denmark; Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark.
authors.forename: Stine O
authors.initials: SO
authors.lastname: Rasmussen
authors.affiliation: Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 68, 1870 Frederiksberg C, Denmark; Institute of Animal Nutrition, Department of Veterinary Medicine, Free University Berlin, Königin-Luise-Str. 49, 14195 Berlin, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Martin
authors.affiliation: Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 68, 1870 Frederiksberg C, Denmark; Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark.
authors.forename: Mette V
authors.initials: MV
authors.lastname: Østergaard
authors.affiliation: Institute of Nutritional Science, Justus-Liebig-University Giessen, Ludwigstraße 23, 35390 Giessen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rudloff
authors.affiliation: Section of Microbiology, Dept. of Biology, University of Copenhagen, Universitetsparken 15, 2100 Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Roggenbuck
authors.affiliation: Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 68, 1870 Frederiksberg C, Denmark; Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark.
authors.forename: Duc Ninh
authors.initials: DN
authors.lastname: Nguyen
authors.affiliation: Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 68, 1870 Frederiksberg C, Denmark; Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark.
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
authors.affiliation: Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 68, 1870 Frederiksberg C, Denmark; Department of Nutrition, Exercise, and Sports, Faculty of Science, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark. Electronic address: sbb@sund.ku.dk.
authors.forename: Stine B
authors.initials: SB
authors.lastname: Bering
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D006801:Humans; D041943:Infant Formula; D007249:Inflammation / Q000517:prevention & control; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008895:Milk, Human / Q000737:chemistry*; D009844:Oligosaccharides / Q000494:pharmacology*; D009929:Organ Size; D011247:Pregnancy; D047928:Premature Birth; D034421:Sus scrofa
chemical_list: D016207:Cytokines; D009844:Oligosaccharides
keywords: Gastrointestinal development; Gut health; Human milk oligosaccharides; Necrotizing enterocolitis; Preterm pigs