title: Early administration of probiotics alters bacterial colonization and limits diet-induced gut dysfunction and severity of necrotizing enterocolitis in preterm pigs.
abstract: Following preterm birth, bacterial colonization and enteral formula feeding predispose neonates to gut dysfunction and necrotizing enterocolitis (NEC), a serious gastrointestinal inflammatory disease. We hypothesized that administration of probiotics would beneficially influence early bacterial colonization, thereby reducing the susceptibility to formula-induced gut atrophy, dysfunction, and NEC. Caesarean-delivered preterm pigs were provided total parenteral nutrition (1.5 d) followed by enteral feeding (2 d) with porcine colostrum (COLOS; n = 5), formula (FORM; n = 9), or formula with probiotics (FORM-P; Bifidobacterium animalis and Lactobacillus: L. acidophilus, L. casei, L. pentosus, L. plantarum; n = 13). Clinical NEC scores were reduced (P < 0.05) in FORM-P (2.0 +/- 0.2) and COLOS groups (1.7 +/- 0.5) compared with FORM pigs (3.4 +/- 0.6). Lower NEC scores were associated with elevated intestinal weight, mucosa proportion, villus height, RNA integrity, and brush border aminopeptidase A and N activities, and lower gastric organic acid concentration in the FORM-P and COLOS groups (P < 0.05). Diversity of the mucosa-associated bacteria in the distal small intestine was similar among formula-fed pigs, yet the abundance of specific bacterial groups differed between FORM-P and FORM pigs. FORM-P pigs had lower colonization density of a potential pathogen, Clostridium perfringens, and had commensal Lactobacillus bacteria more closely associated with enterocytes along the villus-crypt axis relative to FORM pigs. These results suggest that probiotic administration immediately after birth promotes the colonization of a beneficial commensal microbiota capable of limiting the formula-induced mucosal atrophy, dysfunction, and pathogen load in preterm neonates, thereby reducing the incidence and severity of NEC.
authors.affiliation: Department of Human Nutrition, University of Copenhagen, DK-1958 Frederiksberg, Denmark.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Siggers
authors.forename: Jayda
authors.initials: J
authors.lastname: Siggers
authors.forename: Mette
authors.initials: M
authors.lastname: Boye
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.forename: Lars
authors.initials: L
authors.lastname: Mølbak
authors.forename: Thomas
authors.initials: T
authors.lastname: Leser
authors.forename: Bent B
authors.initials: BB
authors.lastname: Jensen
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001644:Bifidobacterium / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy / Q000517:prevention & control*; D005260:Female; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000517:prevention & control*; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000382:microbiology*; D007778:Lactobacillus / Q000502:physiology; D008297:Male; D011247:Pregnancy; D047928:Premature Birth; D019936:Probiotics / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D013552:Swine
chemical_list: D016207:Cytokines