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© 2008 American Society for Nutrition J. Nutr. 138:1437-1444, August 2008


Nutrition and Disease

Early Administration of Probiotics Alters Bacterial Colonization and Limits Diet-Induced Gut Dysfunction and Severity of Necrotizing Enterocolitis in Preterm Pigs1–3,

Richard H. Siggers4, Jayda Siggers4, Mette Boye5, Thomas Thymann4, Lars Mølbak5, Thomas Leser6, Bent B. Jensen7 and Per T. Sangild4,*

4 Department of Human Nutrition, University of Copenhagen, DK-1958 Frederiksberg, Denmark; 5 National Veterinary Institute, Technical University of Denmark, DK-1790 Copenhagen, Denmark; 6 Corporate Research, Chr. Hansen, A/S, Bøge Allé 10-12, DK-2970 Hørsholm; and 7 Faculty of Agricultural Sciences, Aarhus University, DK-8830 Tjele, Denmark

* To whom correspondence should be addressed. E-mail: psa{at}life.ku.dk.

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.





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