title: The incidence of necrotizing enterocolitis is increased following probiotic administration to preterm pigs.
abstract: Preterm birth and necrotizing enterocolitis (NEC) is associated with inappropriate gut colonization and immunity, which may be improved by probiotic bacteria. Using a preterm pig model of NEC, we investigated the effects of probiotics on intestinal structure, function, microbiology, and immunology in the immediate postnatal period. Just after birth, caesarean-delivered preterm pigs were inoculated with Lactobacillus paracasei, Bifidobacteria animalis, and Streptococcus thermophilus (total 2.4 × 10(10)/d) either as live (ProLive, n = 14) or gamma-irradiated dead bacteria (ProDead, n = 12) and compared with controls (n = 14). All pigs received parenteral nutrition for 2 d followed by enteral formula feeding until tissue collection on d 5. Compared with control pigs, intestinal weight was lower and NEC incidence was higher in both groups given probiotics (64-67 vs. 14%; P<0.01). Hexose absorption, brush border enzyme activities, and gut barrier function were lower in the ProDead group compared with the other groups (P < 0.05), whereas live probiotics induced higher expression of the proinflammatory cytokines IL-1α and IL-6 (P < 0.05). Probiotics minimally affected gut colonization, except that live probiotics induced a higher density of B. animalis and lower bacterial diversity in the distal intestinal mucosa and lower SCFA concentrations in the colon (P < 0.05). The detrimental effects of probiotic bacteria in this study may relate to the specific strain and dose combination and may have involved the very immature gut immune system and low NEC incidence in the control group. It remains to be determined whether similar adverse responses to probiotics occur in preterm infants.
authors.affiliation: Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Malene S
authors.initials: MS
authors.lastname: Cilieborg
authors.forename: Thomas
authors.initials: T
authors.lastname: Thymann
authors.forename: Richard
authors.initials: R
authors.lastname: Siggers
authors.forename: Mette
authors.initials: M
authors.lastname: Boye
authors.forename: Stine B
authors.initials: SB
authors.lastname: Bering
authors.forename: Bent B
authors.initials: BB
authors.lastname: Jensen
authors.forename: Per T
authors.initials: PT
authors.lastname: Sangild
mesh_terms: D000818:Animals; D001644:Bifidobacterium; D003106:Colon / Q000382:microbiology*; D020345:Enterocolitis, Necrotizing / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D015994:Incidence; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D007778:Lactobacillus; D023421:Models, Animal; D018529:Nutritional Support; D009929:Organ Size; D019936:Probiotics / Q000009:adverse effects*; D048249:Streptococcus thermophilus; D013552:Swine