Diet-dependent mucosal colonization and interleukin-1beta responses in preterm pigs susceptible to necrotizing enterocolitis.
OBJECTIVE
Intestinal colonization challenges the neonatal innate immune system, especially in newborns with an immature immune response lacking the supportive bioactive components from mother's milk. Accordingly, formula-fed preterm pigs frequently show bacterial overgrowth, mucosal atrophy, and gut lesions reflecting necrotizing enterocolitis (NEC) within the first days after birth. We hypothesized that NEC development is related to a diet-dependent bacterial adherence and a subsequent proinflammatory cytokine response in the gut mucosa immediately after introduction of enteral food.


METHODS
Premature piglets (92% gestation) received 2 to 3 days of total parenteral nutrition followed by 0, 8, or 17 hours of enteral formula or sow's colostrum feeding.


RESULTS
Following 8 hours, but not 17 hours, of colostrum feeding, a reduced number of intestinal samples with adherent bacteria (both Gram-negative and Gram-positive bacteria) was counted compared with 0 or 8 hours of formula feeding. Besides a more dense colonization, formula feeding leads to higher intestinal interleukin-1beta (IL-1beta) levels and more NEC-like lesions from 8 hours onward. The load of adherent bacteria was especially high in NEC lesions. Toll-like receptor 4 was detected in enteroendocrine, neuronal, and smooth muscle cells, potentially mediating the increase in IL-1beta levels by Gram-negative bacteria.


CONCLUSIONS
Formula feeding facilitates bacterial adherence and the development of a proinflammatory state of the intestine, which may be among the key factors that predispose formula-fed preterm neonates to NEC.
Van Haver
Els R
ER
Department of Veterinary Medicine, University of Antwerp, Wilrijk, Belgium.
Sangild
Per T
PT
Oste
Marijke
M
Siggers
Jayda L A
JL
Weyns
Andre L M
AL
Van Ginneken
Christa J
CJ
D000818:Animals; D000831:Animals, Newborn; D001422:Bacterial Adhesion; D015169:Colony Count, Microbial; D003126:Colostrum / Q000276:immunology*; D004032:Diet; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D053583:Interleukin-1beta / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D008070:Lipopolysaccharides; D010288:Parenteral Nutrition; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4