Preterm birth, bacterial colonization, and formula feeding predispose to
necrotizing enterocolitis (NEC).
Antibiotics are commonly administered to prevent
sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad-spectrum
antibiotic treatment improves NEC resistance and intestinal structure, function, and immunity in neonates. Caesarean-delivered preterm pigs were fed 3 days of
parenteral nutrition followed by 2 days of enteral formula. Immediately after birth, they were assigned to receive either
antibiotics (oral and parenteral doses of
gentamycin,
ampicillin, and
metronidazole, ANTI, n = 11) or saline in the control group (CON, n = 13), given twice daily. NEC lesions and intestinal structure, function, microbiology, and immunity markers were recorded. None of the ANTI but 85% of the CON pigs developed NEC lesions by day 5 (0/11 vs. 11/13, P < 0.05). ANTI pigs had higher intestinal villi (+60%), digestive
enzyme activities (+53-73%), and goblet cell densities (+110%) and lower
myeloperoxidase (-51%) and colonic microbial density (10(5) vs. 10(10) colony-forming units, all P < 0.05). Microarray transcriptomics showed strong downregulation of genes related to
inflammation and innate immune response to microbiota and marked upregulation of genes related to
amino acid metabolism, in particular
threonine,
glucose transport systems, and cell cycle in 5-day-old ANTI pigs. In a follow-up experiment, 5 days of
antibiotics prevented NEC at least until day 10. Neonatal prophylactic
antibiotics effectively reduced gut bacterial load, prevented NEC, intestinal
atrophy, dysfunction, and
inflammation and enhanced expression of genes related to gut metabolism and immunity in preterm pigs.