Preterm Birth and Necrotizing Enterocolitis Alter Gut Colonization in Pigs

Abstract

Necrotizing enterocolitis (NEC) in preterm neonates is dependent on bacterial colonization, but it remains unclear whether a particular microbiota or specific pathogens are involved. We hypothesized that gut colonization differs between preterm and term neonates and that overgrowth of Clostridium perfringens predisposes to NEC. By using terminal-RFLP and FISH, we characterized the gut microbiota of preterm, caesarean-delivered, formula-fed pigs (n ϭ 44) with or without NEC and of formula-or colostrum-fed term, and vaginally born pigs (n ϭ 13). A different microbiota with high C. perfringens abundance was observed in preterm pigs with NEC compared with healthy individuals. However, immunization against C. perfringens toxins did not prevent NEC, and C. perfringens inoculation (3.6 ϫ 10 8 cfu/d) failed to induce NEC (n ϭ 16), whereas prophylactic broad-spectrum antibiotics treatment prevented NEC (n ϭ 24). Colonization in both groups of term pigs differed from preterm pigs and was dominated by Lactobacilli spp. In conclusion, gestational age (GA) and NEC influence neonatal gut colonization, whereas diet has minor effects. C. perfringens is more abundant in pigs with NEC but rather as a consequence than a cause of disease. The general bacterial load and underdeveloped gut immune responses in preterm neonates seem more important for NEC development than specific pathogens. (Pediatr Res 69: 10-16, 2011)

Nutritional modulation of the gut microbiota and immune system in preterm neonates susceptible to necrotizing enterocolitis

“…Similar to the negative effects of delayed colonization, decreased bacterial diversity may also predispose the preterm gut to bacterial overgrowth by potentially pathogenic species (e.g., Klebsiella, Clostridium, Bacteriodes and Staphylococci species), which may contribute to diseases such as NEC [12,13,15,94]. We have confirmed in pigs that bacterial colonization differs markedly between preterm and term pigs reared in the same environment [95], supporting the notion that maturity of the intestine (preterm versus term) have marked effects on the first microbial community in the gut.…”

Early gradual feeding with bovine colostrum improves gut function and NEC resistance relative to infant formula in preterm pigs

“…Litter effects were a main determinant of the gut microbiome (litter-related genetics or environment), but the supplemental enteral diets also affected microbiota composition in the first week after birth. The microbiota changes are unlikely to be a direct cause of the early NEC lesions, firstly because the NEC lesions and gut structural and functional parameters did not show corresponding strong litter effects, secondly because the subtle changes induced by infant formula (e.g., less Clostridia) have previously been related to less NEC, not more NEC (14,58). Bacterial activity, virulence, quantity, and direct contact with the mucosa may be more important for mucosal dysfunction and NEC than the specific bacterial composition (14).…”

Physical Activity and Gastric Residuals as Biomarkers for Region-Specific NEC Lesions in Preterm Neonates

“…In some of our earlier studies, we classified NEC as a score of ≥3 in at least 1 region [12,15,16]. In this study, we also correlated physical activity with borderline NEC cases (very mild lesions; a score of 3; fig.…”