Bacteria and diet‐induced mucosal atrophy and dysfunction in small intestines of preterm pigs

Abstract

Preterm neonates fed milk formula commonly experience small intestinal (SI) mucosal atrophy and dysfunction, often increasing their susceptibility to intestinal diseases such as necrotizing enterocolitis (NEC). It is unknown if this negative intestinal response is exclusively diet-dependant or mediated by factors such as bacterial colonization. A preterm gnotobiotic pig model was used to determine if SI atrophy and dysfunction in the preterm intestine is bacterial dependant. Thirty-eight preterm pigs (93% gestation) were delivered via caesarean section and reared in either germ-free (GF) or conventional (CV) preterm isolators for 40–48 hours. Pigs were fed either infant milk formula (FORM) or sow’s colostrum (COL). Germ-free status was confirmed by aerobic and anaerobic cultivation. Pathological NEC lesions were present in some CV-FORM but absent in all GF-FORM and CV-COL pigs. Relative to CV-FORM, villus heights in the distal SI were increased 30% (P<0.01) in GF-FORM and CV-COL pigs. Relative dry mucosal weights were lowest in CV-FORM, and increased 11% (P<0.01) in GF-FORM and CV-COL pigs. Enzyme activities for aminopeptidases A and N were increased 20–23% (P<0.01) in GF-FORM and CV-COL pigs compared to CV-FORM pigs. Disaccharidase activities were less bacteria-dependant as indicated by the markedly lower (P<0.01) activities for maltase (70%) and lactase (38%) in FORM pigs compared to COL pigs. Similarly, maltase activities were increased in FORM pigs (39–44%, P<0.01) compared to COL pigs. In conclusion, the negative response to formula feeding in the SI of preterm neonates is not exclusively diet- induced, but in part mediated by bacterial colonization of the SI just after birth.