Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs

Abstract

Preterm infants often tolerate full enteral nutrition a few weeks after birth but it is not known how this is related to gut maturation. Using pigs as models, we hypothesized that intestinal structure and digestive function are similar in preterm and term individuals at 3-4 wk after birth and that early enteral nutrition promotes maturation. Preterm or term cesareandelivered pigs were fed total parenteral nutrition, or partial enteral nutrition [Enteral (Ent), 16 -64 ml·kg Ϫ1 ·day Ϫ1 of bovine colostrum] for 5 days, followed by full enteral milk feeding until day 26. The intestine was collected for histological and biochemical analyses at days 0, 5, and 26 (n ϭ 8 -12 in each of 10 treatment groups). Intestinal weight (relative to body weight) was reduced in preterm pigs at 0 -5 days but ENT feeding stimulated the mucosal volume and peptidase activities. Relative to term pigs, mucosal volume remained reduced in preterm pigs until 26 days although plasma glucagon-like peptide 2 (GLP-2) and glucose-dependent insulin-trophic peptide (GIP) levels were increased. Preterm pigs also showed reduced hexose absorptive capacity and brush-border enzyme (sucrase, maltase) activities at 26 days, relative to term pigs. Intestinal structure shows a remarkable growth adaptation in the first week after preterm birth, especially with enteral nutrition, whereas some digestive functions remain immature until at least 3-4 wk. It is important to identify feeding regimens that stimulate intestinal maturation in the postnatal period of preterm infants because some intestinal functions may show long-term developmental delay. prematurity; gut development; enzymes; digestion; glucagon-like peptide 2 ABOUT 10% OF ALL INFANTS are born preterm (Ͻ37 weeks of gestation) and the proportion is increasing in most countries (6). Preterm infants show an increased susceptibility to infections, respiratory distress syndrome, intracranial hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity, extrauterine growth restriction, neurodevelopmental disturbances, and necrotizing enterocolitis (NEC) (21, 31). The challenges are inversely related to gestational age at birth and the most severe adaptation problems occur during the first few weeks after birth. If preterm infants survive the difficult neonatal period, their body functions often adapt well, although some organ systems may show long-term developmental delay or deficits (18). It remains unknown how different organ systems adapt in preterm infants and when parameters of structure and function become similar to those in term infants. For gastrointestinal (GI) functions, eating disorders and dysregulated appetite have been reported in preterm infants (44) but very little is known about the long-term adaptation of the GI tract in preterm neonates.Investigations of postnatal GI adaptation in preterm neonates are difficult without an animal model that combines preterm birth, high NEC risk, and clinically relevant feeding interventions, such as parenteral and enteral nutrition. Piglets delivere...

Limited effects of preterm birth and the first enteral nutrition on cerebellum morphology and gene expression in piglets

“…These environmental triggers have short‐ or long‐term effects on the developing gut depending on each specific structure or function (Hansen et al. ). Perhaps the brain is better protected by the meninges and the blood–brain barrier, and postnatal triggers are therefore less likely to have an immediate and strong effect on CNS development, beyond the genetic developmental program mainly determined by the PCA.…”

“…In contrast to the brain, maturation of the gut is always affected immediately after birth, preterm or term, partly mediated by the exposure to nutritional and microbiota triggers (Sangild et al 2013). These environmental triggers have short-or long-term effects on the developing gut depending on each specific structure or function (Hansen et al 2016). Perhaps the brain is better protected by the meninges and the blood-brain barrier, and postnatal triggers are therefore less likely to have an immediate and strong effect on CNS development, beyond the genetic developmental program mainly determined by the PCA.…”

“…Hif-1a (P1) our study. In the postnatal period, we chose to collect brains on day 5 for both groups because here preterm pigs become fully mobile, have a stable metabolism and respiration and show marked gut maturational responses to enteral feeding (Sangild et al 2013;Cao et al 2015;Andersen et al 2016;Hansen et al 2016). The fact that cerebellar white matter grows faster than gray matter in the perinatal period of preterm pigs suggests that processes involving myelination or glial cell neurogenesis is important in the preterm cerebellum during the first postnatal month.…”

Delayed development of systemic immunity in preterm pigs as a model for preterm infants

“…During the first 4 weeks of life, preterm pigs suffered more from diarrhea and poor weight gain than piglets delivered close to term, possibly reflecting their immature digestive capacity but potentially also metabolic and immunological deficits2233. Regardless, there were no clinical signs of NEC (e.g.…”

Neonatal gut and immune maturation is determined more by postnatal age than by postconceptional age in moderately preterm pigs

“…During early life, the postnatal immune system normally undergoes a gradual transition from a Th2-skewed immunity in the maternal-fetal condition to a more predominant Th1 immunity pattern following exposure to foreign antigens (4). At the same PNA, preterm and term infants and animals appear to differ in their gut functions, immune responses, and susceptibility to neonatal diseases (16,36,41). Together, this suggests that preterm neonates may undergo a unique pattern of gut and immune maturation when they, ahead of time, have to adapt to an abrupt transition from a protected in utero environment to an ex utero environment with independent respiration, enteral feeding, and exposure to foreign antigens after preterm birth.…”