Nutrient restriction has limited short-term effects on gut, immunity, and brain development in preterm pigs

Authors: AHNFELDT, AGNETHE - University Of Copenhagen; BAEK, OLE - University Of Copenhagen; HUI, YAN - University Of Copenhagen; NIELSEN, CHARLOTTE - University Of Copenhagen; OBELITZ-RYOM, KARINA - University Of Copenhagen; BUSK-ANDERSON, TILLA - University Of Copenhagen; RUGE, ANNE - University Of Copenhagen; HOLST, JENS - University Of Copenhagen; RUDLOFF, SILVIA - Justus-Liebig University; Burrin, Douglas - Doug; NGUYEN, DUC - University Of Copenhagen; NIELSEN, DENNIS - University Of Copenhagen; ZACHARIASSEN, GITTE - Odense University Hospital; BERING, STINE - University Of Copenhagen; THYMANN, THOMAS - University Of Copenhagen; SANGILD, PER - University Of Copenhagen

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/30/2020
Publication Date: 2/18/2020
Citation: Ahnfeldt, A., Baek, O., Hui, Y., Nielsen, C., Obelitz-Ryom, K., Busk-Anderson, T., Ruge, A., Holst, J., Rudloff, S., Burrin, D.G., Nguyen, D., Nielsen, D., Zachariassen, G., Bering, S., Thymann, T., Sangild, P. 2020. Nutrient restriction has limited short-term effects on gut, immunity, and brain development in preterm pigs. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa030.
DOI: https://doi.org/10.1093/jn/nxaa030

Interpretive Summary: Premature birth is a worldwide problem and leads to growth failure and neurodevelopmental delay in children. The underlying reason for poor growth in premature infants is poorly understood. This is because providing the optimum level of nutrition is often not possible for these infants, because they cannot tolerate full feeding due to underlying disease conditions. In this study we tested if providing a suboptimal level of nutrition that restricts body growth was sufficient to maintain normal organ maturation and function using the preterm pig as a model for human preterm infants. Newborn preterm pigs were randomized to be fed diluted bovine colostrum or colostrum-fortified diluted bovine milk for 19 days. The study found as predicted that lower nutrient intake reduced overall body growth. However, most of the measurements of organ growth and functions of the gut, brain and immune system were normal in pigs despite being fed a lower level of nutrition. The results show the resilience of the premature newborn to adapt to suboptimal nutrition and still main essential body functions.

Technical Abstract: Extrauterine growth restriction (EUGR) in preterm infants is associated with higher morbidity and impaired neurodevelopment. Early nutrition support may prevent EUGR in preterm infants, but it is not known if this improves organ development and brain function in the short and long term. Using pigs as models for infants, we hypothesized that diet-induced EUGR impairs gut, immunity, and brain development in preterm neonates during the first weeks after birth. Forty-four preterm caesarean-delivered pigs (Danish Landrace x Large White x Duroc, birth weight 975 +/-235 g, male:female ratio 23:21) from 2 sows were fed increasing volumes [32-180 mL/(kg/d)] of dilute bovine milk (EUGR group) or the same diet fortified with powdered bovine colostrum for 19 d (CONT group, 50-100% higher protein and energy intake than the EUGR group). The EUGR pigs showed reduced body growth (-39%, P < 0.01), lower plasma albumin, phosphate, and creatine kinase concentrations (-35 to 14%, P < 0.05), increased cortisol and free iron concentrations (+130 to 700%, P < 0.05), and reduced relative weights of the intestine, liver, and spleen (-38 to 19%, all P < 0.05). The effects of EUGR on gut structure, function, microbiota, and systemic immunity were marginal, although EUGR temporarily increased type 1 helper T cell (Th1) activity (e.g. more blood T cells and higher Th1-related cytokine concentrations on day 8) and reduced colon nutrient fermentation (lower SCFA concentration; -45%, P < 0.01). Further, EUGR pigs showed increased relative brain weights (+19%, P < 0.01), however, memory and learning, as tested in a spatial T-maze, were not affected. Most of the measured organ growth, and digestive, immune, and brain functions showed limited effects of diet-induced EUGR in preterm pigs during the first weeks after birth. Likewise, preterm infants may show remarkable physiological adaptation to deficient nutrient supply during the first weeks of life although early life malnutrition may exert negative consequences later.