TY - JOUR

T1 - Neonatal gut and immune maturation is determined more by postnatal age than by postconceptional age in moderately preterm pigs

AU - Ren, Shuqiang

AU - Hui, Yan

AU - Obelitz-Ryom, Karina

AU - Brandt, Anne Bladt

AU - Kot, Witold

AU - Nielsen, Dennis Sandris

AU - Thymann, Thomas

AU - Sangild, Per Torp

AU - Nguyen, Duc Ninh

PY - 2018

Y1 - 2018

N2 - Preterm infants have immature organ functions that predispose them to gut and immune disorders. Developmental delays at preterm birth may affect various organs differently at term-corrected age. We hypothesized that gut and immune maturation in moderately preterm neonates depends more on birth and postnatal factors than on advancing post-conceptional age (PCA). Using preterm pigs as models, we investigated how gut and immune parameters develop until term-corrected age, and how these differ from those in term counterparts. Preterm (n=43, 106 d of gestation) and term pigs (n=41, 116 d of gestation) were delivered by caesarean section, and euthanized at birth (d 1) or postnatal d 11 (term-corrected age for preterm pigs), using identical rearing conditions. Relative to term pigs, preterm pigs had lower blood oxygenation, glucose, and cortisol levels, lower gut lactase activity, villus height and goblet cell density, and lower blood neutrophil, helper-T and cytotoxic-T cell numbers at birth. Despite slower growth in preterm pigs, most intestinal and immune parameters increased markedly after birth in both groups. However, some parameters remained negatively affected by preterm birth until postnatal d 11 (goblet cells, gut permeability, cytotoxic-T cells). The colon microbiota showed limited differences between preterm and term pigs at this time. At the same PCA, preterm 11 d-old pigs had higher blood leukocyte numbers and gut enzyme activities but lower villus height and blood cytotoxic-T cell numbers, relative to newborn term pigs. Birth and postnatal factors, not advancing PCA, are key determinants of gut and immune maturation in moderately preterm neonates.

AB - Preterm infants have immature organ functions that predispose them to gut and immune disorders. Developmental delays at preterm birth may affect various organs differently at term-corrected age. We hypothesized that gut and immune maturation in moderately preterm neonates depends more on birth and postnatal factors than on advancing post-conceptional age (PCA). Using preterm pigs as models, we investigated how gut and immune parameters develop until term-corrected age, and how these differ from those in term counterparts. Preterm (n=43, 106 d of gestation) and term pigs (n=41, 116 d of gestation) were delivered by caesarean section, and euthanized at birth (d 1) or postnatal d 11 (term-corrected age for preterm pigs), using identical rearing conditions. Relative to term pigs, preterm pigs had lower blood oxygenation, glucose, and cortisol levels, lower gut lactase activity, villus height and goblet cell density, and lower blood neutrophil, helper-T and cytotoxic-T cell numbers at birth. Despite slower growth in preterm pigs, most intestinal and immune parameters increased markedly after birth in both groups. However, some parameters remained negatively affected by preterm birth until postnatal d 11 (goblet cells, gut permeability, cytotoxic-T cells). The colon microbiota showed limited differences between preterm and term pigs at this time. At the same PCA, preterm 11 d-old pigs had higher blood leukocyte numbers and gut enzyme activities but lower villus height and blood cytotoxic-T cell numbers, relative to newborn term pigs. Birth and postnatal factors, not advancing PCA, are key determinants of gut and immune maturation in moderately preterm neonates.

U2 - 10.1152/ajpgi.00169.2018

DO - 10.1152/ajpgi.00169.2018

M3 - Journal article

C2 - 30118350

VL - 315

SP - G855-G867

JO - American Journal of Physiology: Gastrointestinal and Liver Physiology

JF - American Journal of Physiology: Gastrointestinal and Liver Physiology

SN - 0193-1857

IS - 5

ER -