Gut and immune effects of bioactive milk factors in preterm pigs exposed to prenatal inflammation

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Shuqiang Ren, Yan Hui, Sandra Goericke-Pesch, Stanislava Pankratova, Witold Kot, Xiaoyu Pan, Thomas Thymann, Per T Sangild, Duc Ninh Nguyen

Prenatal inflammation may predispose to preterm birth and postnatal inflammatory disorders, such as necrotizing enterocolitis (NEC). Bioactive milk ingredients may help to support gut maturation in such neonates, but mother´s milk is often insufficient after preterm birth. We hypothesized that supplementation with bioactive ingredients from bovine milk (osteopontin, OPN; caseinoglycomacropeptide, CGMP; colostrum, COL) supports gut, immunity and NEC resistance in neonates born preterm after gram-negative infection before birth. Using preterm pigs as a model for preterm infants, fetal pigs were given intra-amniotic injections of lipopolysaccharide (LPS, 1 mg/fetus) and delivered three days later (90% gestation). For five days, groups of LPS-exposed pigs were fed formula (FOR), bovine colostrum (COL), or formula enriched with OPN or CGMP. LPS induced intra-amniotic inflammation, postnatal systemic inflammation but limited effects on postnatal gut parameters and NEC. Relative to FOR, COL feeding to LPS-exposed pigs showed less diarrhea, NEC severity, reduced gut IL-1β and IL-8 levels, greater gut goblet cell density and digestive enzyme activities, and blood helper T cell fraction. CGMP improved neonatal arousal, gut lactase activities and reduced LPS-induced IL-8 secretion in intestinal epithelial cells (IECs) in vitro. Finally, OPN tended to reduce diarrhea and stimulated IEC proliferation in vitro. No effects on villus morphology, circulating cytokines or colonic microbiota were observed among groups. In conclusion, bioactive milk ingredients exerted only modest effects on gut and systemic immune parameters in preterm pigs exposed to prenatal inflammation. Short-term, prenatal exposure to inflammation may render the gut less sensitive to immune-modulatory milk effects.

Original languageEnglish
JournalAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Volume317
Issue number1
Pages (from-to)G67-G77
ISSN0193-1857
DOIs
Publication statusPublished - 2019

ID: 218352506