TY - JOUR

T1 - Human milk oligosaccharide effects on intestinal function and inflammation after preterm birth in pigs

AU - Rasmussen, Stine Ostenfeldt

AU - Martin, Lena

AU - Østergaard, Mette Viberg

AU - Rudloff, Silvia

AU - Roggenbuck, Michael

AU - Nguyen, Duc Ninh

AU - Sangild, Per Torp

AU - Bering, Stine Brandt

N1 - CURIS 2017 NEXS 166

PY - 2017

Y1 - 2017

N2 - Human milk oligosaccharides (HMOs) may mediate prebiotic and anti-inflammatory effects in newborns. This is particularly important for preterm infants who are highly susceptible to intestinal dysfunction and necrotizing enterocolitis (NEC). We hypothesized that HMO supplementation of infant formula (IF) improves intestinal function, bacterial colonization and NEC resistance immediately after preterm birth, as tested in a preterm pig model. Mixtures of HMOs were investigated in intestinal epithelial cells and in preterm pigs (n=112) fed IF supplemented without (CON) or with a mixture of four HMOs (4-HMO) or >25 HMOs (25-HMO, 5-10 g/L given for 5 or 11 days). The 25-HMO blend decreased cell proliferation and both HMO blends decreased lipopolysaccharide-induced interleukin-8 secretion in IPEC-J2 cells, relative to control (P<.05). All HMOs were found in urine and feces of HMO-treated pigs, and short-chain fatty acids in the colon were higher in HMO vs. CON pigs (P<.05). After 5 days, NEC lesions were similar between HMO and CON pigs and 25-HMO increased colon weights (P<.01). After 11 days, the 4-HMO diet did not affect NEC (56 vs. 79%, P=.2) but increased dehydration and diarrhea (P<.05) and expression of immune-related genes (IL10, IL12, TGFβ, TLR4; P<.05). Bacterial adherence and diversity was unchanged after HMO supplementation.CONCLUSION: Complex HMO-blends affect intestinal epithelial cells in vitro and gut gene expression and fermentation in preterm pigs. However, the HMOs had limited effects on NEC and diarrhea when supplemented to IF. Longer-term exposure to HMOs may be required to improve the immature intestinal function in formula-fed preterm neonates.

AB - Human milk oligosaccharides (HMOs) may mediate prebiotic and anti-inflammatory effects in newborns. This is particularly important for preterm infants who are highly susceptible to intestinal dysfunction and necrotizing enterocolitis (NEC). We hypothesized that HMO supplementation of infant formula (IF) improves intestinal function, bacterial colonization and NEC resistance immediately after preterm birth, as tested in a preterm pig model. Mixtures of HMOs were investigated in intestinal epithelial cells and in preterm pigs (n=112) fed IF supplemented without (CON) or with a mixture of four HMOs (4-HMO) or >25 HMOs (25-HMO, 5-10 g/L given for 5 or 11 days). The 25-HMO blend decreased cell proliferation and both HMO blends decreased lipopolysaccharide-induced interleukin-8 secretion in IPEC-J2 cells, relative to control (P<.05). All HMOs were found in urine and feces of HMO-treated pigs, and short-chain fatty acids in the colon were higher in HMO vs. CON pigs (P<.05). After 5 days, NEC lesions were similar between HMO and CON pigs and 25-HMO increased colon weights (P<.01). After 11 days, the 4-HMO diet did not affect NEC (56 vs. 79%, P=.2) but increased dehydration and diarrhea (P<.05) and expression of immune-related genes (IL10, IL12, TGFβ, TLR4; P<.05). Bacterial adherence and diversity was unchanged after HMO supplementation.CONCLUSION: Complex HMO-blends affect intestinal epithelial cells in vitro and gut gene expression and fermentation in preterm pigs. However, the HMOs had limited effects on NEC and diarrhea when supplemented to IF. Longer-term exposure to HMOs may be required to improve the immature intestinal function in formula-fed preterm neonates.

U2 - 10.1016/j.jnutbio.2016.10.011

DO - 10.1016/j.jnutbio.2016.10.011

M3 - Journal article

C2 - 27889684

VL - 40

SP - 141

EP - 154

JO - Journal of Nutritional Biochemistry

JF - Journal of Nutritional Biochemistry

SN - 0955-2863

ER -