Dataset Information

Bovine Milk Oligosaccharides with Sialyllactose for Preterm Piglets.

ABSTRACT: Oligosaccharides support gut development and bacterial colonization in term infants, but it is unknown if they benefit preterm infants. Using preterm pigs, we investigated effects of bovine milk supplements enriched with oligosaccharides to improve gut development and colonization. Caesarean-delivered preterm pigs (n = 57) were reared for 19 days. The pigs were fed bovine milk supplemented with an oligosaccharide-enriched whey containing sialyllactose, or a heterogeneous oligosaccharide ingredient. To evaluate the influence of artificial rearing, near-term, vaginally born pigs raised by their sow (n = 12) were compared with artificially reared, caesarean-delivered near-term pigs (n = 14). In preterm pigs, the clinical outcome, gut function, gut microbiota, and systemic immunity were similar among dietary treatments. Natural rearing increased growth rates, gut functions, colon short chain fatty acid concentrations and bacterial diversity, relative to artificial rearing. In conclusion, supplements with bovine milk oligosaccharides were well tolerated, but did not improve gut maturation or clinical outcomes in artificially reared preterm piglets. Immaturity at birth, coupled with artificial rearing, may render the neonate unresponsive to the gut-protective effects of milk oligosaccharides. Whether bovine milk oligosaccharides may affect other endpoints (e.g., brain functions) in conditions of immaturity remains to be investigated.

SUBMITTER: Obelitz-Ryom K

PROVIDER: S-EPMC6213258 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Bovine Milk Oligosaccharides with Sialyllactose for Preterm Piglets.

Obelitz-Ryom Karina K Rendboe Amalie Katrine AK Nguyen Duc Ninh DN Rudloff Silvia S Brandt Anne Bladt AB Nielsen Dennis Sandris DS Heckmann Anne Birgitte AB Chichlowski Maciej M Sangild Per Torp PT Thymann Thomas T Bering Stine Brandt SB

Nutrients 20181012 10

Oligosaccharides support gut development and bacterial colonization in term infants, but it is unknown if they benefit preterm infants. Using preterm pigs, we investigated effects of bovine milk supplements enriched with oligosaccharides to improve gut development and colonization. Caesarean-delivered preterm pigs (n = 57) were reared for 19 days. The pigs were fed bovine milk supplemented with an oligosaccharide-enriched whey containing sialyllactose, or a heterogeneous oligosaccharide ingredie ...[more]

PMID: 30322051

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Project description:BackgroundNecrotizing enterocolitis (NEC) develops through exaggerated toll-like receptor 4 (TLR4) signaling in the intestinal epithelium. Breast milk is rich in non-digestible oligosaccharides and prevents NEC through unclear mechanisms. We now hypothesize that the human milk oligosaccharides 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL) can reduce NEC through inhibition of TLR4 signaling.MethodsNEC was induced in newborn mice and premature piglets and infant formula was supplemented with 2'-FL, 6'-SL, or lactose. Intestinal tissue was obtained at surgical resection. HMO inhibition of TLR4 was assessed in IEC-6 enterocytes, mice, and human tissue explants and via in silico modeling.ResultsSupplementation of infant formula with either 2'-FL and/or 6'-SL, but not the parent sugar lactose, reduced NEC in mice and piglets via reduced apoptosis, inflammation, weight loss, and histological appearance. Mechanistically, both 2'-FL and 6'-SL, but not lactose, reduced TLR4-mediated nuclear factor kappa light-chain enhancer of activated B cells (NF-kB) inflammatory signaling in the mouse and human intestine. Strikingly, in silico modeling revealed 2'-FL and 6'-SL, but not lactose, to dock into the binding pocket of the TLR4-MD2 complex, explaining their ability to inhibit TLR4 signaling.Conclusions2'-FL and 6'-SL, but not lactose, prevent NEC in mice and piglet models and attenuate NEC inflammation in the human ileum, in part through TLR4 inhibition.ImpactNecrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants that occurs in the setting of bacterial colonization of the gut and administration of formula feeds and activation by the innate immune receptor toll-like receptor 4 (TLR4). Breast milk prevents NEC through unclear mechanisms. We now show that breast milk-enriched human milk oligosaccharides (HMOs) that are derived from lactose prevent NEC through inhibition of TLR4. The human milk oligosaccharides 2'-FL and 6'-SL, but not the backbone sugar lactose, prevent NEC in mice and piglets. 2'-FL and 6'-SL but not lactose inhibited TLR4 signaling in cultured enterocytes, in enteroids derived from mouse intestine, and in human intestinal explants obtained at the time of surgical resection for patients with NEC. In seeking the mechanisms involved, 2'-FL and 6'-SL but not lactose were found to directly bind to TLR4, explaining the inhibition and protection against NEC. These findings may impact clinical practice by suggesting that administration of HMOs could serve as a preventive strategy for premature infants at risk for NEC development.

Dataset Information

Bovine Milk Oligosaccharides with Sialyllactose for Preterm Piglets.

Publications

Bovine Milk Oligosaccharides with Sialyllactose for Preterm Piglets.

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