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Human milk oligosaccharides (HMOs) are reported to promote epithelial cell differentiation in vitro. The aim of the present study was to assess induction of epithelial cell differentiation by individual and combined administration of 3 HMOs. An in vitro epithelial model of the crypt-villus axis consisting of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cells was used. Cultures were randomized to 17 treatments for 72 hours of incubation: low- and high-dose HMOs (3'sialyllactose [3'SL] at 0.2 and 1.0 g/L, 6'siallylactose [6'SL] at 0.4 and 1.0 g/L, and 2'fucosyllactose at 0.2 and 2.0 g/L), HMO combinations at both low and high doses, and controls (culture medium, 4 g/L pooled HMO, and lipopolysaccharide). High doses of individual HMOs (P< 0.05), combined HMOs (P< 0.05), and pooled HMO decreased (P< 0.001) proliferation in preconfluent HT-29 cultures. Pooled means of individual low and high treatments with 3'SL and 6'SL, combinations of 2 or 3 high-dose HMOs, and total HMO significantly reduced (P< 0.05) proliferation in preconfluent Caco-2Bbe cells. HMOs increased differentiation in preconfluent HT-29 and Caco-2Bbe cells. 3'SL and 6'SL increased alkaline phosphatase activity but did not affect disaccharidase activity in postconfluent Caco-2Bbe cells. Apoptosis and necrosis were both decreased (P< 0.001) in postconfluent Caco-2Bbe cells treated with pooled HMO. HMO treatments inhibited proliferation with some associated enhancement of epithelial differentiation. Effects of HMOs were additive but no specific combinations of HMOs were especially potent. These results suggest that commercially viable individual HMOs and specific combinations may promote intestinal epithelial cell maturation.

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Parenteral nutrition is a critically important intervention for children with intestinal dysfunctions. However, total parenteral nutrition (TPN) with no enteral feeding is associated with small intestine atrophy and malabsorption, which complicate the transition to enteral nutrition. The objective of the present study was to evaluate the therapeutic potential of the intestinotrophic peptide glucagon-like peptide 2 (GLP-2), which reduces TPN-associated atrophy and maintains nutrient absorption in adult rats, for preventing nutrient malabsorption in neonates receiving TPN.

Parenteral nutrition is a critically important intervention for children with intestinal dysfunctions. However, total parenteral nutrition (TPN) with no enteral feeding is associated with small intestine atrophy and malabsorption, which complicate the transition to enteral nutrition. The objective of the present study was to evaluate the therapeutic potential of the intestinotrophic peptide glucagon‐like peptide 2 (GLP‐2), which reduces TPN‐associated atrophy and maintains nutrient absorption in adult rats, for preventing nutrient malabsorption in neonates receiving TPN. Term pigs obtained by cesarean delivery received from birth TPN alone (TPN; n = 7) or TPN with GLP‐2 (25 nmol · kg−1· d−1; GLP‐2; n = 8) or were fed sow milk enterally (n = 7). The small intestine was removed on postnatal day 6 to measure morphological responses and absorption of glucose, leucine, lysine and proline by intact tissues and brush border membrane vesicles and to quantify the abundances of mRNA and protein for enterocyte glucose transporters (SGLT‐1 and GLUT2). Relative to TPN alone, administration of GLP‐2 resulted in small intestines that were larger (P< 0.01), had greater abundances of mRNA and protein for SGLT‐1, but not for GLUT2, and had higher capacities to absorb nutrients (P< 0.01). Moreover, the intestines of GLP‐2 pigs were comparable in size and absorptive capacities with those of pigs fed sow milk enterally. Providing GLP‐2 to neonates receiving TPN prevents small intestine atrophy, results in small intestine absorptive capacities that are comparable to when nutrients are provided enterally and may accelerate the transition from TPN to enteral nutrition.

Formula-fed infants have more episodes of acute diarrhea and intestinal infection than do breast-fed infants. Nutrient additions to infant formula that could confer some of the immune benefits of breast milk to formula-fed infants are currently under investigation. This study examined the impact of enteral formulas supplemented with fermentable substrates on small intestinal lymphocyte and neutrophil migration in piglets infected with Salmonella typhimurium. Small intestinal proin-flammatory cytokine messenger RNA abundance and in vitrolipopolysaccharide-stimulated interleukin-6 release in whole blood were assessed. Piglets were randomized to receive sow milk replacer formula supplemented with methylcellulose (control), soy polysaccharides (SPS) or fructooligosaccharides (FOS). On day 7, half of the piglets were infected with S. typhimurium. Intestinal lymphocyte, neutrophil and whole blood samples were obtained on day 14. After infection, there was decreased lymphocyte migration in the control group but not in the SPS and FOS groups. The SPS group had greater neutrophil migration compared with the control and FOS groups, regardless of infection. Small intestinal abundance of proinflammatory cytokine messenger RNA was not significantly changed by either infection or diet. Blood from the FOS group challenged with lipopolysaccharide for 2 hours exhibited decreased interleukin-6 production compared with blood from the control and SPS groups, regardless of infection. Supplementation of enteral formulas with SPS maintains the migratory function of small intestinal lymphocytes while increasing that of neutrophils.

Formula-fed infants have more episodes of acute diarrhea and intestinal infection than do breast-fed infants. Nutrient additions to infant formula that could confer some of the immune benefits of breast milk to formula-fed infants are currently under investigation. This study examined the impact of enteral formulas supplemented with fermentable substrates on small intestinal lymphocyte and neutrophil migration in piglets infected with Salmonella typhimurium. Small intestinal proin-flammatory cytokine messenger RNA abundance and in vitrolipopolysaccharide-stimulated interleukin-6 release in whole blood were assessed.