(41) Enteral Supplementation with Bovine Lactoferrin or Glutamine Alters Neonatal Iron Status, Intestinal Permeability and Sepsis-related Mortality in a Mouse Model

Background: A murine model of E. coli sepsis results in significant mortality in pups but universal survival in adults despite equivalent immune responses, suggesting that neonatal susceptibility is due to immune-independent factors. Previous data shows that increased intraperitoneal(IP) iron in pups contributes to increased E. coli growth and subsequent mortality. Neonates are also known to have decreased intestinal barrier function.

Objectives: We hypothesized this iron-rich depot was due to a leaky intestinal barrier allowing iron to more freely pass from the intestinal lumen into the IP cavity.

Design/Methods: To determine if altering intestinal barrier function would influence sepsis-associated mortality, neonates were enterally gavaged with lactoferrin(LF) or glutamine(Gln) daily. Intestinal permeability, iron status and E. coli K1sepsis-associated mortality and morbidity were determined on postnatal day 4/5. Lipocalin, lysozyme and hepcidin levels were also assessed following supplementation

Results: LF decreased intestinal permeability when measured by FITC-dextran assay(p < 0.0001) and resulted in less IP iron (p < 0.0001). LF also resulted in decreased E.coli translocation following E.coli oral gavage sepsis(p=0.0011) and decreased mortality following E.coli IP sepsis(p < 0.05). Gln increased intestinal permeability when measured by FITC-dextran assay(p < 0.0001) but had no effect on IP iron. Gln increased E.coli translocation(p < 0.05) and burden(p < 0.05) following E.coli oral gavage sepsis. Gln also increased mortality following E.coli IP sepsis(p < 0.05).
Lipocalin was increased in both LF and Gln supplemented pups at baseline in a biologically relevant but not statistically significant manner. Lysozyme levels were the same in all groups at 12 hours post infection (hpi). Interestingly, the neonatal pups did not upregulate hepcidin at 6 nor 12 hpi in response to infection in any supplementation group.

Conclusion: Early-life supplementation can alter intestinal permeability and iron status, and these alterations influence neonatal E.coli sepsis-associated mortality. Further studies to elucidate the mechanism of action are required.