Bovine lactoferrin decreases mortality in a murine model of neonatal sepsis through multiple mechanisms 4290

Description E.coli K1 is a neonatal specific pathogen that results in significant infection-related mortality in neonates but does not cause disease in healthy adults. Past data shows that neonatal mouse pups have increased intraperitoneal (IP) iron that facilitates bacterial growth. Increasing IP iron during adult infection recapitulates this bacterial burden and mortality. Neonates have a leaky gut barrier, and we hypothesized that this contributed to their increased systemic iron. We sought to improve neonatal sepsis-associated survival by enhancing intestinal barrier function and iron status. Pups were enterally supplemented with control PBS or bovine Lactoferrin (bLF), which has both iron chelating and intestinal barrier enhancing effects. Pups were then infected IP or by enteral gavage on P4-5 with E. coli K1 or control PBS. bLF decreased intestinal permeability (p < 0.0001), bacterial translocation (p < 0.001) and IP iron (p < 0.0001). Consistent with this, bLF decreased morbidity (p < 0.0001) and mortality (p < 0.05) during sepsis. Bacterial burden and markers of systemic inflammation (ie. Lipocalin-2, IL-6) were similar between groups. Further studies on immune cell kinetics and function are underway. Our results suggest that bLF promotes neonatal intestinal barrier integrity and decreases systemic free iron, resulting in improved outcomes during sepsis.