Lactoferrin and necrotizing enterocolitis

Abstract

Lactoferrin (LF) is a multifunctional protein and a member of the transferrin family. LF and lysozyme in breast milk kill bacteria. In the stomach, pepsin digests and releases a potent peptide antibiotic called lactoferricin from native LF. The antimicrobial characteristics of LF may facilitate a healthy intestinal microbiome. LF is the major whey in human milk; its highest concentration is in colostrum. This fact highlights early feeding of colostrum and also fresh mature milk as a way to prevent necrotizing enterocolitis.

Figure 1. Four Major Actions of Lactoferrin That May Act to Prevent Necrotizing Enterocolitis

Figure 2. Anti-inflammatory and Immuno-regulatory Effects of Lactoferrin in Small Neonatal Intestine

Lactoferrin (LF) binds a number of bacterial components including cell wall-associated lipopolysaccharide (LPS), flagellin, and DNA (CpG). This binding inhibits the bacterial components from initiating an inflammatory response. LF also binds to Gram-positive or Gram-negative bacteria either killing the microbe or hindering its invasion of tissue. LF engages pattern recognition receptors (i.e., Toll-like receptors [TLR], CD14 receptor) on gut-related epithelia and thereby restricts transduction of a pro-inflammatory signal or microbial translocation. By adhering to its own receptor, the lipid raft Intelectin, LF further limits infection. Importantly, LF activates dendritic cells (DCs) as they provide surveillance of the gut lumen. This LF-initiated signaling mediates secretion of intereukin-12 by DCs which in turn stops interleukin-4 production by Th2 cells and reverses apoptotic death of Th1 cells. This process creates a competent Th1 helper cell population and restores a proper Th1/Th2 balance that can resist infection.