Killing the messenger in the nick of time: Persistence of breast milk sCD14 in the neonatal gastrointestinal tract

Human breast milk contains several proteins that supplement the newborn mucosal defense system and prevent gastrointestinal illnesses. One of these recently identified breast milk proteins is soluble CD14 (sCD14). By being an important component of the lipopolysaccharide (LPS) receptor complex, it has been suggested that breast milk sCD14 could stimulate the newborn immune system and help reduce gastrointestinal Gram-negative infections. However, to deliver its potential immune benefits to the neonate, sCD14 would have to survive the passage through the gastrointestinal tract and retain its biologic activity. We analyzed the presence of breast milk sCD14 in the neonatal digestive system and found breast milk sCD14 to be absent from the stools of breast-fed infants. In vitro digestion analysis with simulated gastric and pancreatic fluids revealed that sCD14 is likely to survive the pepsin digestion but is more prone to been nicked and digested by pancreatin. These findings suggest that the presence of intact breast milk sCD14 in the upper digestive system could promote innate immunity in this low bacteria density lumen. The low concentration of sCD14 in the LPS-rich environment of the distal gastrointestinal tract (i.e. commensal microflora) could prevent excessive inflammation.