Lactoferrin as a Treatment for Escherichia coli-associated Neonatal Sepsis

Abstract

Neonatal sepsis is considered the leading cause of infant morbidity and mortality worldwide. 2,202 neonates per 100,000 live births will develop neonatal sepsis worldwide, with an overall mortality rate that ranges from 11-19% (1). Currently, there is no consensus on the definition of neonatal sepsis (11,12). However, classically neonatal sepsis can be defined as the systemic spread of microorganisms, including bacteria, viruses, fungi, or yeast, which contribute to hemodynamic changes that challenge the immune system (9,10). Due to the difficulty in early diagnosis and treatment of neonatal sepsis, as well as the risk of developing antibiotic resistance associated with prolonged use of antibiotics, novel prevention and treatment methods such as probiotic and bioactive factors, like lactoferrin, should be considered. Lactoferrin (LF) is an iron-binding protein that shows a potential antimicrobial property, for example, antibacterial, antifungal, antiparasitic and immunomodulatory effects (16). LF is secreted by mammalian epithelial cells and can be found in body fluids such as saliva, tears, uterine secretions and milk (16). The present literature review assesses both in vitro and in vivo studies to determine whether there is sufficient evidence to support the hypothesis that LF can be used as a treatment for or prevention of E. coli-associated neonatal sepsis. This review revealed that there are many studies that have shown the effectiveness of LF against E. coli in vitro, but only few studies reported the effectiveness of LF in vivo because it is difficult to conduct a trial on sick or preterm infants. Moreover, bovine LF is the most used LF type in studies because bovine LF is the only LF type with approval from Generally Recognized As Safe (GRAS), Food Safety Authority of Ireland (FSAI) and U.S. Food and Drug Administration (FDA) to be used as a food supplement and pharmaceutical product. Furthermore, recombinant human LF shares nearly the same molecular structure with human LF. However, recombinant human LF still needs to be approved by the agencies to use it in in vivo experiments. Finally, more high-quality studies needed to support the effectiveness of LF against E. coli associated-neonatal sepsis.