Abstract

Supplementation with probiotics in preterm infants reduces necrotizing enterocolitis and sepsis. Bovine lactoferrin is a promising supplement that may further reduce disease burden, but its effects on probiotic bacteria in human breast milk has not been evaluated. We aimed to characterise the antimicrobial activity of bovine and human lactoferrin in human breast milk against probiotics and typical neonatal sepsis pathogens. Lactoferrin levels were determined by enzyme linked immunosorbent assay in fresh and pasteurised human breast milk. The neonatal pathogens Staphylococcus epidermidis and Escherichia coli, and the probiotic Bifidobacterium breve strain M-16V were cultured in human breast milk or infant formula in the presence or absence of clinically relevant doses of bovine or human lactoferrin. Standard microbiological methods were used to determine the effects of lactoferrin on bacterial growth. Unpasteurised human breast milk contained significantly higher lactoferrin levels and resulted in superior inhibition of pathogenic bacterial growth compared to infant formula and pasteurised human breast milk. Human lactoferrin was significantly more effective at inhibiting bacterial growth, when compared to bovine lactoferrin. Supplementation with human lactoferrin or high dose bovine lactoferrin inhibited growth of the probiotic strain B. breve M-16V in pasteurised human breast milk. Although unpasteurised human breast milk and human lactoferrin had the greatest antimicrobial activity against all bacterial species tested, higher doses of bovine lactoferrin also showed activity against B. breve and. S. epidermidis. This study suggests that simultaneous administration of lactoferrins and probiotics may affect colonisation with probiotic bacteria, warranting further investigations.

Highlights

  • Preterm neonates are highly susceptible to infectious and inflammatory diseases such as lateonset sepsis (LOS) and necrotising enterocolitis (NEC) and suffer high morbidity, including long term sequelae [1]

  • We examined the growth of B. breve, S. epidermidis and E. coli in PDHM, UDHM and infant formula

  • This effect was more pronounced in UDHM, and B. breve did not show any growth above the starting inoculum (p = 0.03; Fig 2)

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Summary

Introduction

Preterm neonates are highly susceptible to infectious and inflammatory diseases such as lateonset sepsis (LOS) and necrotising enterocolitis (NEC) and suffer high morbidity, including long term sequelae [1]. A loss of microbial diversity and overgrowth of Proteobacteria in the small intestine [6, 7], can lead to a cascade of inflammation and translocation of pathogens into the bloodstream [4]. Prevention of gut dysbiosis is critical to preventing infectious and inflammatory diseases such as LOS and NEC. Human breast milk feeding is beneficial in preterm neonates and promotes development of a healthy intestinal microbiome, along with passive immune protection via a variety of soluble and cellular components [8, 9]. Lf has anti-inflammatory and immunomodulatory effects within the gut [12] Due to these properties, Lf may significantly decrease the burden of both LOS and NEC, when supplemented to preterm neonates by controlling the overgrowth of sepsis causing pathogens and decreasing inflammation in the gut [13]

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