Abstract
We evaluated the impact of metal saturation of lactoferrin (with iron and manganese) on population numbers of pathogenic species relevant for neonatal sepsis that commonly originates from the gut due to bacterial translocation. Little attention has been paid to how metal ions bound to the protein affect its activity. Several reference and clinical strains as well as probiotic strains were incubated with different forms of lactoferrin: metal-depleted (apolactoferrin), iron-saturated (hololactoferrin) and manganese-saturated lactoferrin. We also attempted to confirm the observed effects of lactoferrin forms in vivo using rat pups. The observed decrease in population numbers of Gram-negative rods could not be confirmed by quantitative plating—lactoferrin may regulate these populations diversely (e.g., by anti-biofilm activity) and contribute to the inhibition of inflammatory response. We did not see any effect of lactoferrin forms on staphylococci and bifidobacteria. However, we have noted a significant increase of population numbers of Lactobacillus strains upon incubation with manganese-saturated lactoferrin. These results were confirmed in vivo in a rat model. Metal saturation is an underestimated factor regulating lactoferrin activity. Some forms are more potent in the inhibition of pathogenic species while others, such as manganese-saturated lactoferrin, could contribute to the restoration of gut homeostasis.
Highlights
The colostrum and breast milk of mammals contain extremely important nutrients for infants in the first days after delivery
We studied the influence of various lactoferrin forms on the gut microbiota by using prematurely weaned rat pups; namely, levels of potentially pathogenic E. coli as well as probiotic strains of the Lactobacillus genus
We infer that the major activity of lactoferrin does not lie in the regulation of population numbers of Gram-positive pathogenic species
Summary
The colostrum and breast milk of mammals contain extremely important nutrients for infants in the first days after delivery. They contain multiple protective peptides and proteins including an iron-binding glycoprotein, lactoferrin (Lf) The concentration of Lf is 5–13 g/L in the colostrum and 1.5–4.5 g/L in milk [1,2]. It is plausible that this protein plays an important role during neonatal development as the daily supply of Lf in an infant ranges between 0.4 g and 1.2 g/kg body weight [3]. Scientists have been developing the idea that Lf is able to modulate the newborn gastrointestinal tract microbiota composition thanks to bactericidal and bacteriostatic properties [4]. In vitro studies have proved lactoferrin’s antioxidant activity, the potential to inhibit bacterial biofilm formation and the regulation of immune cells’ response to the lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria [5].
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