Dietary Bovine Lactoferrin Reduces Staphylococcus aureus in the Tissues and Modulates the Immune Response in Piglets Systemically Infected with S. aureus

Abstract

BackgroundBovine lactoferrin (bLf) reduces Staphylococcus aureus infection in premature infants and promotes the growth of Bifidobacterium infantis, a predominant infant gut species. We hypothesized that bLf in combination with B. infantis would reduce the severity of systemic S. aureus infection.ObjectiveThe aim was to determine the effects of oral administration of bLf and B. infantis on the course of systemic S. aureus infection.MethodsColostrum-deprived piglets were fed formulas containing 4 g whey/L (CON group) or bLf (LF group). One-half of the piglets in each group were gavaged with B. infantis (109 colony-forming units/d), resulting in 2 additional groups (BI or COMB, respectively). On day 7, piglets were intravenously injected with S. aureus. Blood samples were collected preinfection and every 12 h postinfection for immune analyses. Tissue samples were collected on day 12 for analysis of bacterial abundance and gene expression.ResultsPreinfection, LF piglets had lower serum interleukin 10 (IL-10), a higher percentage of lymphocytes, and a lower percentage of neutrophils than BI or COMB piglets. After infection, dietary bLf increased piglet weight gain, reduced staphylococcal counts in the kidneys, and tended to lower staphylococcal counts in the lungs and heart. Dietary bLf also decreased kidney IL-10 and increased lung interferon γ (IFN-γ) mRNA. B. infantis increased splenic IFN-γ expression. Renal Toll-like receptor 2 was upregulated in BI piglets but not in COMB piglets. Postinfection, BI piglets had increased serum IL-10 and decreased memory T cell populations. LF and COMB piglets had fewer circulating monocytes and B cells than CON or BI piglets.ConclusionsDietary bLf and B. infantis produced independent and tissue-specific effects. Piglets fed bLf alone or in combination with B. infantis mounted a more effective immune response and exhibited lower bacterial abundance. This study provides biological underpinnings to the clinical benefits of bLf observed in preterm infants but does not support B. infantis administration during S. aureus infection.

Bovine Milk Oligosaccharides and Human Milk Oligosaccharides Modulate the Gut Microbiota Composition and Volatile Fatty Acid Concentrations in a Preclinical Neonatal Model

“…DNA was isolated from AC contents and feces by combination of the QIAamp Fast DNA Stool Mini Kit (Qiagen, Valencia, CA, USA) with bead beating on the FastPrep-24 System (MP Biomedicals, Carlsbad, CA, USA), as previously described [ 36 ]. The concentration of DNA was measured with a NanoDrop 1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE, USA).…”

“…Due to the high degree of similarity in anatomy, physiology, immunology, and brain development patterns between pigs and humans, piglets are considered an ideal model for neonatal nutrition research [ 32 , 33 , 34 ]. Piglets have been extensively used as a preclinical model to study the effects of diet and prebiotics on microbiome development [ 20 , 21 , 33 , 34 , 35 , 36 , 37 ]. Therefore, the aim of the study was to evaluate the effect of HMO (2′FL + LNnT), BMOS, and a combination of BMOS and HMO on gut microbiota composition and volatile fatty acid (VFA) concentrations in a piglet model.…”

A Mediation Analysis to Identify Links between Gut Bacteria and Memory in Context of Human Milk Oligosaccharides

“…DNA was extracted from ascending colon (AC, henceforth interchangeably referred to as colonic) contents and feces by the QIAamp Fast DNA Stool Mini Kit (Qiagen, Valencia, CA, USA) in combination with bead beating on the FastPrep-24 System (MP Biomedicals, Carlsbad, CA, USA) as previously described [ 53 ]. DNA concentration was measured with a NanoDrop 1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE, USA).…”

Lactoferrin: A Critical Player in Neonatal Host Defense

“…The bactericidal activity against Gram-positive bacteria appears to be caused by the same residues as with Gram-negative bacteria [ 53 ]. Of interest, a recent study examined the effects of S. aureus bacteremia in piglets pre-treated with dietary bovine Lf [ 54 ] and found that bLf pretreatment effectively reduced S. aureus systemic infection. BLf additionally decreased IL-10 and increased interferon-γ mRNA in these animals, indicating a type 1 T helper (Th1) immune response and, thus, effects on the innate and adaptive immunity of these animals.…”