Oral Supplementation with Bovine Colostrum Prevents Septic Shock and Brain Barrier Disruption During Bloodstream Infection in Preterm Newborn Pigs

Anders Brunse, Päivi Worsøe, Susanne Elisabeth Pors, Kerstin Skovgaard, Per Torp Sangild*

*Corresponding author for this work

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Abstract

Preterm infants have increased risk of neonatal sepsis, potentially inducing brain injury, and they may benefit from early initiation of enteral milk feeding. Using preterm pigs as models, we hypothesized that early provision of bovine colostrum to parentally nourished newborns protects against sepsis and neuroinflammation during bloodstream infection. Preterm newborn pigs were administered 109 CFU/kg of intra-arterial Staphylococcus epidermidis (SE, an opportunistic pathogen often causing sepsis in preterm infants), followed by administration of total parenteral nutrition (TPN, SE + TPN, n = 15) or oral provision of bovine colostrum with supplementary parenteral nutrition (SE + COL, n = 14), and compared with uninfected, TPN-nourished controls (CON + TPN, n = 11). SE-infected animals showed multiple signs of sepsis, including lethargy, hypotension, respiratory acidosis, internal organ hemorrhages, cellular responses (leukopenia, thrombocytopenia), brain barrier disruption and neuroinflammation. At 24 h, colostrum supplementation reduced the SE abundance in blood and cerebrospinal fluid (CSF, both p < 0.05). Further, colostrum feeding normalized arterial blood pressure (38.5 ± 1.20 vs 30.6 ± 3.79 mmHg), pH (7.37 ± 0.02 vs 7.10 ± 0.07) and lactate (1.01 ± 0.11 vs 4.20 ± 1.20 mM, all p < 0.05), and increased motor activity, to levels in controls (p < 0.001). Finally, colostrum-fed animals showed reduced blood-CSF barrier permeability and CSF leukocyte levels, and this was accompanied by normalized gene expression of tight junction proteins (Occludin, Claudin-5, both p < 0.05) and reduced expression of leukocyte chemoattractants (CXCL9-11, all p < 0.01). Early oral supplementation with bovine colostrum prevents septic shock and ameliorates brain barrier disruption and neuroinflammation during bloodstream infection in preterm pigs. Bovine colostrum supplementation may improve resistance against systemic infection in immature, immune-compromised preterm infants.
Original languageEnglish
JournalSchock
Volume51
Issue number3
Pages (from-to)337-347
ISSN1073-2322
DOIs
Publication statusPublished - 2019

Keywords

  • Blood-brain barrier
  • Bovine colostrum
  • Brain injury
  • Neonatal sepsis
  • Staphylococcus epidermidis
  • Preterm birth

Cite this

Brunse, Anders ; Worsøe, Päivi ; Pors, Susanne Elisabeth ; Skovgaard, Kerstin ; Sangild, Per Torp. / Oral Supplementation with Bovine Colostrum Prevents Septic Shock and Brain Barrier Disruption During Bloodstream Infection in Preterm Newborn Pigs. In: Schock. 2019 ; Vol. 51, No. 3. pp. 337-347.
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abstract = "Preterm infants have increased risk of neonatal sepsis, potentially inducing brain injury, and they may benefit from early initiation of enteral milk feeding. Using preterm pigs as models, we hypothesized that early provision of bovine colostrum to parentally nourished newborns protects against sepsis and neuroinflammation during bloodstream infection. Preterm newborn pigs were administered 109 CFU/kg of intra-arterial Staphylococcus epidermidis (SE, an opportunistic pathogen often causing sepsis in preterm infants), followed by administration of total parenteral nutrition (TPN, SE + TPN, n = 15) or oral provision of bovine colostrum with supplementary parenteral nutrition (SE + COL, n = 14), and compared with uninfected, TPN-nourished controls (CON + TPN, n = 11). SE-infected animals showed multiple signs of sepsis, including lethargy, hypotension, respiratory acidosis, internal organ hemorrhages, cellular responses (leukopenia, thrombocytopenia), brain barrier disruption and neuroinflammation. At 24 h, colostrum supplementation reduced the SE abundance in blood and cerebrospinal fluid (CSF, both p < 0.05). Further, colostrum feeding normalized arterial blood pressure (38.5 ± 1.20 vs 30.6 ± 3.79 mmHg), pH (7.37 ± 0.02 vs 7.10 ± 0.07) and lactate (1.01 ± 0.11 vs 4.20 ± 1.20 mM, all p < 0.05), and increased motor activity, to levels in controls (p < 0.001). Finally, colostrum-fed animals showed reduced blood-CSF barrier permeability and CSF leukocyte levels, and this was accompanied by normalized gene expression of tight junction proteins (Occludin, Claudin-5, both p < 0.05) and reduced expression of leukocyte chemoattractants (CXCL9-11, all p < 0.01). Early oral supplementation with bovine colostrum prevents septic shock and ameliorates brain barrier disruption and neuroinflammation during bloodstream infection in preterm pigs. Bovine colostrum supplementation may improve resistance against systemic infection in immature, immune-compromised preterm infants.",
keywords = "Blood-brain barrier, Bovine colostrum, Brain injury, Neonatal sepsis, Staphylococcus epidermidis, Preterm birth",
author = "Anders Brunse and P{\"a}ivi Wors{\o}e and Pors, {Susanne Elisabeth} and Kerstin Skovgaard and Sangild, {Per Torp}",
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language = "English",
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pages = "337--347",
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Oral Supplementation with Bovine Colostrum Prevents Septic Shock and Brain Barrier Disruption During Bloodstream Infection in Preterm Newborn Pigs. / Brunse, Anders; Worsøe, Päivi; Pors, Susanne Elisabeth; Skovgaard, Kerstin; Sangild, Per Torp.

In: Schock, Vol. 51, No. 3, 2019, p. 337-347.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Oral Supplementation with Bovine Colostrum Prevents Septic Shock and Brain Barrier Disruption During Bloodstream Infection in Preterm Newborn Pigs

AU - Brunse, Anders

AU - Worsøe, Päivi

AU - Pors, Susanne Elisabeth

AU - Skovgaard, Kerstin

AU - Sangild, Per Torp

PY - 2019

Y1 - 2019

N2 - Preterm infants have increased risk of neonatal sepsis, potentially inducing brain injury, and they may benefit from early initiation of enteral milk feeding. Using preterm pigs as models, we hypothesized that early provision of bovine colostrum to parentally nourished newborns protects against sepsis and neuroinflammation during bloodstream infection. Preterm newborn pigs were administered 109 CFU/kg of intra-arterial Staphylococcus epidermidis (SE, an opportunistic pathogen often causing sepsis in preterm infants), followed by administration of total parenteral nutrition (TPN, SE + TPN, n = 15) or oral provision of bovine colostrum with supplementary parenteral nutrition (SE + COL, n = 14), and compared with uninfected, TPN-nourished controls (CON + TPN, n = 11). SE-infected animals showed multiple signs of sepsis, including lethargy, hypotension, respiratory acidosis, internal organ hemorrhages, cellular responses (leukopenia, thrombocytopenia), brain barrier disruption and neuroinflammation. At 24 h, colostrum supplementation reduced the SE abundance in blood and cerebrospinal fluid (CSF, both p < 0.05). Further, colostrum feeding normalized arterial blood pressure (38.5 ± 1.20 vs 30.6 ± 3.79 mmHg), pH (7.37 ± 0.02 vs 7.10 ± 0.07) and lactate (1.01 ± 0.11 vs 4.20 ± 1.20 mM, all p < 0.05), and increased motor activity, to levels in controls (p < 0.001). Finally, colostrum-fed animals showed reduced blood-CSF barrier permeability and CSF leukocyte levels, and this was accompanied by normalized gene expression of tight junction proteins (Occludin, Claudin-5, both p < 0.05) and reduced expression of leukocyte chemoattractants (CXCL9-11, all p < 0.01). Early oral supplementation with bovine colostrum prevents septic shock and ameliorates brain barrier disruption and neuroinflammation during bloodstream infection in preterm pigs. Bovine colostrum supplementation may improve resistance against systemic infection in immature, immune-compromised preterm infants.

AB - Preterm infants have increased risk of neonatal sepsis, potentially inducing brain injury, and they may benefit from early initiation of enteral milk feeding. Using preterm pigs as models, we hypothesized that early provision of bovine colostrum to parentally nourished newborns protects against sepsis and neuroinflammation during bloodstream infection. Preterm newborn pigs were administered 109 CFU/kg of intra-arterial Staphylococcus epidermidis (SE, an opportunistic pathogen often causing sepsis in preterm infants), followed by administration of total parenteral nutrition (TPN, SE + TPN, n = 15) or oral provision of bovine colostrum with supplementary parenteral nutrition (SE + COL, n = 14), and compared with uninfected, TPN-nourished controls (CON + TPN, n = 11). SE-infected animals showed multiple signs of sepsis, including lethargy, hypotension, respiratory acidosis, internal organ hemorrhages, cellular responses (leukopenia, thrombocytopenia), brain barrier disruption and neuroinflammation. At 24 h, colostrum supplementation reduced the SE abundance in blood and cerebrospinal fluid (CSF, both p < 0.05). Further, colostrum feeding normalized arterial blood pressure (38.5 ± 1.20 vs 30.6 ± 3.79 mmHg), pH (7.37 ± 0.02 vs 7.10 ± 0.07) and lactate (1.01 ± 0.11 vs 4.20 ± 1.20 mM, all p < 0.05), and increased motor activity, to levels in controls (p < 0.001). Finally, colostrum-fed animals showed reduced blood-CSF barrier permeability and CSF leukocyte levels, and this was accompanied by normalized gene expression of tight junction proteins (Occludin, Claudin-5, both p < 0.05) and reduced expression of leukocyte chemoattractants (CXCL9-11, all p < 0.01). Early oral supplementation with bovine colostrum prevents septic shock and ameliorates brain barrier disruption and neuroinflammation during bloodstream infection in preterm pigs. Bovine colostrum supplementation may improve resistance against systemic infection in immature, immune-compromised preterm infants.

KW - Blood-brain barrier

KW - Bovine colostrum

KW - Brain injury

KW - Neonatal sepsis

KW - Staphylococcus epidermidis

KW - Preterm birth

U2 - 10.1097/SHK.0000000000001131

DO - 10.1097/SHK.0000000000001131

M3 - Journal article

VL - 51

SP - 337

EP - 347

JO - Schock

JF - Schock

SN - 1073-2322

IS - 3

ER -