Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs

Background: Preterm infants are born with an immature immune system, limited passive immunity, and are at risk of developing bacteremia and sepsis in the postnatal period. We hypothesized that enteral feeding, with or without added immunoglobulins, improves the clinical response to systemic infectio...

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Main Authors: Ole Bæk, Anders Brunse, Duc Ninh Nguyen, Arshnee Moodley, Thomas Thymann, Per Torp Sangild
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-05-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2020.01019/full
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author Ole Bæk
Anders Brunse
Duc Ninh Nguyen
Arshnee Moodley
Thomas Thymann
Per Torp Sangild
Per Torp Sangild
Per Torp Sangild
author_facet Ole Bæk
Anders Brunse
Duc Ninh Nguyen
Arshnee Moodley
Thomas Thymann
Per Torp Sangild
Per Torp Sangild
Per Torp Sangild
author_sort Ole Bæk
collection DOAJ
description Background: Preterm infants are born with an immature immune system, limited passive immunity, and are at risk of developing bacteremia and sepsis in the postnatal period. We hypothesized that enteral feeding, with or without added immunoglobulins, improves the clinical response to systemic infection by coagulase negative staphylococci.Methods: Using preterm cesarean delivered pigs as models for preterm infants, we infused live Staphylococcus epidermidis (SE, 5 × 109 colony forming units per kg) systemically 0–3 days after birth across five different experiments. SE infection responses were assessed following different gestational age at birth (preterm vs. term), enteral milk diets (bovine colostrum, infant formula with or without added porcine plasma) and with/without systemic immunoglobulins. Pigs infected with SE were assessed 12–48 h for clinical variables, blood bacteriology, chemistry, hematology, and gut dysfunction (intestinal permeability, necrotizing enterocolitis lesions).Results: Adverse clinical responses and increased mortality were observed in preterm vs. term pigs, when infected with SE just after birth. Feeding bovine colostrum just after birth improved blood SE clearance and clinical status (improved physical activity and intestinal structure, fewer bone marrow bacteria), relative to pigs fed infant formula. A few days later, clinical responses to SE bacteremia (hematology, neutrophil phagocytic capacity, T cell subsets) were less severe, and less affected by different milk diets, with or without added immunoglobulins.Conclusion: Prematurity increases the sensitivity of newborn pigs to SE bacteremia, potentially causing sepsis. Sensitivity to systemic SE infection decreases rapidly in the days after preterm birth. Both age and diet (parenteral nutrition, colostrum, milk, formula) may influence gut inflammation, bacterial translocation and systemic immune development in the days after birth in preterm newborns.
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spelling doaj.art-b6279094444a4c6fb45402ff8c76ee182022-12-21T18:32:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.01019502085Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm PigsOle Bæk0Anders Brunse1Duc Ninh Nguyen2Arshnee Moodley3Thomas Thymann4Per Torp Sangild5Per Torp Sangild6Per Torp Sangild7Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkComparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkComparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkVeterinary Clinical Microbiology, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkComparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkComparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Neonatology, Rigshospitalet, Copenhagen, DenmarkDepartment of Pediatrics, Odense University Hospital, Odense, DenmarkBackground: Preterm infants are born with an immature immune system, limited passive immunity, and are at risk of developing bacteremia and sepsis in the postnatal period. We hypothesized that enteral feeding, with or without added immunoglobulins, improves the clinical response to systemic infection by coagulase negative staphylococci.Methods: Using preterm cesarean delivered pigs as models for preterm infants, we infused live Staphylococcus epidermidis (SE, 5 × 109 colony forming units per kg) systemically 0–3 days after birth across five different experiments. SE infection responses were assessed following different gestational age at birth (preterm vs. term), enteral milk diets (bovine colostrum, infant formula with or without added porcine plasma) and with/without systemic immunoglobulins. Pigs infected with SE were assessed 12–48 h for clinical variables, blood bacteriology, chemistry, hematology, and gut dysfunction (intestinal permeability, necrotizing enterocolitis lesions).Results: Adverse clinical responses and increased mortality were observed in preterm vs. term pigs, when infected with SE just after birth. Feeding bovine colostrum just after birth improved blood SE clearance and clinical status (improved physical activity and intestinal structure, fewer bone marrow bacteria), relative to pigs fed infant formula. A few days later, clinical responses to SE bacteremia (hematology, neutrophil phagocytic capacity, T cell subsets) were less severe, and less affected by different milk diets, with or without added immunoglobulins.Conclusion: Prematurity increases the sensitivity of newborn pigs to SE bacteremia, potentially causing sepsis. Sensitivity to systemic SE infection decreases rapidly in the days after preterm birth. Both age and diet (parenteral nutrition, colostrum, milk, formula) may influence gut inflammation, bacterial translocation and systemic immune development in the days after birth in preterm newborns.https://www.frontiersin.org/article/10.3389/fimmu.2020.01019/fullsepsisbacteremiapreterminfantdietimmunity
spellingShingle Ole Bæk
Anders Brunse
Duc Ninh Nguyen
Arshnee Moodley
Thomas Thymann
Per Torp Sangild
Per Torp Sangild
Per Torp Sangild
Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
Frontiers in Immunology
sepsis
bacteremia
preterm
infant
diet
immunity
title Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
title_full Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
title_fullStr Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
title_full_unstemmed Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
title_short Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
title_sort diet modulates the high sensitivity to systemic infection in newborn preterm pigs
topic sepsis
bacteremia
preterm
infant
diet
immunity
url https://www.frontiersin.org/article/10.3389/fimmu.2020.01019/full
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AT arshneemoodley dietmodulatesthehighsensitivitytosystemicinfectioninnewbornpretermpigs
AT thomasthymann dietmodulatesthehighsensitivitytosystemicinfectioninnewbornpretermpigs
AT pertorpsangild dietmodulatesthehighsensitivitytosystemicinfectioninnewbornpretermpigs
AT pertorpsangild dietmodulatesthehighsensitivitytosystemicinfectioninnewbornpretermpigs
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