Rapid Cerebral Metabolic Shift during Neonatal Sepsis Is Attenuated by Enteral Colostrum Supplementation in Preterm Pigs.

Masoumeh Alinaghi,Anders Brunse,Per Sangild,Ping-Ping Jiang,Hanne Bertram

doi:10.3390/metabo9010013

Masoumeh Alinaghi, Anders Brunse + Show 3 more

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https://doi.org/10.3390/metabo9010013

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Abstract

Sepsis, the clinical manifestation of serious infection, may disturb normal brain development, especially in preterm infants with an immature brain. We hypothesized that neonatal sepsis induces systemic metabolic alterations that rapidly affect metabolic signatures in immature brain and cerebrospinal fluid (CSF). Cesarean-delivered preterm pigs systemically received 109 CFU/kg Staphylococcus epidermidis (SE) and were provided total parenteral nutrition (n = 9) or enteral supplementation with bovine colostrum (n = 10) and compared with uninfected pigs receiving parenteral nutrition (n = 7). Plasma, CSF, and brain tissue samples were collected after 24 h and analyzed by 1H NMR-based metabolomics. Both plasma and CSF metabolomes revealed SE-induced changes in metabolite levels that reflected a modified energy metabolism. Hence, increased plasma lactate, alanine, and succinate levels, as well as CSF lactate levels, were observed during SE infection (all p < 0.05, ANOVA analysis). Myo-inositol, a glucose derivative known for beneficial effects on lung maturation in preterm infants, was also increased in plasma and CSF following SE infection. Enteral colostrum supplementation attenuated the lactate accumulation in blood and CSF. Bloodstream infection in preterm newborns was found to induce a rapid metabolic shift in both plasma and CSF, which was modulated by colostrum feeding.

Highlights

Sepsis, the clinical manifestation of an uncontrolled bloodstream infection (BSI), is a frequent cause of morbidity and mortality in newborns, especially in preterm infants with very low birth weight [1].Coagulase-negative staphylococci are among the most frequent pathogens in neonatal sepsis, Staphylococcus epidermidis (SE), which is often acquired from the hospital environment through invasive medical devices [2]
cerebrospinal fluid (CSF), blood plasma, and six brain areas of interest from preterm newborn pigs were analyzed by 1 H NMR and high-resolution magic-angle spinning (HR-MAS) NMR
Spectroscopy, and a total of 31, 36, and 26 metabolites were assigned in CSF, plasma, and brain tissues, respectively (Figures 1 and 2)

Summary

Introduction

The clinical manifestation of an uncontrolled bloodstream infection (BSI), is a frequent cause of morbidity and mortality in newborns, especially in preterm infants with very low birth weight [1].Coagulase-negative staphylococci are among the most frequent pathogens in neonatal sepsis, Staphylococcus epidermidis (SE), which is often acquired from the hospital environment through invasive medical devices [2]. An elevated level of proinflammatory cytokines, as part of the infection-related inflammatory response, is neurotoxic and increases the permeability of the blood–brain barrier and may cause neurodevelopmental impairments [8,9]. Exposure to neonatal systemic infection leads to central nervous system (CNS) inflammation, potentially causing brain injury with long-lasting consequences for neurological and mental health [6,10]. It remains unclear if the infection-induced systemic inflammatory reactions are associated with rapid metabolic perturbations in the cerebrospinal fluid (CSF) and the immature brain. Systemic metabolic adaptations during neonatal sepsis have been demonstrated [14] but the effect on cerebral energy metabolism is less known, though it may be of importance

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