Abstract

ObjectiveLate onset sepsis (LOS) contributes to mortality and morbidity in preterm infants. We tested the hypotheses that microbes causing LOS originate from the gut, and that distortions in the gut microbial community increases subsequent risk of LOS.Study DesignWe examined the gut microbial community in prospectively collected stool samples from preterm infants with LOS and an equal number of age-matched controls at two sites (Cincinnati, OH and Birmingham, AL), by sequencing the bacterial 16S rDNA. We confirmed our findings in a subset of infants by whole genome shotgun sequencing, and analyzed the data using R and LEfSe.ResultsInfants with LOS in Cincinnati, as compared to controls, had less abundant Actinobacteria in the first samples after birth (median 18 days before sepsis onset), and less abundant Pseudomonadales in the last samples collected prior to LOS (median 8 days before sepsis onset). Infants with LOS in Birmingham, as compared to controls, had no differences identified in the first sample microbial communities, but Lactobacillales was less abundant in the last samples prior to LOS (median 4 days before sepsis onset). Sequencing identified detectable levels of the sepsis-causative organism in stool samples prior to disease onset for 82% of LOS cases.ConclusionsTranslocation of gut microbes may account for the majority of LOS cases. Distortions in the fecal microbiota occur prior to LOS, but the form of distortion depends on timing and site. The microbial composition of fecal samples does not predict LOS onset in a generalizable fashion.

Highlights

  • Late-onset neonatal sepsis (LOS) is a major cause of morbidity and mortality in preterm infants

  • Infants with LOS in Birmingham, as compared to controls, had no differences identified in the first sample microbial communities, but Lactobacillales was less abundant in the last samples prior to LOS

  • Sequencing identified detectable levels of the sepsis-causative organism in stool samples prior to disease onset for 82% of LOS cases

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Summary

Introduction

Late-onset neonatal sepsis (LOS) is a major cause of morbidity and mortality in preterm infants. Several small studies have demonstrated that the majority of LOS cases, in particular, those caused by group B Streptococcus, Serratia marcescens, or Escherichia coli strains, are due to organisms that were detectable in infant stool samples collected prior to the occurrence of sepsis [6, 7]. A study of six infants found that those who later developed sepsis had an intestinal microbiota distinct from that of healthy infants [8]; samples from infants who later developed LOS tended to have more Staphylococcus and Proteobacteria than healthy infants who exhibited greater microbial diversity and more anaerobic bacteria [8]. A third study, of 27 infants, found an increase in Staphylococcaceae associated with sepsis but did not report a difference in diversity between cases and controls [10]

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