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Updated: Aug 18, 2025
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
Sagori Mukhopadhyay1,2,3, Jung-Jin Lee4, Erica Hartman1,3
1Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States.
Insights
Low-risk for early-onset sepsis (EOS) infants show distinct microbiome development, with lower bacterial acquisition and different microbial composition compared to non-LRE infants. This pattern aligns with their reduced risk of EOS.
Area of Science:
- Microbiology
- Neonatal Medicine
- Genomics
Background:
- Very low birth weight (VLBW) infants often receive antibiotics due to suspected early-onset sepsis (EOS).
- A subset of VLBW infants, termed low-risk for EOS (LRE), have a sufficiently low risk to potentially avoid routine antibiotic initiation.
- Understanding microbiome differences in LRE infants is crucial for optimizing care and predicting outcomes.
Purpose of the Study:
- To compare microbiome acquisition and development between LRE and non-LRE VLBW infants.
- To investigate if reduced pathogen transmission risk in LRE infants correlates with distinct microbial profiles.
- To explore the relationship between microbiome composition and the incidence of late-onset bacteremia.
Main Methods:
- Cohort study comparing LRE (n=18) and non-LRE (n=30) VLBW infants.
- Serial shotgun metagenomic sequencing of 361 fecal samples from birth through the first weeks of life.
- Analysis of human-to-bacterial DNA ratio, microbial diversity, composition, virulence factors, and antibiotic resistance genes.
Main Results:
- LRE infants exhibited a higher human-to-bacterial DNA ratio in early fecal samples, indicating lower bacterial acquisition.
- Microbial composition differed significantly between groups from days 4-7, with *Staphylococcus epidermidis* dominating LRE infants and Enterobacteriaceae in non-LRE infants.
- Differences in microbial composition correlated with virulence and antibiotic resistance gene distribution.
- Late-onset bacteremia occurred predominantly in non-LRE infants (8 out of 9 episodes).
Conclusions:
- LRE infants demonstrate a unique microbiome development pattern associated with their low EOS risk.
- These distinct microbial profiles may influence susceptibility to infections like late-onset bacteremia.
- Further research is warranted to understand the long-term implications of these microbiome differences for VLBW infant outcomes.
Abstract:
Antibiotics are administered near-universally to very low birth weight (VLBW) infants after birth for suspected early-onset sepsis (EOS). We previously identified a phenotypic group of VLBW infants, referred to as low-risk for EOS (LRE), whose risk of EOS is low enough to avoid routine antibiotic initiation. In this cohort study, we compared 18 such infants with 30 infants categorized as non-LRE to determine if the lower risk of pathogen transmission at birth is accompanied by differences in microbiome acquisition and development. We did shotgun metagenomic sequencing of 361 fecal samples obtained serially. LRE infants had a higher human-to-bacterial DNA ratio than non-LRE infants in fecal samples on days 1-3 after birth, confirming lower bacterial acquisition among LRE infants. The microbial diversity and composition in samples from days 4-7 differed between the groups with a predominance of Staphylococcus epidermidis in LRE infants and Enterobacteriaceae sp. in non-LRE infants. Compositional differences were congruent with the distribution of virulence factors and antibiotic resistant genes. After the first week, the overall composition was similar, but changes in relative abundance for several taxa with increasing age differed between groups. Of the nine late-onset bacteremia episodes, eight occurred in non-LRE infants. Species isolated from the blood culture was detected in the pre-antibiotic fecal samples of the infant for all episodes, though these species were also found in infants without bacteremia. In conclusion, LRE infants present a distinct pattern of microbiome development that is aligned with their low risk for EOS. Further investigation to determine the impact of these differences on later outcomes such as late-onset bacteremia is warranted.
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