Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly

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 in...

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Main Authors: Sagori Mukhopadhyay, Jung-Jin Lee, Erica Hartman, Emily Woodford, Miren B. Dhudasia, Lisa M. Mattei, Scott G. Daniel, Kelly C. Wade, Mark A. Underwood, Kyle Bittinger
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2154091
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author Sagori Mukhopadhyay
Jung-Jin Lee
Erica Hartman
Emily Woodford
Miren B. Dhudasia
Lisa M. Mattei
Scott G. Daniel
Kelly C. Wade
Mark A. Underwood
Kyle Bittinger
author_facet Sagori Mukhopadhyay
Jung-Jin Lee
Erica Hartman
Emily Woodford
Miren B. Dhudasia
Lisa M. Mattei
Scott G. Daniel
Kelly C. Wade
Mark A. Underwood
Kyle Bittinger
author_sort Sagori Mukhopadhyay
collection DOAJ
description 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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spelling doaj-art-e1b1298cc6734a96a58ad944a3a5fb332025-08-20T03:22:16ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2154091Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assemblySagori Mukhopadhyay0Jung-Jin Lee1Erica Hartman2Emily Woodford3Miren B. Dhudasia4Lisa M. Mattei5Scott G. Daniel6Kelly C. Wade7Mark A. Underwood8Kyle Bittinger9Division of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDivision of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDivision of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDivision of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDivision of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDivision of Neonatology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United StatesDepartment of Pediatrics, University of California Davis, Sacramento, California, United StatesDepartment of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United StatesAntibiotics 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.https://www.tandfonline.com/doi/10.1080/19490976.2022.2154091Pretermmicrobiomelow-risksepsisvertical transmission
spellingShingle Sagori Mukhopadhyay
Jung-Jin Lee
Erica Hartman
Emily Woodford
Miren B. Dhudasia
Lisa M. Mattei
Scott G. Daniel
Kelly C. Wade
Mark A. Underwood
Kyle Bittinger
Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
Gut Microbes
Preterm
microbiome
low-risk
sepsis
vertical transmission
title Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
title_full Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
title_fullStr Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
title_full_unstemmed Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
title_short Preterm infants at low risk for early-onset sepsis differ in early fecal microbiome assembly
title_sort preterm infants at low risk for early onset sepsis differ in early fecal microbiome assembly
topic Preterm
microbiome
low-risk
sepsis
vertical transmission
url https://www.tandfonline.com/doi/10.1080/19490976.2022.2154091
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