Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome.
Methods Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis.
Results Six neonates were 24–27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella.
Conclusions In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a ‘healthy microbiome’ present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates.
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Funding The Hearst Foundation, The Synergy Grant (Dartmouth), The Joshua Burnett Career Development Award through the Hitchcock Foundation (Dartmouth), the Department of Pediatrics, Dartmouth. This work was also supported by a pilot grant from the Cystic Fibrosis Foundation Research Development Program (STANTO07R0). RCS and JHM were funded by NIH R01 AI59694. JAF was funded in part by NIH grants P20RR16448 and P20RR016454 and by NSF DBI0939454.
Competing interests None.
Patient consent Obtained.
Ethics approval Dartmouth College CPHS IRB.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The authors have provided open access to their sequencing data to other scientists by publishing the sequencing data in the following location: all new data generated from sequencing has been deposited in NCBI GenBank (SRA) with accession number SRA043957.1.
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