Gut microbial colonisation in premature neonates predicts neonatal sepsis
Open accessAbstract
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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In studies of the gut microbiome in critically ill patients, butyrate-producing bacteria are uncommon or absent, and butyrate production is at a minimum.
“In studies of the gut microbiome in critically ill patients, butyrate-producing bacteria are uncommon or absent,20,69–71 and butyrate production is at a minimum.”
From The microbiome and critical illness (2016) · cites this paper as [70]
The lower gastrointestinal tract in critical illness loses diversity and the community is overrun by a few bacterial species.
“The lower gastrointestinal tract, which in healthy people contains hundreds of distinct bacterial species, loses diversity, and the community is overrun by a few (in some cases only one) bacterial species.”
From The microbiome and critical illness (2016) · cites this paper as [70]
Dominant species in the lower gastrointestinal tract of critically ill patients include S aureus, Enterococcus spp, and members of the Enterobacteriaceae family.
“Dominant species include S aureus, Enterococcus spp, and members of the Enterobacteriaceae family (including E coli and Klebsiella spp).”
From The microbiome and critical illness (2016) · cites this paper as [70]
In multiple studies, the composition of the early gut microbiome has been predictive of neonatal sepsis.
“In multiple studies, the composition of the early gut microbiome has been predictive of neonatal sepsis,70,156,157”
From The microbiome and critical illness (2016) · cites this paper as [70]
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- Authors
- Madan, J. C., Salari, R. C., Saxena, D., Davidson, L., O'Toole, G. A., Moore, J. H., Sogin, M. L., Foster, J. A., Edwards, W. H., Palumbo, P., & Hibberd, P. L.
- Affiliations
- Dartmouth–Hitchcock Medical Center (US)
- Computational Genetics, Dartmouth Medical School, Lebanon, New Hampshire, USA
- Tufts Medical Center (US)
- Department of Microbiology & Immunology, Dartmouth Medical School, Hanover, New Hampshire, USA
- Dartmouth College (US)
- Marine Biological Laboratory (US)
- University of Idaho (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Madan, Juliette C
- ORCID
- Venue
- Archives of Disease in Childhood - Fetal and Neonatal Edition
- Publisher
- BMJ
- Published
- 2012-05-06
- Volume
- 97
- Issue
- 6
- Pages
- F456-F462
- ISSN
- 1359-2998 (ISSN-L)
- 1468-2052
- PMC
- PMC3724360
- OpenAlex
- W2149181253
- Cited by
- 340
- References
- 51
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 25 · 2023: 18 · 2022: 22 · 2021: 27 · 2020: 28 · 2019: 44 · 2018: 32 · 2017: 20 · 2016: 29 · 2015: 29 · 2014: 25 · 2013: 17 · 2012: 5
- FWCI
- 23.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Archives of Disease in Childhood Fetal & Neonatal (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation (0939454)
- Cystic Fibrosis Foundation (STANTO07R0)
- Hitchcock Foundation
- Dartmouth College
- National Institutes of Health (NIH-R01, AI59694, P20RR16448, 5p20rr018787-07)
- National Cancer Institute (P30CA023108)
- National Institute of Allergy and Infectious Diseases (R01AI083256, R01 AI59694, R01AI059694)
- National Center for Research Resources (P20-RR018787, P20RR016454, P20RR16448, P20RR016448)
- Division of Biological Infrastructure
- National Center for Complementary and Integrative Health (K24AT003683, U01AT002388)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Keywords
- neonatal sepsis, gut microbiota, preterm infants, very low birth weight infants, intestinal bacterial translocation, microbial diversity, Staphylococcus, empirical antibiotic therapy, probiotics, 16S rRNA gene sequencing, Klebsiella, Veillonella
- MeSH terms
- Anti-Bacterial Agents, Base Sequence, Enterobacteriaceae, Humans, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Longitudinal Studies, Meconium, Molecular Sequence Data, Risk Factors, RNA, Messenger, Staphylococcus, Colony Count, Microbial, Sepsis, Bacterial Translocation, Infant, Very Low Birth Weight, Gastrointestinal Tract
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