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Dysbiosis Anticipating Necrotizing Enterocolitis in Very Premature Infants
Open accessAbstract
BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel disease of premature infants speculatively associated with infection. Suspected NEC can be indistinguishable from sepsis, and in established cases an infant may die within hours of diagnosis. Present treatment is supportive. A means of presymptomatic diagnosis is urgently needed. We aimed to identify microbial signatures in the gastrointestinal microbiota preceding NEC diagnosis in premature infants. METHODS: Fecal samples and clinical data were collected from a 2-year cohort of 369 premature neonates. Next-generation sequencing of 16S ribosomal RNA gene regions was used to characterize the microbiota of prediagnosis fecal samples from 12 neonates with NEC, 8 with suspected NEC, and 44 controls. Logistic regression was used to determine clinical characteristics and operational taxonomic units (OTUs) discriminating cases from controls. Samples were cultured and isolates identified using matrix-assisted laser desorption/ionization-time of flight. Clostridial isolates were typed and toxin genes detected. RESULTS: A clostridial OTU was overabundant in prediagnosis samples from infants with established NEC (P = .006). Culture confirmed the presence of Clostridium perfringens type A. Fluorescent amplified fragment-length polymorphism typing established that no isolates were identical. Prediagnosis samples from NEC infants not carrying profuse C. perfringens revealed an overabundance of a Klebsiella OTU (P = .049). Prolonged continuous positive airway pressure (CPAP) therapy with supplemental oxygen was also associated with increased NEC risk. CONCLUSIONS: Two fecal microbiota signatures (Clostridium and Klebsiella OTUs) and need for prolonged CPAP oxygen signal increased risk of NEC in presymptomatic infants. These biomarkers will assist development of a screening tool to allow very early diagnosis of NEC. Clinical Trials Registration. NCT01102738.
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“has been linked to intestinal dysbiosis in animal160 and human studies,161”
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Metadata
- Authors
- Sim, K., Shaw, A. G., Randell, P., Cox, M. J., McClure, Z. E., Li, M.-S., Haddad, M., Langford, P. R., Cookson, W. O. C. M., Moffatt, M. F., & Kroll, J. S.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Sim, K.
- Venue
- Clinical Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-10-23
- Volume
- 60
- Issue
- 3
- Pages
- 389-397
- ISSN
- 1058-4838 (ISSN-L)
- 1537-6591
- PMC
- PMC4415053
- OpenAlex
- W2105024467
- Cited by
- 224
- References
- 37
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 19 · 2023: 22 · 2022: 18 · 2021: 25 · 2020: 22 · 2019: 15 · 2018: 22 · 2017: 19 · 2016: 23 · 2015: 11
- FWCI
- 16.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Clinical Infectious Diseases (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (097117, 096964/Z/11/Z)
- National Institute for Health and Care Research (DRF-2011-04-128, 2011-04-128)
- Imperial College London
- Imperial College Healthcare NHS Trust
- Public Health England
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Keywords
- necrotizing enterocolitis, very preterm infants, gut microbiota, Clostridium perfringens, Klebsiella, presymptomatic diagnosis, biomarkers, continuous positive airway pressure, supplemental oxygen, neonatal sepsis
- MeSH terms
- Clostridium perfringens, Female, Humans, Infant, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases, Klebsiella, Male, Pregnancy, RNA, Ribosomal, 16S, Sequence Analysis, DNA, Enterocolitis, Necrotizing, Continuous Positive Airway Pressure, Dysbiosis
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