PLoS One. 2013 Aug 30;8(8):e73465.

Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis.

Stewart CJ, Marrs EC, Nelson A, Lanyon C, Perry JD, Embleton ND, Cummings SP, Berrington JE.

Faculty of Health and Life Sciences, University of Northumbria, Newcastle upon Tyne, United Kingdom.



The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics.

PMID: 24023682



This paper explored the development of the gut microbiota in preterm infants from birth until discharge from a tertiary neonatal intensive care unit located in Newcastle upon Tyne, UK. This paper focused on twins and good longitudinal sampling facilitated an indepth analsysis of twins dicordant for necrotising enterocoloitis (NEC), that is one twin developed NEC (Patient 139) while the other did not (patient 140). NEC is the largest cause of mortality and morbidity in preterm infants in the developed world and despite research remains a challenging disease to prevent, diagnose and manage clinically. This paper offered important data using twins, providing the ideal diseased matched cohort, to show that Escherichia increased in abundance in the 10 days prior to the development of NEC. This genus has subsequently been categorised to species level as Escherichia coli, which is notably also present in healthy controls. Current work is currently focusing on strain level identification and the differences between the seemingly commensal E.coli and those involved in the pathology of NEC. It important that future studies go beyond sequence data to explore the functional roles of these organisms in disease causality.

Fig 1. Development of gut microbiota in twin pair 139/140 mapped to life events. P – Penicillin, G – Gentamicin, F- Fluctoxacillin, A – Amoxycillin, M – Metronidazole, s –Start of antibiotics, e – End of antibiotics, 72hr – full enteral feed (at least 150 ml/kg/day) sustained for 72 hours. a) Shannon Diversity indices (H’) of twin pair based on DGGE data. b) Turnover of the most prevalent bacterial OTUs throughout the first 36 days of life in twin 139 where antibiotics were prescribed for NEC. c) Turnover of most prevalent bacterial OTUs throughout the first 34 days of life in twin 140 where antibiotics were prescribed due to pyrexia (fever).


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