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

ABSTRACT: 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.

SUBMITTER: Stewart CJ

PROVIDER: S-EPMC3758342 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Stewart Christopher J CJ Marrs Emma C L EC Nelson Andrew A Lanyon Clare C Perry John D JD Embleton Nicholas D ND Cummings Stephen P SP Berrington Janet E JE

PloS one 20130830 8

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 triple ...[more]

PMID: 24023682

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Project description:BackgroundFeeding practices around the time of packed red blood cell transfusion have been implicated in the subsequent development of necrotising enterocolitis (NEC) in preterm infants. Specifically, it has been suggested that withholding feeds around the time of transfusion may reduce the risk of subsequent NEC. It is important to determine if withholding feeds around transfusion reduces the risk of subsequent NEC and associated mortality.Objectives• To assess the benefits and risks of stopping compared to continuing feed management before, during, and after blood transfusion in preterm infants • To assess the effects of stopping versus continuing feeds in the following subgroups of infants: infants of different gestations; infants with symptomatic and asymptomatic anaemia; infants who received different feeding schedules, types of feed, and methods of feed delivery; infants who were transfused with different blood products, at different blood volumes, via different routes of delivery; and those who received blood transfusion with and without co-interventions such as use of diuretics • To determine the effectiveness and safety of stopping feeds around the time of a blood transfusion in reducing the risk of subsequent necrotising enterocolitis (NEC) in preterm infants SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), in the Cochrane Library; MEDLINE (1966 to 14 November 2018); Embase (1980 to 14 November 2018); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 November 2018). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs.Selection criteriaRandomised and quasi-randomised controlled trials that compared stopping feeds versus continuing feeds around the time of blood transfusion in preterm infants.Data collection and analysisTwo review authors independently selected trials, assessed trial quality, and extracted data from the included studies.Main resultsThe search revealed seven studies that assessed effects of stopping feeds during blood transfusion. However, only one RCT involving 22 preterm infants was eligible for inclusion in the review. This RCT had low risk of selection bias but high risk of performance bias, as care personnel were not blinded to the study allocation. The primary objective of this trial was to investigate changes in mesenteric blood flow, and no cases of NEC were reported in any of the infants included in the trial. We were unable to draw any conclusions from this single study. The overall GRADE rating for quality of evidence was very low.Authors' conclusionsRandomised controlled trial evidence is insufficient to show whether stopping feeds has an effect on the incidence of subsequent NEC or death. Large, adequately powered RCTs are needed to address this issue.

Project description:BackgroundPreterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression.ResultsClinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0-90%) at ≤ 2 weeks, 69.7% (29.9-86.9%) in the 3rd, and 75.5% (54.5-86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids.ConclusionsWe detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants.

Project description:Necrotising enterocolitis (NEC) is a potentially serious illness with significant mortality and morbidity in preterm infants. Previous studies have reported association of volume and colour (bile and blood stained) of gastric residuals (GR) with NEC. We aimed to study this association in our cohort of extremely preterm (EP) infants. In a case-control study using retrospective data (January 2006-December 2011), EP (gestation < 28 weeks) infants with confirmed NEC ≥ stage II (cases) were compared with infants without NEC (controls) matched for birth weight (BW) and gestational age (GA). Forty cases of NEC ≥ stage II diagnosed at a median (IQR) age of 16.5 days (10.3-23) were compared with 40 controls matched for gestation (± 3 days) and birth weight (± 680 g). Median maximum GR volume (GRV) from birth to the day of occurrence of NEC was significantly higher in cases vs. controls (5.9 vs.3.7 ml; p < 0.001). Increased maximum GRV was associated with NEC ≥ Stage II in adjusted analysis (aOR 1.36, 95%CI 1.06-1.75, p = 0.017). There was no significant difference in GRV between cases and controls throughout the clinical course, including 72, 48 and 24 h before the onset of NEC. However, green (65.0% vs. 27.5%, p = 0.001) and haemorrhagic GRs (45.0% vs. 27.5%, p = 0.092) were higher 24 h before the diagnosis of NEC.Conclusion: GRV was not associated with NEC ≥ stage II. However, green and haemorrhagic GRs were significantly higher 24 h before the diagnosis of the illness. Adequately powered prospective studies are needed to confirm the significance of our findings. What is Known: •It is unclear whether large volume, dark-coloured and blood-stained GRs are associated with NEC. •The value of routine monitoring of gastric residuals in preterm infants is currently being questioned. What is New: •Volume of gastric residuals was not associated with significant NEC. •Green and haemorrhagic GRs were significantly higher 24 hours before diagnosis of NEC.

Dataset Information

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

Publications

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

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