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Embleton ND, Berrington JE, Dorling J, et al. Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials. Front Nutr. 2017;4:14doi: 10.3389/fnut.2017.00014.
Embleton, N. D., Berrington, J. E., Dorling, J., Ewer, A. K., Juszczak, E., Kirby, J. A., Lamb, C. A., Lanyon, C. V., McGuire, W., Probert, C. S., Rushton, S. P., Shirley, M. D., Stewart, C. J., & Cummings, S. P. (2017). Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials. Frontiers in nutrition, 414. https://doi.org/10.3389/fnut.2017.00014
Embleton, Nicholas D, et al. "Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials." Frontiers in nutrition vol. 4 (2017): 14. doi: https://doi.org/10.3389/fnut.2017.00014
Embleton ND, Berrington JE, Dorling J, Ewer AK, Juszczak E, Kirby JA, Lamb CA, Lanyon CV, McGuire W, Probert CS, Rushton SP, Shirley MD, Stewart CJ, Cummings SP. Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials. Front Nutr. 2017 May 08;4:14. doi: 10.3389/fnut.2017.00014. eCollection 2017. PMID: 28534028; PMCID: PMC5420562.
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Front Nutr. 2017 May 08;4:14. doi: 10.3389/fnut.2017.00014. eCollection 2017.

Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials.

Frontiers in nutrition

Nicholas D Embleton, Janet E Berrington, Jon Dorling, Andrew K Ewer, Edmund Juszczak, John A Kirby, Christopher A Lamb, Clare V Lanyon, William McGuire, Christopher S Probert, Stephen P Rushton, Mark D Shirley, Christopher J Stewart, Stephen P Cummings

Affiliations

  1. Newcastle Neonatal Service, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  2. Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
  3. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
  4. School of Medicine, University of Nottingham, Nottingham, UK.
  5. College of Medical and Dental Sciences, Institute of Metabolism and Systems Research, Birmingham University, Birmingham, UK.
  6. Clinical Trials Unit, University of Oxford, Oxford, UK.
  7. Department for Biomedical Sciences, School of Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
  8. Centre for Reviews and Dissemination, University of York, York, UK.
  9. Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
  10. School of Biology, Newcastle University, Newcastle upon Tyne, UK.
  11. Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
  12. School of Science and Engineering, Teesside University, Middlesbrough, UK.

PMID: 28534028 PMCID: PMC5420562 DOI: 10.3389/fnut.2017.00014

Abstract

Large randomized controlled trials (RCTs) in preterm infants offer unique opportunities for mechanistic evaluation of the risk factors leading to serious diseases, as well as the actions of interventions designed to prevent them. Necrotizing enterocolitis (NEC) a serious inflammatory gut condition and late-onset sepsis (LOS) are common feeding and nutrition-related problems that may cause death or serious long-term morbidity and are key outcomes in two current UK National Institutes for Health Research (NIHR) trials. Speed of increasing milk feeds trial (SIFT) randomized preterm infants to different rates of increases in milk feeds with a primary outcome of survival without disability at 2 years corrected age. Enteral lactoferrin in neonates (ELFIN) randomizes infants to supplemental enteral lactoferrin or placebo with a primary outcome of LOS. This is a protocol for the mechanisms affecting the gut of preterm infants in enteral feeding trials (MAGPIE) study and is funded by the UK NIHR Efficacy and Mechanistic Evaluation programme. MAGPIE will recruit ~480 preterm infants who were enrolled in SIFT or ELFIN. Participation in MAGPIE does not change the main trial protocols and uses non-invasive sampling of stool and urine, along with any residual resected gut tissue if infants required surgery. Trial interventions may involve effects on gut microbes, metabolites (e.g., short-chain fatty acids), and aspects of host immune function. Current hypotheses suggest that NEC and/or LOS are due to a dysregulated immune system in the context of gut dysbiosis, but mechanisms have not been systematically studied within large RCTs. Microbiomic analysis will use next-generation sequencing, and metabolites will be assessed by mass spectrometry to detect volatile organic and other compounds produced by microbes or the host. We will explore differences between disease cases and controls, as well as exploring the actions of trial interventions. Impacts of this research are multiple: translation of knowledge of mechanisms promoting gut health may explain outcomes or suggest alternate strategies to improve health. Results may identify new non-invasive diagnostic or monitoring techniques, preventative or treatment strategies for NEC or LOS, or provide data useful for risk stratification in future studies. Mechanistic evaluation might be especially informative where there are not clear effects on the primary outcome (ISRCTN 12554594).

Keywords: gut microbiota; lactoferrin; late-onset sepsis; mechanistic evaluation; metabolome; necrotizing enterocolitis; nutrition; preterm infant

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