Modulating the gut microbiome in low birthweight (LBW) infants to prevent neonatal sepsis and anti-microbial resistance

Abnormal gut bacterial colonisation in LBW infants nursed in hospital contributes to neonatal sepsis. Exposure to multiple antibiotics likely drives antimicrobial resistance (AMR) in the gut flora.  We will describe the progression of gut bacterial colonisation and AMR development from birth and assess whether resistance against gut pathogens may occur with nutritional interventions such as pre/probiotics and lactoferrin.

Where does this project lie in the translational pathway? 

T1 – Basic Research in Medecine

T2 Human / Clinical Research in Medecine

 

 

T1 + T2. The project would link basic research that describes gut bacterial colonisation and development of AMR in neonatal units in a low resource setting, environmental factors associated with abnormal colonisation / AMR and undertake pilot studies of one or more nutritional interventions, such as pre/probiotics and lactoferrin, on gut microbiome development and clinical outcomes.

What are the methodological aspects (including quantitative skills training elements if appropriate) of the PhD project?

Omics: Analysis of neonatal gut microbiome including effect of antibiotic exposure

Critical analysis: Determining the evidence for specific nutritional interventions in colonisation resistance

Quantitative: design and analyse pilot study re effects of interventions on bacterial colonisation and health outcomes

What are the expected outputs (publications, funding, and impact) of the PhD project?

Publications would a) review the evidence for nutritional interventions in modulating the development of the gut microbiome in newborns and b) describe bacterial colonisation of the newborn gut in preterm/low-birth weight infants in neonatal units in sub-Saharan Africa and the risk factors for colonisation by potential pathogens and AMR (e.g. mode of delivery, antibiotic exposure). Preliminary data regarding the potential of nutritional interventions to reduce gut colonisation with Gram negative bacteria/potential pathogens and AMR organisms would inform the design of a larger clinical trial. This project would be hosted by the neonatal network established in Nigeria and Kenya through the “Improving the survival, growth and development of low birth weight newborns through better nutrition” project funded by an MRC Confidence in Global Nutrition and Health Research in Medecine Institutional pump-priming award.

What external industry links or training opportunities will be available. (ex. SMEs, industry, health agencies)?

Clinical research would be based at the Neonatal Unit and supported by the WHO Reference Laboratory, University College Hospital, Ibadan, Nigeria where highly abnormal bacterial colonisation of the newborn gut has recently been described. We have an existing academic collaboration with Dr. Sue Plummer, Cultech Ltd, Newport, UK () who has provided us with probiotics for research previously and has agreed to support this study and to host a student to evaluate probiotic organisms in gut model studies. We also have existing academic collaborations with other probiotic manufacturers/suppliers who undertake research: Mead Johnson Nutrition () and Nutricia (). Mead Johnson Nutrition has also supplied us previously with products free-of-charge for clinical trials. We would explore secondments to these partners and secondment to a UK laboratory to learn advanced molecular analysis of the gut microbiome as part of a comprehensive training programme.

 

 

Required skills/experience/aptitudes

Students will need to be able to develop skills across several research disciplines including critical appraisal, laboratory-based research and supporting clinical trials. Willingness to work in both clinical and laboratory settings and with a range of different health professional cadres and in sub-Saharan Africa would be required.

Key publications that relate to this project

1.

McMIllan, A.E. Orimadegun, M.W. Sumarah, J. Renaud, M. Muc, G.B. Gloor, O.O. Akinyinka, G. Reid, S.J. Allen. Metabolic derangements identified through untargeted metabolomics in a cross-sectional study of Nigerian children with severe acute malnutrition. Metabolomics 2017;13:1-14. DOI: 10.1007/s11306-016-1150-2.

2.

Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, Dhar A, Brown H, Foden A, Gravenor MB, Mack D. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated and Clostridium difficile diarrhoea in older in-patients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2013; 382:1249-57.

3.

Allen SJ, Jordan S, Storey M, Thornton CA, Gravenor MB, Garaiova I, Jones RH, Macfarlane TV, Seager AL, Manshian B, Moller M, Plummer SF, Wang D, Morgan G. Probiotics in the prevention of eczema: a randomised, placebo-controlled clinical trial. Arch Dis Child 2014; 99:1014–1019.

4.

Allen S. The Potential of Probiotics to Prevent Clostridium difficile Infection. Infectious Disease Clinics of North America 2015; Vol 29, Issue 1, pp. 135-144.

5.

Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database of Systematic Reviews 2010; 11:CD003048.

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