PhD project title

Maximizing the Clinical Impact of Human milk on Prevention of Necrotizing Enterocolitis

Outline description, including interdisciplinary, intersectoral and international dimensions (300 words max)

Human milk (HM) is a complex biofluid that has evolved to contain thousands of bioactives to develop the new-borns’ immature immunity. Although benefits of breastfeeding are numerous to both mother and child, one of the most well-defined benefits is in the reduction in risk of NEC – a condition where the gut becomes inflamed and perforates. For babies born before 30 weeks of gestation, the risk of developing NEC is 20 times higher if they are formula rather than breastfed. How exactly this is mediated is, however, not well defined. This project will take an interdisciplinary approach combining the microbiology and metabolomics (Cameron) and proteomics (Collins) expertise of the supervisory team to develop a systems biology view of host-pathogen interactions. Through the utilisation of samples collected as part of a longitudinal cohort organised by the Human Milk Foundation, an in vitro system will be used to model how different components of HM interact with key NEC pathogens. Human milk samples will be fractionated and treated to separate biomolecules of different chemical classes and incubated with single and multi-species communities associated with the new-born gut microbiome. Metabolomic and proteomic analysis will be used to identify key mediators of host-pathogen interactions which will then be carried forward for further analysis to identify whether they act in isolation or unison with other HM bioactives. As donor HM is frequently the source of feeding for new-borns at risk of NEC, this project will also take an intersectoral approach through partnership with the Hearts Milk Bank (run by the Human Milk Foundation) to understand how routine processing and storing of donor HM may affect bioactives molecules associated with NEC suppression. Comparison against international milk bank practices will also be undertaken to establish potential best practice methods for preserving HM bioactives for management of NEC risk.

This project has many international elements, as a primary result of the global decline in breastfeeding rates. This project will address the issue of NEC and how it can be better understood to improve treatment outcomes for prematurely born infants. This would have a global impact. The work would be of considerable interest to the international human milk and infant feeding scientific communities and would be presented at the International Society for Research in Human Milk and Lactation bi-annual conference and published in international journals.

Key words/descriptors

Microbiome / human milk / breastfeeding / microbiology / metabolomics / proteomics

Fit to CITI-GENS theme(s)

• Information Technology, - this project will utilise large and complex datasets and will require advanced information processing techniques which will utilise the ‘Kelvin’ research cluster.
• Advanced Manufacturing, - this project will explore the processing of donor human milk and provide novel information to improve techniques. As a result of its exploration of disease prevention mechanisms, there is further potential to provide novel therapeutic targets for gastrointestinal infections.
• Life Sciences, - Northern Ireland has the lowest breastfeeding rates in the UK. This project will provide novel information on the protective benefits of human milk and may aid in public health messaging and clinical practice.
• Creative Industries.

Supervisor Information

First Supervisor: Simon Cameron                                                                       School: School of Biological Sciences

Second Supervisor: Ben Collins                                                                          School: School of Biological Sciences

Third Supervisor: Natalie Shenker                                                                     Company: Human Milk Foundation

Name of non-HEI partner(s)

Human Milk Foundation – Dr Natalie Shenker

Contribution of non-HEI partner(s) to the project:

The non-HEI partner (Human Milk Foundation represented by Dr Natalie Shenker) will provide support to the Fellow through expertise in human milk banking, clinical applications of human milk, and access to samples collected as part of a longitudinal cohort. Based at the Rothamsted Institute, the Fellow will be able to undertake a placement at the Hearts Milk Bank (which is operated by the Human Milk Foundation) where they will receive training in processing of donor human milk and be able to conduct onsite analysis of unprocessed milk.

The Human Milk Foundation was founded in 2017 and works to maximise the number of families who feed their babies with human milk. Through the Hearts Milk Bank, they provide screened donor milk to sick, premature babies in NICUs, and to mothers with cancer and other conditions. This project will be an extension of the ongoing research collaboration between the First Supervisor and the Human Milk Foundation / Hearts Milk Bank.

The Human Milk Foundation is the UK’s only foundation that supports research into human milk and lactation. Natalie Shenker is one of the Directors of the HMF and will provide support to the project through advice on clinical implications of findings, and through the provision of donor human milk samples through the Hearts Milk Bank. Although the non-academic supervisor is not based in Northern Ireland, they will join at least three meetings per year either in-person or remotely and the Hearts Milk Bank will provide a placement for the project of at least one week in their facility at the Rothamsted Research campus. Although Natalie Shenker is a UKRI Fellow at Imperial College London, this is a part-time appointment and her involvement in this project will be in a purely non-academic capacity through the Human Milk Foundation.

Faculty

Faculty of Medicine, Health, and Life Sciences

Research centre / School

Institute for Global Food Security / School of Biological Sciences / School of Pharmacy

Subject area

Microbiology