Newcastle Neonatal Nutrition and NEC (N4) Research Group




Infants born prematurely are at higher risk of developing a disease of the intestine called necrotising enterocolitis (NEC). This disease occurs due to an inflammatory response, which is a defence mechanism of the baby, but when exaggerated results in parts of the intestine dying. The disease can have lasting consequences for the baby, including delayed neurological development. The disease is incredibly challenging for clinicians as infants may display a range of symptoms, or no obviously visible symptoms at all, and with no biomarkers for diagnosis there is no reliable way to present NEC onset.

While NEC is linked primarily to factors that cannot be controlled, such as the immaturity of the infant, it is also linked to potentially modifiable factors within the control of clinical care. The work of the Newcastle Neonatal Nutrition and NEC (N4) research group aims to better understand these latter aspects, with a particular focus on nutrition and the bacteria that live in the intestine of the preterm infant. Over the past decade the team have published over 50 peer-reviewed publications in this area and while our understanding of the disease is constantly evolving, I will now summarise our main findings.





Gut Microbiome

The gut is host to the largest bacterial community in the body and is also the largest immune organ, and in the newborn period is the main site experiencing rapid and dramatic interactions between host and microbes. In infants born full-term this process generally proceeds without difficulty, and a bacterial community – termed the microbiome - is established over the first weeks and months. In preterm infants, establishment of a stable gut bacterial community is more challenging and variable, with large day-to-day variation in bacteria within and between individuals. Collectively, the lack of bacterial diversity, lack of key bacteria associated with health in term infants (e.g. Bifidobacteria) and dominance by bacteria more often associated with disease (e.g. Klebsiella and Enterobacter) is associated with onset of NEC, as well as late onset sepsis. Such evidence begs the questions, would adding bacteria associated with health (e.g. Bifidobacteria) to preterm infants help protect them from disease. Such an intervention is called a ‘probiotic’ and an estimated 30% of UK neonatal intensive care units are currently trialling these. However, which exact bacteria should be given, how often, and in what concentration are important elements that are yet to be fully understood. Nonetheless, while more research is needed, there is promise for probiotics in improving preterm health.


Nutrition

Feeding a preterm baby is not trivial and the per kg calorific needs of the growing infant are similar to what an elite athlete would consume during endurance sport. This has to be managed alongside dangers of feeding the baby too much and overwhelming its gut and ability to process the nutrients. Owning to the numerous potential properties of breast milk, we are now intensively investigating several aspects of this natural biofluid to determine what factors might be most important in promoting infant health. We are further linking how these factors influence the developing gut microbiome. This represents relatively recent lines of investigation, but the early evidence is exciting. It’s not impossible to imagine taking a ‘probiotic’ one step further and also providing important nutrients that support the growth of baby and bacteria, ultimately providing short- and long-term benefit to the infant. Such a holistic therapeutic could be considered a ‘symbiotic’.


While much progress has been made, it is important to keep in mind that scientific research is a constant process of discovery and we are still learning. Of course, with grand challenges come great opportunities, and the N4 research group are driven to improve to lives of the youngest and most vulnerable humans.


You can find more detailed information, including publications and presentations at our website www.neonatalresearch.net


Dr Christopher Stewart

NEC UK Map Member and part of a multi-disciplinary, clinically focused, neonatal research team based in Newcastle, UK with collaborators across the UK, Europe and USA.


Areas of research focus on neonatal nutrition, necrotising enterocolitis (NEC), growth and long-term outcome, as well as exploring parental experiences of baby loss. Studies include large scale collaborative trials of feeding and nutrition, mechanistic studies focusing on the gut microbiome, transcriptome and metabolome, development of gut enteroid models, T-cell development, motor function, and long-term metabolic outcome using longitudinal cohort studies. Team members are based at Newcastle Hospitals NHS Foundation Trust, Northumbria University and Newcastle University.