The Pregnancy & Early Life Study

Summary

Participation Requirements

Description

The gut is home to a diverse and dynamic microbial ecosystem, termed the microbiota. These microbes provide their host with various beneficial effects including acquisition of additional nutrients and energy from dietary components, optimal development of the immune system, and resistance against in...

The gut is home to a diverse and dynamic microbial ecosystem, termed the microbiota. These microbes provide their host with various beneficial effects including acquisition of additional nutrients and energy from dietary components, optimal development of the immune system, and resistance against invading pathogenic microbes, and are thus critical for health. As the neonatal gut is essentially sterile at the outset, these beneficial microbes and their associated functions are acquired after initial colonisation by pioneer bacteria, successive diversification, and changes in microbial population densities until a climax or 'stable' microbiota has established during infancy and early childhood. The majority of human physiological functions are programmed either in utero, i.e. during pregnancy, or during the early-life window. Thus, the investigators need to determine early-life microbiome profiles over this critical period, particularly what factors influence these microbial signatures, and how changes in the signature are correlated with healthy development during this time-period. It is proposed that the initial colonisation and establishment of the gut microbiome during early life is closely linked with the promotion of healthy development. Critically, disturbances within this pioneering microbial community (both in mother and baby) have the potential to increase the risk of developing diseases such as autoimmune conditions, allergic-type disorders, infections and chronic intestinal diseases; disturbance may be caused by antibiotics, dietary changes (i.e. breast versus formula milk) and even the way the baby is delivered (i.e. Caesarean section versus vaginal). The proposed transmission of microbial species from the maternal microbiome to the baby is a key feature of birth, with subsequent waves of colonisation occurring as the baby gets older. There is also an increasing awareness of the importance of maternal health during pregnancy (as affected by obesity and antibiotic use) for the baby's development and health, both before and after birth. Importantly, these life stage events appear to be governed by particular interactions (immune and dietary) that 'select' beneficial microbes such as Bifidobacterium species; species in this genus are prevalent in the gut and vagina of mothers in the later stages of pregnancy and can represent up to 80% of the total microbiome in healthy infants. These pioneering microbe species seem to be important for the development of a healthy microbial community and the subsequent formation of a more 'adult-like' microbiome by the time the child has reached 2-3 years of age; this is thought to be in response to an expanding nutritional environment, i.e. from a milk-based diet to a more complex diet at weaning. Although several studies have tried to probe these key questions, there are currently many unknowns with respect to this key developmental window including (i) how does the microbiome change in response to different phases of pregnancy across different body sites (and how does this correlate with routinely collected clinical information), (ii) are microbes from mothers directly passed to infants during birth (and how does birth mode affect this i.e. vaginal vs. C-section), (iii) how do factors like diet and antibiotics influence the maternal microbiome, and what is the impact on developing infant microbial communities, (iv) how do different feeding regiments (e.g. breast vs. formula milk) influence specific microbial populations in the infant (e.g. Bifidobacterium), (v) how do these microbes influence immune and metabolic health, and how does this correlate with clinical information captured both in mother and baby over time, and (iv) if the investigators carry out in-depth mechanistic studies using in vitro and in vivo models, can the investigators determine how specific microbes and communities contribute to healthy development and prevent disease incidence? Critically, if the investigators are to determine the importance of the early life microbiome, the investigators must set-up and carry out comprehensive longitudinal pregnancy and infant studies, i.e. PEARL, to address these key points. Moreover, gathering these data is critical for implementation of new therapies and health-associated practices that would be expected to have beneficial effects, both in the short-term and across the life course, which could be explored in subsequent studies after PEARL. The PEARL Study will build on the Chief Investigator's (Hall) ongoing BAMBI Study - Baby Associated Microbiota of the Intestine (University of East Anglia Faculty of Medical Health Research Ethics Committee Reference 2012/2013 - 42 HT), which is collecting faecal samples from preterm infants residing in Neonatal Intensive Care Units (NICUs) and following these babies after they are discharged home for up to 3 years of age. This study has been analysing microbiome signatures in these preterm infants and correlating these to external factors such as antibiotic usage and diet and also immune markers.

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