Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03916874 |
| Other study ID # |
QIB02/2018 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2019 |
| Est. completion date |
December 1, 2024 |
Study information
| Verified date |
November 2023 |
| Source |
Quadram Institute Bioscience |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The gut is home to a diverse and dynamic microbial community, termed the microbiota. The
microbiota is essential for health and wellbeing and is involved in acquisition of nutrients
and energy from the diet, optimisation of the immune system, and resistance against invading
pathogens. Critically, in both new mothers and their babies, any disturbance of the
microbiota (caused, for example, by antibiotics, delivery mode [vaginal/Caesarean section],
or dietary change), has the potential to increase the risk that the baby might subsequently
develop allergic-type disorders, infections, and chronic intestinal diseases.
Early life is a key period of development, but the investigators need a clearer understanding
of how maternal factors and transmission of beneficial microbes from mother to baby influence
the development of a healthy infant microbiota. This is only possible through longitudinal
studies, where the profiles of microbiota from cohorts of mothers and their babies are
correlated with routine and more specific clinical data (i.e. antibiotics and diet)
throughout pregnancy and into early life.
In order to achieve the aims of the study, the Quadram Institute Bioscience (QIB) will work
in collaboration with the Norfolk & Norwich University Hospital (NNUH) to recruit 250
pregnant female participants. Study duration will be approximately 31 months and during this
time, the investigators will ask the participants to collect urine and stool samples and low
vaginal and skin swabs. Blood samples and breast milk are optional. From her newborn,
investigators will ask the participant to collect a meconium and stool samples and skin
swabs. The participant will complete three different types of questionnaires for herself and
her newborn over 31 months. This study is fully funded by the Biotechnology and Biological
Sciences Research Council (BBSRC).
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 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.
