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The first 1000 days of life—from conception to two years—is considered the most crucial period for the development of a child. But how crucial is this period for the development of a child’s gut microbiome and their likelihood of developing a disease that could affect the rest of their life?
The Child Health Research Unit Barwon Health (CHRU) is determined to find out.
CHRU say the origins of diseases such as diabetes, obesity, cardiovascular disease, allergy, asthma, autism, ADHD, anxiety and depression may be traced back to pregnancy and early childhood.
They aim to discover ways to prevent these diseases in the first 1000 days of life and improve the health outcomes for all children as well as ultimately relieve the burden on the public health system.
The CHRU builds on the legacy of late Associate Professor Peter Hewson, who was a Geelong paediatrician who led seminal studies regarding the burden of developmental problems in children and the genetics of Autism. The current research lead Professor Peter Vuillermin established the Barwon Asthma Study in 2007 and the internationally recognised Barwon Infant Study (BIS) in 2010. BIS is a birth cohort study in collaboration with Barwon Health and the Murdoch Children’s Research Institute (MCRI).
This landmark study follows more than 1000 Geelong mothers and their children and has already collected more than 500,000 biological samples, in what they say is one of the most complete early life “biobanks” in the world.
This wealth of data is now being used to identify new prevention strategies to improve the health outcomes of children across the board.
“We’ve been intrigued and concerned by the increase in non-communicable diseases in kids. The conditions have increased dramatically in the modern environment include allergy, asthma, type 1 diabetes and, neurodevelopmental disorders such as autism and ADHD,” Prof Vuillermin says.
“We understand relatively little of the biological ballet that plays out in pregnancy and into infancy, and which in a traditional environment, results in the baby’s immune system being both robust and well regulated. We want to understand what drives dysregulation of this process leading to disease. Our goal is to understand how the process is meant to work, how it goes wrong, and how to use that knowledge to inform prevention strategies.”
BIS has found a link between the maternal and infant gut microbiome and an infant’s risk of developing food allergy. The team discovered that the presence of the bacteria Prevotella in a mother’s gut during pregnancy is strongly associated with protection against allergic disease in the baby.
It has also found children with the bacteria Prevotella in their gut at 12 months of age had a lower prevalence of anxiety-like behaviours, including shyness, sadness and an internal focus, an indicator they may be at higher risk of going on to develop childhood anxiety.
“It’s hard to know where the microbiome field will end up, but I think what we can confidently say is that a diet high in vegetables and legumes and minimising unnecessary use of antibiotics are likely to be beneficial, and some of these benefits may be mediated by the microbiome”,
Prof Peter Vuillermin
In addition to the Barwon Infant Study, CHRU is also conducting other research: the Environmental Determinants of Islet Autoimmunity (ENDIA) Study—an NHMRC-funded longitudinal observational study of 1500 babies across Australia who have a first-degree relative with type 1 diabetes;and, the OM85 trial, which is investigating whether the immune modulator OM85 can prevent hospital admission due to asthma among preschool-aged children.
The CHRU is heading up this multicentre clinical trial that involves more than 40 hospitals around Australia and New Zealand, which are part of the Children’s Inpatient Research Collaboration of Australia and New Zealand (CIRCAN). The study was awarded in 2019 a highly competitive $1.6 million grant from the National Health and Medical Research Council to conduct the Assessing OM85 for Reduction of Hospital Admissions due to Preschool Wheeze (ARROW) trial
Prof Vuillermin says the aim is to recruit 2000 preschool-aged children with asthma or what some may call “preschool wheeze”.
“We’re trialling a medication called OM85, which is a mixture of 21 different killed bacteria,” Prof Vuillermin says.
“The children take OM85 once a day for the first day of the month. In the experimental models, OM85 stimulates the immune system so that the child has a more effective response to viral infections and also mounts a more effective regulatory immune response.
“Which is the opposite to what happens to kids with asthma. They get a cold, they fail to mount an early and effective response, it goes to their chest, and they end up with excessive inflammation that causes swelling and airflow obstruction.
“Preschool wheeze is the most common reason that children are admitted to hospital in many parts of the world and there are no effective prevention strategies at the moment. If the the CIRCAN ARROW trial demonstrates OM86 reduces hospital admissions, then that would be game-changing.”
CHRU has two more significant studies in the pipeline. One of which is the Pregnancy Research and Translation ecosystem (PRT-E) study, which was recently awarded the inaugural Western Alliance Flagship Research Program funding of $198,969.
PRT-E aims to use research data to improve maternal and infant outcomes, such as reducing the high rate of births by caesarean section, which is now around 40 per cent.
The study will leverage pregnancy care data from the Birthing Outcomes System (BOS) and data from the GenV initiative, which plans to recruit and follow 80 per cent of infants born in Victoria over the next two years.
“We’re also going to form a pregnancy stakeholder working group, which will comprise of obstetricians, midwives and consumers from the participating health centres,” Prof Vuillermin says. “And that group will meet regularly to co-produce the research agenda and program.”
The second study will be the Barwon Resilience and Vulnerability (BRaVe) cohort study that will specifically look at mothers and infants who come from disadvantaged backgrounds.
“We have pockets of disadvantage in our region that are as extreme as anywhere in Australia – communities in which 40 per cent of kids are starting school with a developmental disorder,”
Prof Peter Vuillermin
“Early life development plays a major role in the ongoing cycle of disadvantage because if you are struggling at school, that affects your whole life trajectory. In BIS, like most cohort studies, we have an under-representation of disadvantaged families. BRaVe is designed to address this under-representation and seek to replicate some of the findings we had in BIS.”
CHRU is a relatively small group of researchers made up of 11 core members—but their impact is proving large.
“When it’s all said and done, the only performance indicator in medical research that stands the test of time is discoveries that make a difference,” Prof Vuillermin says.
“We would love to be a part of a journey where we go from discovery to the development and evaluation of an intervention, to the implementation, translation of evidence of a population effect. Something like the Gardasil vaccine, or the discovery of the rotavirus and then development of the rotavirus vaccine, or the discovery of the role of Helicobacter pylori and the interventions and public health outcomes that have come out of that.
“There’s no reason why the Barwon Health and Deakin University Partnership can’t do that – make important discoveries, and go the full journey to improved public health.”
