CU Medicine reveals the interplay between epigenetic changes and gut microbiome in newborns
A research team from CU Medicine is the first to reveal the interplay between epigenetics and gut microbiome in newborns significantly associated with child’s neurodevelopmental outcomes.The team will continue to explore the association between gut microbiome and neurodevelopment, with the aim of developing safe, non-invasive early interventions to help the children nurture a healthy gut microbiome and reduce related challenges.
(From left) Professor Lin Zhang, Assistant Professor from Department of Anaesthesia and Intensive Care at CU Medicine; Professor Siew Ng, Croucher Professor in Medical Sciences at CU Medicine, Director of the Microbiota I-Center (MagIC) and New Cornerstone Investigator; Professor Francis Chan, Choh-Ming Li Professor of Medicine and Therapeutics at CUHK, Director of the Centre for Gut Microbiota Research at CU Medicine and Co-Director of MagIC; Professor Hein Min Tun, Associate Professor of the Jockey Club School of Public Health and Primary Care at CU Medicine and Associate Director of MagIC; and Professor Ye Peng, Research Assistant Professor from The Jockey Club School of Public Health and Primary Care at CU Medicine
Infants’ epigenomes and microbiomes are intertwined with immune and neurodevelopmental processes, affecting their risk of developing neurodevelopmental disorders. A multidisciplinary research team from The Chinese University of Hong Kong’s Faculty of Medicine (CU Medicine) has revealed that epigenetic changes present at birth can impact how an infant’s gut microbiome develops during their first year. They have also identified specific epigenetic changes and gut microbes that are associated with signs of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) when the children are three years old. Caesarean section was also identified as a contributing factor. The team believes that probiotics or live biotherapeutics could potentially reduce the risk of neurodevelopmental challenges, and will conduct further studies to see how these early-life factors relate to children’s health as they grow. The findings of this research have been published in Cell Press Blue, a leading academic journal under Cell Press.
The first years of life are critical for brain development and immune system maturation. Though previous studies have shown that both early epigenetic changes and gut microbiome development can impact health in later life, little is known about how these two systems interact. Unlike the stable human genome, epigenetic changes act as a molecular switch that can be altered by various stimuli before and after birth. Without changing the DNA sequence, these changes, such as DNA methylation, influence how genes are expressed and may therefore affect the health of young children.
Epigenetics impact microbiome development in first year
The CU Medicine team recruited 969 families for a longitudinal birth cohort study to assess how early-life exposure can influence the gut microbiome. The researchers characterised DNA methylation patterns from the umbilical cord blood of 571 infants. They paired this information with gut microbiome data collected from infants at birth and two, six and 12 months of age, and from their parents during the third trimester of pregnancy.
They found that an infant’s epigenome at birth was associated with birth mode, length of gestation, having older siblings and maternal allergies but was not affected by their parents’ gut microbiomes. Microbiome development, on the other hand, was associated with birth mode, antibiotics, having older siblings and breastfeeding. The team also showed that an infant’s epigenome at birth impacted how their microbiome developed during their first year. Specifically, infants developed less diverse gut microbiomes at six months of age when they showed higher rates of DNA methylation in immune genes involved in recognising pathogens.
A research team from CU Medicine conducted a birth cohort study and found hypermethylation of neurogenic genes is linked to higher ASD and ADHD scores at age 3, while C-section is associated with altered DNA methylation and changes in vertical microbiome transmission. However, the team believes colonisation of specific gut microbes can mediate or modulate these epigenetic risks.
The results of the study reveal that infants who were born by Caesarean section show different patterns of DNA methylation for several genes involved in immune responses and brain development, possibly reflecting lack of exposure to labour stress and cortisol. Caesarean section also reduced vertical maternal microbiome transmission, with the paternal microbiome partially compensating.
Other microbial species mitigate ASD and ADHD risk
When the children reached 36 months of age, the researchers used a behavioural questionnaire to assess their neurodevelopment and investigate links between the microbiome, epigenome and early signs of ASD and ADHD. The behavioural survey revealed that those signs of ASD and ADHD in three-year-olds were associated with specific epigenetic patterns and the presence of certain gut microbes. Some of these epigenetic DNA methylation regions are associated with neurodevelopment in infants and young children, and are also consistent with symptoms of ASD and ADHD. However, other microbial species seemed to mitigate these effects: infants with epigenetic patterns associated with ASD or ADHD were less likely to show signs of the disorders if they acquired Lachnospira pectinoschiza and Parabacteroides distasonis, respectively, during their first year. These findings demonstrate the interrelationship between epigenetics, the microbiome and neurodevelopment.
Senior author of the study Professor Francis Chan Ka-leung, Choh-Ming Li Professor of Medicine and Therapeutics at CUHK, Director of the Centre for Gut Microbiota Research at CU Medicine and Co-Director of the Microbiota I-Center (MagIC), said: “Certain bacteria seem to offer protection, which is exciting because it suggests there could be ways to support a child’s development through diet or probiotics in the future.”
Co-senior author of the study Professor Tun Hein-min, Associate Professor of the Jockey Club School of Public Health and Primary Care at CU Medicine and Associate Director of MagIC, added: “We wanted to see how the epigenome and microbiome interact in early life and if their interaction could influence a child’s risk of developing neurodevelopmental conditions like ASD and ADHD. We discovered a kind of conversation happening: a baby’s epigenetic setting at birth can influence their risk of neurodevelopmental disorders but the presence of certain ‘good’ bacteria in their gut can step in and modify the risk.
“The foundations for brain health are laid very early, even before birth. However, we don’t want people to think this means a child’s developmental path is fixed at birth. These are complex conditions with many causes, and we’ve only uncovered a small piece of a very large puzzle.” The researchers are continuing to follow the children who participated in the study to see how these early-life factors relate to their health as they grow. They note that laboratory experiments are needed to confirm the associations between gut microbes and neurodevelopment.
First author of the study Professor Ng Siew-chien, Croucher Professor in Medical Sciences at CU Medicine, Director of MagIC and New Cornerstone Investigator, concluded: “The ultimate goal is to develop safe, non-intrusive early interventions such as specific probiotics or live biotherapeutics that can help nurture a healthy gut microbiome and potentially reduce the risk of neurodevelopmental challenges.”
