The gut microbiome and epigenetics—molecular switches that turn genes on or off—are intertwined, and both contribute to neurodevelopment, finds a study publishing April 10 in the Cell Press journal Cell Press Blue. The researchers showed that epigenetic changes present at birth can impact how an infant's gut microbiome develops during their first year. They also identified specific epigenetic changes and gut microbes that were associated with signs of autism spectrum disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) when the children were three years old.
"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," says senior author and gastroenterologist Francis Ka Leung Chan of The Chinese University of Hong Kong.
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.
"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," says co-senior author and public health researcher Hein Min Tun of The Chinese University of Hong Kong. "We discovered a kind of conversation happening: a baby's epigenetic setting at birth can influence their risk for neurodevelopmental disorders, but the presence of certain 'good' bacteria in their gut can step in and modify the risk."
The researchers characterized DNA methylation patterns—a type of epigenetic change—from the umbilical cord blood of 571 infants. They paired this information with gut microbiome data collected from 969 infants at 2, 6, and 12 months of age, and from their parents during the third trimester of pregnancy. When the children reached 36 months of age, the researchers used a behavioral questionnaire to assess their neurodevelopment and investigate links between the microbiome, epigenome, and early signs of ASD and ADHD.
They found that an infant's epigenome at birth was associated with birth mode, length of gestation, having older siblings, and maternal allergies, but it 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. Infants who were born by Caesarean section showed different patterns of DNA methylation for several genes involved in immune responses and brain development.
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 12 months of age when they showed higher rates of DNA methylation in immune genes involved in recognizing pathogens.
The behavioral survey revealed that signs of ASD and ADHD in 3-year-olds were associated with specific epigenetic patterns and the presence of certain gut microbes. 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.
"The foundations for brain health are laid very early, even before birth," says Tun. "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.
"The ultimate goal is to develop safe, non-intrusive early interventions such as specific probiotics or live biotherapeutics, that could help nurture a healthy gut microbiome and potentially reduce the risk of neurodevelopmental challenges," says first author and gastroenterologist Siew Chien Ng of The Chinese University of Hong Kong.
