“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.

How Early Biology Shapes Development

The first few years of life are a critical period for both brain development and the maturation of the immune system. Previous research has shown that epigenetics and the gut microbiome can each influence long-term health, but scientists have had limited understanding of how these two systems interact during early life.

“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.”

To investigate, the research team analyzed DNA methylation patterns, a common form of epigenetic modification, in umbilical cord blood from 571 infants. They combined those data with gut microbiome samples collected from 969 infants at 2, 6, and 12 months of age, along with microbiome samples from the infants’ parents during the third trimester of pregnancy.

When the children reached 36 months of age, researchers assessed their neurodevelopment using a behavioral questionnaire and looked for connections between developmental outcomes, gut microbes, and epigenetic patterns.

Factors That Influence the Infant Microbiome

The researchers found that several factors were associated with epigenetic patterns at birth, including delivery method, length of pregnancy, having older siblings, and maternal allergies. Interestingly, parental gut microbiomes did not appear to influence these birth-related epigenetic changes.

The development of the infant microbiome was linked to a different set of factors. Delivery method, antibiotic exposure, older siblings, and breastfeeding all played a role in shaping the community of microbes that developed during the first year of life.

Babies delivered by Caesarean section showed distinct DNA methylation patterns in several genes involved in immune function and brain development.

A Link Between Gene Regulation and Gut Bacteria

The study also revealed that epigenetic patterns present at birth affected how the gut microbiome evolved during infancy.

Infants who had higher levels of DNA methylation in certain immune-related genes tended to develop less diverse gut microbiomes by 12 months of age. These genes are involved in helping the body recognize and respond to pathogens.

The results suggest that biological signals present at birth may help guide the development of the gut microbial community during a child’s first year.

Gut Microbes and Neurodevelopmental Risk

When researchers examined behavioral outcomes at age three, they found that signs of ASD and ADHD were associated with specific combinations of epigenetic markers and gut microbes.

However, the findings also pointed to a potentially protective role for certain bacteria. Children who carried epigenetic patterns associated with ASD were less likely to show signs of the condition if they acquired Lachnospira pectinoschiza during infancy. Similarly, children with epigenetic patterns associated with ADHD appeared less likely to show signs of the disorder if they acquired Parabacteroides distasonis 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.”

Future Possibilities for Probiotics and Brain Health

The researchers are continuing to follow the participating children to better understand how early-life epigenetic patterns and microbiome development influence health later in childhood. They emphasize that laboratory studies will be needed to confirm the observed relationships between gut bacteria 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.

The study was supported by InnoHK, the Government of Hong Kong, the D. H. Chen Foundation, and the New Cornerstone Science Foundation.