Infant Gut Bacteria May Influence Autism and ADHD Risk, Study Suggests

Scientists report new evidence that gut bacteria in early life may be linked to a child’s risk of autism spectrum disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD). The research connects epigenetic changes present at birth with the development of the infant microbiome and neurodevelopmental traits by age three.

The study, published in Cell Host & Microbe, followed babies in Hong Kong from birth through early childhood. The findings suggest that specific microbes could potentially have a protective role in neurodevelopment among children who already show biological risk markers at birth.

Epigenetics, microbiome and the infant brain

Epigenetics refers to chemical modifications, including DNA methylation, that affect how genes are switched on or off without changing the underlying DNA sequence. These patterns can be influenced by pregnancy conditions, birth events and other early-life exposures.

The gut microbiome is the diverse community of bacteria, viruses and fungi that colonize the intestine. During the first year of life, this ecosystem develops rapidly and interacts with the immune system and the so-called gut–brain axis.

Previous research has shown that both epigenetic processes and the microbiome are connected with immunity, metabolism and brain function. However, researchers have had limited information about how these systems interact during the critical developmental period from birth through toddlerhood.

Large birth cohort in Hong Kong

The study drew on a prospective birth cohort involving hundreds of families at The Chinese University of Hong Kong. Researchers examined umbilical cord blood from 571 infants to map DNA methylation patterns present at birth.

They also collected stool samples from 969 infants at 2, 6 and 12 months to profile gut bacteria, alongside samples from parents during late pregnancy. At 36 months, the children’s behavior and development were evaluated using standardized questionnaires.

The researchers examined relationships between epigenetic markers, microbiome composition and early traits associated with ASD and ADHD. Because clinical diagnoses at age three are relatively uncommon, the study focused on behavioral characteristics that can indicate elevated neurodevelopmental risk.

Birth factors shaping early biology

Cesarean delivery, gestational length, having older siblings and maternal allergies were associated with distinct DNA methylation patterns at birth. These patterns frequently involved genes connected with immune responses and neural development.

For example, babies delivered by cesarean section showed altered methylation in genes involved in inflammation and brain signaling. The researchers considered differences in birth stress, hormone exposure and early microbial contact during delivery as possible factors behind these patterns.

Development of the microbiome during the first 12 months, meanwhile, was strongly associated with delivery mode, antibiotic use, breastfeeding and household composition. Breastfed infants generally developed more stable microbial communities.

How gene regulation relates to microbes

The researchers found that epigenetic patterns present at birth were associated with how the gut microbiome developed during the first year. Infants with higher methylation in certain immune-related genes tended to have lower gut bacterial diversity by 12 months.

Microbial diversity is often considered an indicator of microbiome resilience, although greater diversity is not necessarily beneficial in every context. The findings suggest a connection between immune-related gene regulation established around birth and the microbes that subsequently colonize the infant gut.

These interactions may form part of a broader relationship in which early gene regulation, microbial development and signals involving the immune system and brain interact during sensitive stages of development.

Protective role for specific bacteria

When researchers incorporated behavioral data collected at age three, they identified combinations of epigenetic markers and bacterial species associated with ASD- and ADHD-related traits. Some bacterial species were associated with lower rather than higher levels of these traits.

Children whose birth epigenetic signatures were associated with ASD risk showed fewer ASD-like behaviors when Lachnospira pectinoschiza was present in their gut microbiome during infancy. This bacterium belongs to a group known for producing short-chain fatty acids.

Similarly, Parabacteroides distasonis was associated with a lower likelihood of ADHD-like traits among children whose epigenetic profiles were associated with ADHD. Both species may be involved in processes related to inflammation, gut barrier function and signaling between the gut and other parts of the body.

Caution, complexity and next steps

The researchers emphasize that ASD and ADHD involve numerous genetic and environmental factors, with the microbiome representing only one potential part of a much larger biological picture. Associations between particular bacteria and behavioral traits do not establish that the microbes directly caused or prevented those outcomes.

Behavioral screening at age three also cannot substitute for a full clinical diagnosis. Further research, including animal studies and longer-term follow-up of the children, will be needed to determine whether the identified bacteria directly influence neurodevelopment.

Researchers also want to investigate which dietary and environmental factors encourage colonization by potentially beneficial microbes. Such work could eventually help determine whether modifying the early-life microbiome has practical applications.

The findings raise the possibility that early childhood could provide a window for future non-invasive interventions. Targeted probiotics, prebiotics or live biotherapeutics could potentially be investigated as ways of supporting neurodevelopment in children considered at higher risk, although such approaches would require further research and clinical testing.

The study was funded by InnoHK, the Government of Hong Kong, the D. H. Chen Foundation and the New Cornerstone Science Foundation. It adds to research examining how maternal health, birth circumstances, infant nutrition, epigenetic regulation and the developing microbiome may interact during early childhood.