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Gut microbes linked to early brain risks

Scientists have identified a link between biological changes present at birth, the development of gut bacteria during infancy and early signs of autism spectrum disorder and attention-deficit/hyperactivity disorder by age three, raising fresh questions about how brain development may be shaped before and after delivery.

A large birth-cohort study led by researchers at The Chinese University of Hong Kong’s Faculty of Medicine found that epigenetic marks in umbilical cord blood appeared to influence how a baby’s gut microbiome developed during the first year of life. Certain gut microbes were also associated with a reduced likelihood of early behavioural signs linked to autism spectrum disorder and ADHD among children carrying particular epigenetic patterns.

The findings do not show that gut bacteria prevent autism or ADHD, nor do they establish a direct cause. Researchers said the results point instead to a complex interaction involving genes, early environmental exposure, immune development and microbial colonisation. The work adds to growing evidence that the gut-brain axis may play a role in neurodevelopment, while underlining the need for laboratory studies and longer follow-up before any treatment claims can be made.

The research team recruited 969 families and examined DNA methylation, a form of epigenetic regulation that can influence whether genes are switched on or off without altering the underlying DNA sequence. Umbilical cord blood from 571 infants was analysed for methylation patterns, while gut microbiome samples were collected from babies during the first year of life and from parents during the third trimester of pregnancy.

The study found that an infant’s epigenome at birth was associated with delivery mode, gestational length, older siblings and maternal allergies. Gut microbiome development was linked to delivery mode, antibiotic exposure, older siblings and breastfeeding. Babies with higher methylation in immune genes involved in recognising pathogens had less diverse gut microbiomes at six months, suggesting that immune-related biological programming at birth may affect microbial development.

Caesarean delivery emerged as a notable factor. Babies born by Caesarean section showed different methylation patterns in genes linked to immune responses and brain development, and they had reduced transfer of maternal microbes. Paternal microbiome contribution appeared to partially compensate, reflecting the wider household role in early microbial colonisation.

When children reached 36 months, researchers assessed early signs associated with autism spectrum disorder and ADHD through behavioural questionnaires. The analysis found that higher scores were associated with specific epigenetic patterns and the presence or absence of certain gut bacteria. Infants with epigenetic patterns linked to autism signs were less likely to show those signs if they had acquired Lachnospira pectinoschiza during their first year. A similar pattern was observed for Parabacteroides distasonis and ADHD-related signs.

Francis Chan Ka-leung, senior author of the study and a leading gastroenterology researcher at CU Medicine, said certain bacteria appeared to offer protection, opening the possibility that diet, probiotics or live biotherapeutics could one day support child development. Hein Min Tun, a co-senior author and public health researcher, said the findings suggested a “conversation” between a baby’s biological settings at birth and the gut bacteria acquired during infancy.

The researchers cautioned that autism spectrum disorder and ADHD are complex neurodevelopmental conditions with many genetic and environmental contributors. They stressed that a child’s developmental path is not fixed at birth and that the study identifies only one part of a wider biological picture. The results should therefore not be interpreted as evidence that parents can prevent either condition through probiotics or feeding choices alone.

The work comes as scientific interest grows in the gut-brain axis, the communication network linking intestinal microbes, immune signalling, metabolism and the nervous system. Earlier studies have reported differences in gut microbiota among some children with autism or ADHD, but findings have varied because of differences in diet, medication, gastrointestinal symptoms, study design and sample size. The Hong Kong cohort is significant because it followed children from birth and combined epigenetic, microbiome and behavioural data over time.

The study also has practical limits. Behavioural questionnaires at age three can indicate early traits but do not replace clinical diagnosis. Microbiome patterns can also be affected by geography, diet, antibiotic use, household exposure and health status, meaning results from one cohort may not apply uniformly to other populations.



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