EARLY microbiome maturation may modify the impact of perinatal epigenetic changes associated with neurodevelopmental disorders, according to findings from a large longitudinal birth cohort study.
Microbiome Maturation and Early Life Programming
Epigenetic regulation and microbiome maturation are known to be sensitive to perinatal influences. Researchers investigated how early life disruptions to the host epigenome and microbial colonisation interact with neuroimmune pathways that may contribute to later neurodevelopmental outcomes.
The study analysed 571 cord blood methylomes and 5328 gut metagenomes collected from infants and their parents across 969 families. The aim was to characterise interactions between the microbiome and epigenome during early development and to determine their potential relationship with neurodevelopmental disorders.
Investigators found that caesarean section delivery was associated with differential methylation of genes involved in immune responses and neural development. In parallel, caesarean section delivery reduced vertical transmission of the maternal microbiome. This reduction appeared to be partially compensated by transmission from the paternal microbiome.
Epigenetic Changes Linked to Neurodevelopment
Further analyses identified associations between cord blood methylation patterns and neurodevelopmental outcomes assessed at age 3 years. Children with hypermethylated genes involved in neurogenic and neurotransmission pathways demonstrated higher scores for autism spectrum disorder and attention deficit hyperactivity disorder.
These findings suggest that epigenetic alterations present at birth may be linked to developmental pathways associated with neurodevelopmental disorders. The results also support a potential role for perinatal exposures in shaping both microbial colonisation and epigenetic regulation during a critical developmental window.
Microbiome Maturation May Mitigate Risk
Importantly, the study identified evidence that specific microbial species may modify associations between epigenetic alterations and neurodevelopmental outcomes. The presence of Lachnospira pectinoschiza at 12 months appeared to mitigate the potential adverse effect of hypermethylation of SLC5A3, a gene implicated in neurodevelopmental processes, on autism spectrum disorder risk (p<0.001). The bacterium also mediated 7.97% of this association.
Similarly, colonisation by Parabacteroides distasonis at 2 months partly alleviated associations between attention deficit hyperactivity disorder scores and methylation levels of several genes involved in neural function, neurotransmission, and transport across the blood brain barrier, including SLC7A1, GABBR1, KCNA1, LRP2, PSMG1, and VIP. The authors also reported that 8.0%–16.76% of these associations were mediated by the absence of P. distasonis colonisation.
The findings suggest that early microbial colonisation may influence the relationship between epigenetic regulation and neurodevelopment, highlighting microbiome dependent mechanisms that could contribute to the developmental origins of neurodevelopmental disorders.
Reference
Ng S et al. Epigenome-microbiome interplay in early life associates with infants’ neurodevelopmental outcomes. Cell Press Blue. 2026;1.
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