ArticleNPJ biofilms and microbiomes2026
Parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation patterns and autism-like behaviors in offspring.
Article in NPJ biofilms and microbiomes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition arising from interactions between genetic and environmental factors. The interplay between the microbiota-gut-brain axis and epigenetics has been implicated in ASD, but the extent of their impact remains unclear. We hypothesized that parental gut microbiota dysbiosis shapes cross-generationally shared DNA methylation patterns and ASD-like phenotypes in offspring. Antibiotic-treated adult mice were colonized with fecal microbiota from children with ASD or typically developing (TD) controls, then bred. Colonization with ASD-associated microbiota did not alter parental behavior but induced ASD-like behavioral changes in offspring, accompanied by colonic inflammation and neuronal loss in the hippocampus and striatum. Targeted bisulfite sequencing revealed that ASD-associated microbiota reshaped methylation at ASD-related CpG sites in parental brain, blood, and colon, with a subset of these alterations also observed in offspring tissue. Integrative analyses revealed sex-specific networks linking gut microbes, DNA methylation, gene expression, metabolites, and behavior. These findings support a model in which parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation changes linked to ASD-like phenotypes in offspring. Together, these results provide novel microbial and epigenetic insights into ASD-related risk and offering a plausible mechanistic explanation for the clinical phenomenon in which unaffected parents give rise to children with ASD.
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