Parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation patterns and autism-like behaviors in offspring

Jun 11, 2026NPJ biofilms and microbiomes

Unhealthy gut bacteria in parents are linked to shared DNA changes and autism-like behaviors in their children

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Abstract

Colonization with ASD-associated microbiota induced ASD-like behavioral changes in offspring in a mouse study.

Parental gut microbiota dysbiosis may influence DNA methylation patterns across generations.
Offspring exhibited ASD-like behaviors alongside colonic inflammation and neuronal loss.
ASD-associated microbiota altered methylation at specific sites in parental and offspring tissues.
Integrative analyses suggested sex-specific connections between gut microbes and behavior.

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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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Gut-Brain AxisIssue #41

Gut bacteria from kids with autism caused autism-like behaviors when transplanted into mice

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Parental gut microbiota dysbiosis is associated with cross-generationally shared DNA methylation patterns and autism-like behaviors in offspring

Abstract

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