NPJ biofilms and microbiomesJun 11, 2026

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

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

In a mouse microbiota-transfer model, parental gut dysbiosis linked to autism was associated with shared DNA methylation changes across generations and autism-like behaviors in offspring.

Evidence

This preclinical study colonized antibiotic-treated adult mice with fecal microbiota from children with autism spectrum disorder or typically developing controls before breeding, then used behavioral assays, tissue pathology, targeted bisulfite sequencing, and integrative multi-omic analyses to find offspring ASD-like behaviors, colonic inflammation, neuronal loss, and overlapping parental-offspring methylation changes at ASD-related CpG sites.

Caveat

The evidence comes from a mouse fecal-microbiota-transfer model and shows association with cross-generational methylation patterns, not direct proof that these microbial or epigenetic changes cause autism in humans.

Simplified

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.