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MATERNAL TRANSFER OF AUTISM-ASSOCIATED MICROBIOTA INDUCES SEX-SPECIFIC HIPPOCAMPAL TRANSCRIPTOMIC ALTERATIONS IN MOUSE OFFSPRING
Arnas Kunevičiusand 5 co-authors
Vilnius University
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS02-07PM-310
Presentation
Date TBA
Board: PS02-07PM-310
Event Information
Poster Board
PS02-07PM-310
Poster
View posterAbstract
Alterations in the gut microbiota have been implicated in autism spectrum disorders (ASD), yet causal mechanisms linking microbiota to neurodevelopmental brain changes remain unclear. We hypothesized that maternal exposure to ASD-associated microbiota during critical developmental windows induces persistent, region-specific transcriptional alterations in the offspring brain.
Fecal microbiota from children with ASD or neurotypical controls was transferred to adult female mice prior to breeding. Adult offspring were assessed for behavior, gut microbiota composition, metabolomic profiles, and spatially resolved brain gene expression using spatial transcriptomics on coronal brain sections.
Maternal transfer of ASD-associated microbiota induced pronounced, sex-specific behavioral abnormalities, including impaired sociability and memory in males and increased anxiety and repetitive behaviors in females. These effects were accompanied by marked alterations in microbial metabolite profiles, despite relatively subtle changes in adult offspring gut microbiota composition, primarily affecting amino acid, lipid, and tryptophan-related pathways. Altered metabolite profiles overlapped with hippocampal transcriptional pathways, supporting a metabolite-mediated link between maternal microbial exposure and brain gene regulation.
Spatial transcriptomic analysis revealed extensive transcriptional reprogramming in the hippocampal pyramidal layer, including downregulation of glutamatergic and cholinergic signaling genes, consistent with disrupted excitatory–inhibitory balance.
Together, these findings identify a metabolite-linked, spatially defined hippocampal transcriptomic signature induced by maternal ASD-associated microbiota, providing mechanistic insight into microbiota-driven neurodevelopmental alterations relevant to ASD.
Fecal microbiota from children with ASD or neurotypical controls was transferred to adult female mice prior to breeding. Adult offspring were assessed for behavior, gut microbiota composition, metabolomic profiles, and spatially resolved brain gene expression using spatial transcriptomics on coronal brain sections.
Maternal transfer of ASD-associated microbiota induced pronounced, sex-specific behavioral abnormalities, including impaired sociability and memory in males and increased anxiety and repetitive behaviors in females. These effects were accompanied by marked alterations in microbial metabolite profiles, despite relatively subtle changes in adult offspring gut microbiota composition, primarily affecting amino acid, lipid, and tryptophan-related pathways. Altered metabolite profiles overlapped with hippocampal transcriptional pathways, supporting a metabolite-mediated link between maternal microbial exposure and brain gene regulation.
Spatial transcriptomic analysis revealed extensive transcriptional reprogramming in the hippocampal pyramidal layer, including downregulation of glutamatergic and cholinergic signaling genes, consistent with disrupted excitatory–inhibitory balance.
Together, these findings identify a metabolite-linked, spatially defined hippocampal transcriptomic signature induced by maternal ASD-associated microbiota, providing mechanistic insight into microbiota-driven neurodevelopmental alterations relevant to ASD.
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