Gut microbiota remodeling exacerbates neuroinflammation and cognitive dysfunction via the microbiota-gut-brain axis in prenatal VPA-exposed C57BL/6 mice offspring.

Scientists studied how a medication called valproic acid affects unborn mice and their development. Mice exposed before birth showed autism-like behaviors such as social problems and repetitive actions. They also had unhealthy gut bacteria and brain inflammation. This research suggests that gut health and brain function are connected, and that treatments targeting gut bacteria might help with autism symptoms.

This animal study examined how prenatal valproic acid (VPA) exposure affects gut bacteria, brain inflammation, and behavior in mice. Researchers found that VPA-exposed mice showed autism-like behaviors including social difficulties, repetitive behaviors, and memory problems. These mice also had significant changes in their gut bacteria composition, with reduced beneficial bacteria that produce short-chain fatty acids. The study demonstrated increased brain inflammation, overactive immune cells in the brain, and disrupted antioxidant systems.

The findings suggest that gut bacteria changes may contribute to autism-like symptoms through the gut-brain connection, supporting the potential for gut-targeted treatments in neurodevelopmental disorders.

Results support the gut-brain axis as a potential therapeutic target for autism. The identification of specific bacterial changes and inflammatory pathways may inform development of microbiota-based interventions. However, translation to human populations requires careful validation given the animal model limitations.

This is an animal study using mice, so findings may not directly translate to humans. Sample size is not reported, making it difficult to assess statistical power. The study design type is unclear, and causal relationships between gut bacteria changes and behavioral outcomes need further validation.

Prenatal exposure to valproic acid (VPA) is a recognized risk factor for autism spectrum disorder (ASD)-like phenotypes, yet the mechanisms linking gut microbiota dysbiosis to neurodevelopmental impairments remain poorly understood. Emerging evidence implicates the microbiota-gut-brain axis as a critical mediator of neuroinflammation and cognitive deficits, but causal pathways in VPA-induced ASD models require systematic exploration. This study investigates how prenatal VPA exposure reshapes gut microbiota composition, exacerbates neuroinflammatory responses, and drives cognitive dysfunction through the microbiota-gut-brain axis in C57BL/6 mouse offspring. Prenatal VPA-exposed and control offspring underwent behavioral assessments (open field, three-chamber social interaction, marble-burying, and Morris water maze tests).

Neuroinflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10), oxidative stress markers (GSH, SOD, MDA), and microglial activation (Iba1 immunofluorescence) were quantified. Gut microbiota profiles were analyzed via 16S rRNA sequencing, with functional pathway predictions using PICRUSt2 and KEGG databases. VPA-exposed mice exhibited ASD-like behaviors, including social deficits, repetitive stereotypic actions, and impaired spatial memory. Neuroinflammation was marked by upregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and microglial hyperactivation, alongside suppressed antioxidant systems (GSH, SOD).

Gut microbiota analysis revealed dysbiosis characterized by reduced Bacteroidia and enriched Clostridia, with diminished short-chain fatty acid (SCFA)-producing taxa (e.g., Oscillibacter). Co-occurrence networks highlighted disrupted microbial interactions, while functional profiling indicated impaired carbohydrate metabolism and elevated neurotoxic pathway activity. Prenatal VPA exposure induces gut microbiota remodeling that exacerbates neuroinflammation and cognitive dysfunction via the microbiota-gut-brain axis. This study provides evidence for linkages between taxonomic and metabolic gut dysbiosis and ASD-like pathophysiology, underscoring the therapeutic potential of microbiota-targeted interventions for neurodevelopmental disorders.