Probiotics derived sodium benzoate improves social behavior of offspring exposed in the maternal immune activation through regulation of histone lysine benzoylation in astrocytes.
A probiotic chemical added to mom’s water fixed social memory in autism-model pups by tagging astrocyte genes.
01Research in Context
What this study did
Li and team worked with pregnant mice that got an immune-triggering shot. This maternal immune activation (MIA) makes the pups act like autism models.
The moms then drank water laced with sodium benzoate. This compound comes from a probiotic germ called Lactiplantibacillus plantarum.
When the pups grew up, the researchers watched how they played with stranger mice. They also checked gene tags on brain support cells called astrocytes.
What they found
Pups from benzoate moms spent more time sniffing and following new friends. Their social memory scores jumped back toward normal.
The scientists saw more 'benzoyl' tags on histone proteins inside astrocytes. These tags switch on genes that help cells talk to neurons.
In plain words, a simple food-grade microbe chemical flipped a genetic switch that fixed social behavior in an ASD mouse model.
How this fits with other research
Scior et al. (2023) ran a near-copy test. They used the same MIA mouse setup but fed moms methyl donors like choline. Social play rose, yet the pups also got more anxious. The new benzoate study shows a cleaner win: better social scores without the anxiety bonus.
Mao et al. (2026) looks like the opposite story. In preschoolers with ASD, higher lead-cadmium exposure meant worse social skills. Li’s paper flips the coin: a helpful chemical improved social skills in mice. The clash fades when you see one group studied toxic metals in kids, the other tested a supplement in animals.
Whitehouse et al. (2014) started the maternal-diet trail. Moms who took prenatal vitamins had kids with fewer autistic-like behaviors. Li’s work extends that idea by naming a single microbe chemical and showing how it turns genes on in brain cells.
Why it matters
You can’t pour sodium benzoate into a child’s juice yet. Still, the study gives you fresh language for parent consults: gut microbes make chemicals that can tag genes and shape social growth. Track the family’s diet and supplement history just like you track MOs. Push team-based care with gastro docs or nutritionists when you see feeding issues alongside social delays. Future trials may let you pair probiotic foods with ABA, but for now keep the conversation going.
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02At a glance
03Original abstract
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition increasingly linked to microbiota-gut-brain axis dysregulation, yet the causal microbial mediators and molecular mechanisms remain elusive. Based on our previously published ASD cohort, we discovered that depletion of Lactobacillus species in children with ASD correlates with exacerbated gastrointestinal symptoms and social deficits. Maternal immune activation (MIA) during pregnancy has been established as a critical environmental risk factor for ASD. Furthermore, in the MIA-induced ASD mouse model, we demonstrated that supplementation with Lactiplantibacillus plantarum, or its derived sodium benzoate (NaB), mitigates gut dysbiosis, alleviates deficits of social behavior, glutamate-glutamine levels, and neuronal activity in autistic mice. Single-cell RNA sequencing revealed that NaB restored the genes expression, like Cxcl16, in astrocytes of autistic mice, which is linked to glutamate metabolic activity between neurons and astrocytes. Further, we demonstrated that astrocytes-specific Cxcl16 knock-in hippocampus bypassed microbiota effects to restore social memory in autistic mice. Recent investigations have established NaB as key mediator of histone lysine benzoylation (Kbz), primarily through its role in generating benzoyl-CoA, the essential substrate for this epigenetic modification. Mechanistically, through integrating RNA-seq and Cut & Tag analysis, our findings revealed that NaB boosts Cxcl16 gene expression in astrocytes, possibly by increasing H3K27 benzoylation binding at enhancer regions. This highlights the therapeutic potential of probiotics-derived NaB for ASD and uncovers a novel epigenetic mechanism within the microbiota-gut-brain axis.
Molecular Psychiatry, 2025 · doi:10.1038/s41380-025-03164-0