Probiotics derived sodium benzoate improves social behavior of offspring exposed in the maternal immune activation through regulation of histone lysine benzoylation in astrocytes.

Researchers studied how gut bacteria might affect autism symptoms. They found that children with autism often have lower levels of certain helpful bacteria called Lactobacillus. In mouse studies, giving a compound called sodium benzoate (made by these bacteria) improved social behaviors in mice with autism-like symptoms. The treatment seemed to work by changing how genes are turned on and off in brain cells, particularly affecting communication between brain cells.

This suggests that treatments targeting gut bacteria might help with autism symptoms.

This study investigated the role of Lactobacillus depletion in autism spectrum disorder and tested sodium benzoate (NaB) derived from Lactiplantibacillus plantarum as a potential intervention. Using a maternal immune activation mouse model of ASD, researchers found that NaB supplementation improved social behavior deficits and restored gut microbiome balance. The mechanism appears to involve epigenetic modifications through histone lysine benzoylation, specifically targeting astrocytes in the brain. Single-cell RNA sequencing revealed NaB restored Cxcl16 gene expression in astrocytes, which is linked to glutamate metabolism between neurons and astrocytes.

The study suggests NaB works by increasing H3K27 benzoylation at enhancer regions, highlighting a novel epigenetic pathway in the microbiota-gut-brain axis.

Results suggest probiotic supplementation, particularly Lactobacillus species, may benefit individuals with ASD who have gut dysbiosis. However, human clinical trials are needed before recommending sodium benzoate supplementation. Findings support assessing gut microbiome status in ASD evaluation and considering microbiota-targeted interventions as part of comprehensive treatment approaches.

Study type and sample sizes not reported in abstract. Findings primarily based on mouse model with limited human data mentioned. Mechanistic findings require replication. Long-term safety and efficacy of sodium benzoate supplementation in humans with ASD not established.

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.