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

作者：Tao Li, Junyu Chen, Kai Mi, Junwen Lei, Zidi Ning, Longya Lu, Zhan Su, Qihui Zhu, Mingyan Lin, Yichao Wang, Juan Wang, Rui Xu, Lora Khaib, Rob Knight, Zhibin Hu, Xingyin Liu · 发表于：Molecular Psychiatry · 年份：2025 · DOI：10.1038/s41380-025-03164-0 · 被引用次数：5 · 研究领域：Neuroendocrine regulation and behavior、Tryptophan and brain disorders、Gut microbiota and health

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 expressi...