Pediococcus acidilactici CCFM1344 intervention during pregnancy prevents maternal high-fat diet-induced autism-like behaviors in early-life offspring mice

Maternal health plays a crucial role in fetal neurodevelopment, with high-fat diet (HFD) consumption before or during pregnancy known to induce neurodevelopmental and behavioral abnormalities in offspring. In this study, we assessed whether supplementation with Pediococcus acidilactici CCFM1344 (10⁹ CFU/day, oral gavage) during pregnancy in C57BL/6J mice could serve as an effective strategy to counteract neurodevelopmental impairments in offspring induced by maternal HFD. Female mice (8 weeks old) were used for breeding, and both male and female offspring were included in the analyses. 16S rRNA gene sequencing revealed that CCFM1344 significantly modulated the maternal gut microbiota composition, reduced the Firmicutes-to-Bacteroidetes (F/B) ratio, and enriched beneficial genera Alloprevotella and Rikenellaceae RC9 gut group. Behavioral assessments, including the open field and three-chamber social interaction tests, demonstrated that CCFM1344 effectively ameliorated hyperactivity and social deficits in juvenile offspring, with these behavioral changes showing partial normalization in adulthood. Gut microbiota analysis of the juvenile offspring indicated that CCFM1344 significantly affected microbial diversity and improved ecological stability. In mothers, fecal metabolomics and serum cytokine profiling showed that CCFM1344 intervention regulated key metabolites, including taurine and L-histidine, and modulated inflammatory markers such as TNF-α, IFN-γ, and IL-10. In addition, transcriptomic and quantitative real-time PCR analyses of neonatal brain tissue revealed that CCFM1344 reversed the abnormal expression of genes associated with neuroinflammation and myelination—including Gfap, Mmp9, Il-1β, and Mobp—with these changes normalizing by adulthood. In conclusion, pregnancy-specific administration of CCFM1344 modulated the maternal gut microbiota and immunometabolic environment, alleviating HFD-induced impairments in early brain development and behavior in offspring. These findings highlight the critical importance of probiotic interventions during pregnancy in supporting neurodevelopmental health in the next generation.