Lacticaseibacillus rhamnosus GR-1 prevents autism-like behaviors by reshaping the maternal and offspring microbiome

As a prevalent neurodevelopmental disease, whether ASD (autism spectrum disorder) can be ameliorated by the early use of a single microbe remains unknown. Here we report that Lacticaseibacillus rhamnosus GR-1 (LGR-1) prevented the occurrence of autism-like behaviors when administered exclusively to the pregnant mice, as evidenced by the improved behaviors and restored E/I balance in the prefrontal cortex of male pups. In parallel, the offspring microbiome was reshaped by LGR-1 treatment, mediated by the vertical transmission of maternal microbiome, with its roles validated by microbiota transplant and cross-fostering. In addition to gut commensals, the LGR-1-shaping vaginal microbiota also contributed to the establishment of “beneficial” microbiome. Regarding key taxa in offspring, Akkermansia muciniphila was influenced by LGR-1 and exerted effect on the ensuing behavior, through modulating immune pathways related to IL-17-producing cell population. In conclusion, a single microbe applied in utero protects offspring from autism-like behaviors via microbiome transmission, shedding light on the microbe-based avenue to mitigate the risk of ASD.