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<p>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 used a lactobacillus strain, <i>Lacticaseibacillus rhamnosus</i> GR-1 (LGR-1), for prenatal intervention in autism-like mice with either environmental or idiopathic origins by exclusively administering to the pregnant dams at a dose of 10<sup>9</sup>/mouse/day, followed by offspring behavioral assessment with 3-chamber trial and marble burying test. The results revealed that LGR-1 prevented the occurrence of autism-like symptoms, as evidenced by the improved behaviors and restored E/I (excitatory-inhibitory) balance in the prefrontal cortex of male pups. In parallel, the offspring microbiome was reshaped by LGR-1 treatment, probably mediated by the vertical transmission of maternal microbiome, with its roles further unraveled by fecal microbiota transplant and cross-fostering experiments. In addition to gut commensals, the LGR-1-shaping vaginal microbiota also contributed to the establishment of “beneficial” microbiome. Regarding key taxa in offspring, <i>Akkermansia muciniphila</i> was influenced by LGR-1 and exerted impact on behaviors via pathways related to IL-17-producing lymphocytes. Our findings demonstrate that prenatal microbial administration protects offspring against autism-like behavioral phenotypes through microbiome transmission, highlighting a potential microbe-based therapeutic avenue to mitigate ASD risk.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月24日

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  • Ruili Yang,
  • Yi Xu,
  • Jinchun Xu,
  • Chengqing Huang,
  • Feng Zhu,
  • Tian Wang,
  • Rui Kong,
  • Jie Xiao,
  • Biao He,
  • Xiaozhen Gu,
  • Hui-Li Wang

摘要

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 used a lactobacillus strain, Lacticaseibacillus rhamnosus GR-1 (LGR-1), for prenatal intervention in autism-like mice with either environmental or idiopathic origins by exclusively administering to the pregnant dams at a dose of 109/mouse/day, followed by offspring behavioral assessment with 3-chamber trial and marble burying test. The results revealed that LGR-1 prevented the occurrence of autism-like symptoms, as evidenced by the improved behaviors and restored E/I (excitatory-inhibitory) balance in the prefrontal cortex of male pups. In parallel, the offspring microbiome was reshaped by LGR-1 treatment, probably mediated by the vertical transmission of maternal microbiome, with its roles further unraveled by fecal microbiota transplant and cross-fostering experiments. 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 impact on behaviors via pathways related to IL-17-producing lymphocytes. Our findings demonstrate that prenatal microbial administration protects offspring against autism-like behavioral phenotypes through microbiome transmission, highlighting a potential microbe-based therapeutic avenue to mitigate ASD risk.