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Changes in gut microbiota and metabolites of mice with intravenous graphene oxide-induced embryo toxicity

  • Xiaojing Liu (Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University) ;
  • Zengjin Wang (Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University) ;
  • Chuanfeng Teng (School of Chemistry and Chemical Engineering, Shandong University) ;
  • Zhiping Wang (Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University)
  • 투고 : 2023.12.22
  • 심사 : 2024.04.24
  • 발행 : 2024.10.15

초록

The expanding applications of graphene oxide (GO) nanomaterials have attracted interest in understanding their potential adverse effects on embryonic and fetal development. Numerous studies have revealed the importance of the maternal gut microbiota in pregnancy. In this study, we established a mouse GO exposure model to evaluate embryo toxicity induced by intravenous administration of GO during pregnancy. We also explored the roles of gut microbiota and fecal metabolites using a fecal microbiota transplantation (FMT) intervention model. We found that administration of GO at doses up to 1.25 mg/kg caused embryo toxicity, characterized by significantly increased incidences of fetal resorption, stillbirths, and decreased birth weight. In pregnant mice with embryo toxicity, the richness of the maternal gut microbiota was dramatically decreased, and components of the microbial community were disturbed. FMT alleviated the decrease in birth weight by remodeling the gut microbiota, especially via upregulation of the Firmicutes/Bacteroidetes ratio. We subsequently used untargeted metabolomics to identify characteristic fecal metabolites associated with GO exposure. These metabolites were closely correlated with the phyla Actinobacteria, Proteobacteria, and Cyanobacteria. Our findings offer new insights into the embryo toxic effects of GO exposure during pregnancy; they emphasize the roles of gut microbiota-metabolite interactions in adverse pregnancy outcomes induced by GO or other external exposures, as demonstrated through FMT intervention.

키워드

과제정보

This work was supported by Beijing Natural Science Foundation (No. 7234401) and China Postdoctoral Science Foundation (No. 88014Y0226), and National Natural Science Foundation of China (No. 81472950).

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