Introduction & Objective: Maternal hyperglycemia during pregnancy (HIP) poses health risks to mothers and offspring, with unclear mechanisms. Our previous studies have confirmed that dysregulated vertical transmission of microbiota is one of the causes of abnormal glucose metabolism in offspring. This study further explored the effect of microbiota transmission on progeny glucose metabolism and elucidate the mechanism.
Methods: The feces of HIP mother mice in the previous study were colonized into germ-free mice, and after the difference in glucose metabolism, they were impregnated to produce offspring. OGTT were used to evaluate progeny glucose metabolism, 16S rRNA sequencing was used to detect fecal microbiota, and bile acid profiles of fecal metabolites were detected by targeting bile acid metabolites. To screen possible pathways using transcriptomic sequencing of the mouse liver for further validation at the protein and gene levels.
Results: The colonization of germ-free maternal mice with HIP’s microbiota adversely affected glucose metabolism, liver development, and RNA methylation levels in offspring. The vertical transmission of key bacteria such as Bifidobacterium choerinum is consistent with the intergenerational inheritance of abnormal glucose metabolism. Also, a significant descending of bile acid HDCA in maternal and offspring mice was observed, leading to an impaired bile acid gut-liver axis and aberrent gene expression in bile acid metabolism. Validation experiments showed the impact of varying HDCA levels on RNA methylation levels and key metabolic factors in liver cells. HDCA concentration was significantly positively correlated with the expression of SOCS3, INSR, etc. in hepatocytes.
Conclusion: Abnormal microbiota transmission caused dysregulated microbiota and reduced HDCA in HIP’s offspring, while HDCA induced elevated RNA methylation, improving metabolic gene expression.
Q. Xie: None. H. Yuan: None.
