Maternal gestational diabetes mellitus leads to adverse growth patterns and disease risk in offspring in vivo: evidence from cross-generational effects on gut microbiota

Background: Gestational diabetes mellitus (GDM) is an important risk factor for metabolic diseases such as obesity in its offspring, and this effect may be mediated by altering the infant's gut microbiota.Methods: Fecal from offspring born to mothers with GDM (G-O) and non-GDM mothers (C-O) was collected and analyzed by 16S rRNA gene sequencing. Subsequently, two types of fecal microbiota were transplanted into pseudo-sterile mouse models with normal diet (ND) and high-fat diet (HFD), respectively, to investigate the relationship between fecal microbiota of the offspring of GDM and the risk of diseases such as obesity and dysglycemia in their later life.Results: Significant differences in gut microbial composition between G-O and C-O. Fecal microbiota transplantation (FMT) from G-O resulted in obesity, hypertrophy of adipocytes in white adipose tissue (WAT), and abnormal glucose tolerance compared to mice that received FMT from C-O. The 16S rRNA sequencing results showed that under ND conditions, the abundance of the potentially pathogenic bacteria Eubacterium_nodatum_group and Lachnoclostridium was significantly increased in the FMT from G-O group, while the abundance of the beneficial bacteria Acetatifactor, Muribaculum, and Lactobacillus was significantly decreased. Further analysis showed that fecal isobutyrate levels were significantly lower in the FMT from G-O group compared to the FMT from C-O group. In addition, under HFD conditions, the FMT from G-O group enriched the abundance of Alistipes, Rikenellaceae_RC9_gut_group, Rikenella, and Bilophila, while the abundance of Akkermansia, Faecalibaculum, and Lactobacillus showed a decrease. Meanwhile, the fecal acetate content in the FMT from G-O group was significantly higher than that in the FMT from C-O group.Conclusion: The dysbiosis of the gut microbiota in G-O contributes to their later adverse growth patterns and increased disease risk.