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.