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 samples from offspring born to mothers with GDM (G-O, n = 29) and non-GDM mothers (C-O, n = 30) was collected and analyzed by 16 S rRNA gene sequencing. Subsequently, two types of infant fecal microbiota were transplanted into pseudo-sterile mouse models maintained on normal diet (ND) and high-fat diet (HFD) for 16 weeks, to investigate the relationship between the fecal microbiota of 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 (p < 0.05). 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 16 S rRNA sequencing results showed that under ND, 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 (all p < 0.05). 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 (p < 0.05). In addition, under HFD, 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 (all p < 0.05). Meanwhile, the fecal acetate content in the FMT from G-O group was significantly higher than that in the FMT from C-O group (p < 0.05).

CONCLUSION

Mothers with GDM are associated with significant gut microbiota dysbiosis in G-O, and transplantation of G-O fecal microbiota is associated with increased fat accumulation and impaired glucose tolerance in mice Therefore, the gut microbiota dysbiosis in G-O is associated with later-life growth abnormalities and increased disease risk, suggesting a potential role in this association.