(P19-056-25) Functional and Compositional Differences in the Gut Microbiome Between Individuals With and Without a History of Gestational Diabetes

Objectives: Women with gestational diabetes mellitus (GDM) history are at high risk of cardio-metabolic disorders later in their lives, such as type 2 diabetes (T2D) and cardiovascular diseases (CVD). While the gut microbiome has been increasingly recognized as a critical contributor to the development of T2D and CVD, its association with GDM remains unclear. This study examined the compositional and functional differences in the gut microbiome among women with and without GDM history.

Methods: We generated microbiome profiles based on stool samples collected from 704 women in the Nurse Health Study 2 (NHS2) using metagenomic sequencing. PERMANOVA based on the Bray-Curtis dissimilarity metric was applied to quantify the percent of variance in the microbial community explained by GDM status. Principal coordinate analysis (PCoA) was conducted to visualize the association between the GDM history and the overall configuration of the gut microbiome. We further performed stratified analysis and interaction tests to examine whether the associations of GDM history with gut microbial features differ by population and lifestyle factors.

Results: Compared to women with GDM history, the richness index of women without GDM history is significantly higher. GDM history was significantly associated with lower abundance of several microbial species, particularly Blautia coccoides and Clostridium clostridioforme related to the production and regulation of short-chain fatty acids (SCFA). GDM history was significantly associated with higher abundance of superpathway of L-isoleucine biosynthesis I and anhydromuropeptides recycling II. The associations between GDM status and microbial features were more pronounced among women with normal BMI and high alternate Healthy Eating Index (aHEI).

Conclusions: GDM history is associated with specific microbial species and metabolic pathways involved in the production of SCFA, amino acid and peptidoglycan biosynthesis. Further studies are warranted to substantiate this important observation.

Funding Sources: Dean's Office, School of Medicine, National University of Singapore