Association of Gut Microbiota during Early Pregnancy with Risk of Incident Gestational Diabetes Mellitus

Aims: We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Methods: Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. Results: In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. Conclusions: Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.