Background: Dysbiosis of human gut microbiota is associated with a wide range of metabolic disorders, including gestational diabetes mellitus (GDM). Yet whether gut microbiota dysbiosis participates in the etiology of GDM remains largely unknown. Objectives: Our study was initiated to determine whether the alternations in gut microbial composition during early pregnancy linked to the later development of GDM, and explore the feasibility of microbial biomarkers for the early prediction of GDM. Study design: This nested case-control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Gut microbiota profiles of 98 subjects with GDM and 98 matched healthy controls during the early pregnancy (10-15 weeks) were assessed via 16S rRNA gene amplicon sequencing of V4 region. The data set was randomly split into a discovery set and a validation set, the former was used to analyze the differences between GDM cases and controls in gut microbial composition and functional annotation, and to establish an early identification model of GDM, then the performance of the model was verified by the external validation set. Results: Bioinformatic analyses revealed changes to gut microbial composition with significant differences in relative abundance between the groups. Specifically, Eisenbergiella, Tyzzerella 4, and Lachnospiraceae NK4A136 were enriched in the GDM group, whereas Parabacteroides, Megasphaera, Eubacterium eligens group, etc. remained dominant in the controls. Correlation analysis revealed that GDM-enriched genera Eisenbergiella and Tyzzerella 4 were positively correlated with fasting blood glucose levels, while three control-enriched genera (Parabacteroides, Parasutterella, and Ruminococcaceae UCG 002) were the opposite. Further, GDM functional annotation modules revealed enrichment of modules for sphingolipid metabolism, starch and sucrose metabolism, etc., while lysine biosynthesis and nitrogen metabolism were reduced. Finally, five genera and two clinical indices were included in the linear discriminant analysis model for the prediction of GDM; the areas under receiver operating characteristic curves of the training and validation sets were 0.736 (95% confidence interval: 0.663-0.808) and 0.696 (0.575-0.818), respectively. Conclusions: Gut bacterial dysbiosis in early pregnancy was found to be associated with the later development of GDM, and gut microbiota-targeted biomarkers might be utilized as potential predictors of GDM.

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