Dysbiosis of gut microbiota has been linked to gestational diabetes mellitus (GDM), and grows as a resource for GDM biomarkers. However, the contributions of gut microbiota to GDM remain incompletely understood. Metabolites are key messengers in the interactions between gut microbiota and the host. Metabolomics is emerging as an essential tool in exploring the contributions of gut microbiota to diseases. In this study, we performed 1H-NMR based metabolomics on the feces of 62 pregnant women, including 31 women with GDM, and 31 women as the non-diabetes (NDM) control. Using Principle Component Analysis (PCA) and Orthogonal Projection to Latent Structures Discrimination Analysis (OPLS-DA), we observed clear cluster separation of the fecal metabolome between women with GDM and the NDM control. We further applied several feature selection methods to find five fecal metabolites contributing to the cluster separation of the fecal metabolome. These five metabolites, namely dibutyl decanedioate, N-acetylgalactosamine-4-sulphate, homocysteine, l-malic acid, and butanone, were significantly correlated with the clinical indices of GDM. Metabolite enrichment and pathway analysis on the five metabolites suggested that the fecal citrate cycle and sulfur metabolism were correlated with GDM. The results of this study demonstrated that disorders in the fecal metabolome are associated with GDM.
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