Integrated microbiome–metabolome analysis reveals novel associations between fecal microbiota and hyperglycemia-related changes of plasma metabolome in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) has been associated with circulating metabolic disorders and alterations in gut microbiota, respectively. Although changes in gut microbiota contribute to metabolic diseases, the connections between gut microbiota and the circulating metabolic state in GDM remain largely undetermined. To investigate the associations between gut microbiota and the circulating metabolome of GDM, we enrolled 40 pregnant women (20 with GDM and 20 non-diabetic control), and performed multi-omics association (MOA) study on 16s rRNA sequencing of fecal microbiota and (1)H-NMR profiling of the plasma metabolome. The results suggested that both fecal microbiota and the plasma metabolome of the enrolled pregnant women could be separated along the vector of hyperglycemia. A close correlation between fecal microbiota and the plasma metabolome of GDM was observed by MOA approaches. Redundancy Analysis identified five plasma metabolites (glycerol, lactic acid, proline, galactitol and methylmalonic acid) and 98 members of fecal microbiota contributing to the close correlation between the plasma metabolome and fecal microbiota. Further spearman rank correlation analysis revealed that four out of five of the identified plasma metabolites (except galactitol) were correlated with hyperglycemia. Co-occurring network analysis suggested that 15 out of 98 of the members of fecal microbiota were positively correlated with each other, forming a co-occurring cohort (mainly consisted of the phylum Firmicutes). The results of this study demonstrated that alterations in fecal microbiota were associated with hyperglycemia related changes of the plasma metabolome of women with GDM, suggesting novel therapies against gut microbiota to alleviate GDM.