Alterations in the gut microbiota and the faecal metabolomes are potentially associated with gestational diabetes mellitus through inflammatory response

Gestational diabetes mellitus (GDM) is a disease of glucose intolerance that first occurs during pregnancy. Accumulating evidence underlined a link between gut microbiota dysbiosis and GDM, and microbial metabolites represent a unique way to explore microbiota-host interactions. However, the associations between changes in the gut microbiota and microbial metabolites and immune homeostasis in the GDM pathogenesis remain largely unclear. In this prospective study, the characteristics of gut microbiota in both first trimester (T1) and second trimester (T2) were investigated in 46 GDM patients and 44 matched controls. We comprehensively profiled the microbial metabolites using non-targeted metabolomics and quantitatively targeted metabolomics, measurements of inflammatory cytokines and biomarkers of intestinal barrier function, and combined with correlation analysis in T2. Gut microbiota dybiosis was observed in GDM patients in both T1 and T2, and was characterised by the enrichment of multiple potentially harmful bacteria, such as UBA1819 and Erysipelatoclostridium. Besides, alterations in the microbiota were accompanied by a disturbance in tryptophan metabolism, mainly manifested as a shift towards the production of more kynurenine and less indole derivatives. Most importantly, correlation network analysis indicated that overgrowth of potential pathogens and tryptophan metabolism disorder were associated with inflammatory imbalance and disrupted epithelial barrier in GDM patients. These findings provide a greater understanding of the pathogenesis and new targets for microecological interventions by mediating tryptophan metabolism in GDM.