Gut microbiome interacts with pregnancy hormone metabolites in gestational diabetes mellitus

Abstract

IntroductionChange in the composition of intestinal microbiota is associated with metabolic disorders such as gestational diabetes mellitus (GDM).MethodsTo understand how the microbiota impacts the development of gestational diabetes mellitus, we profiled the intestinal microbiome of 54 pregnant women, including 27 GDM subjects, by employing 16S rRNA gene sequencing. Additionally, we conducted targeted metabolomics assays to validate the identified pathways with overrepresented metabolites.ResultsWe evaluated the patterns of changing abundances of operational taxonomic units (OTU) between GDM and the healthy counterparts over three timepoints. Based on the significant OTUs, we inferred 132 significantly altered metabolic pathways in GDM. And identified two overrepresented metabolites of pregnancy hormone, butyrate and mevalonate, as potential intermediary metabolites of intestinal microbiota in GDM. Finally, we validated the impacts of the intestinal microbiota on GDM by demonstrating consistent changes of the serum levels of progesterone, estradiol, butyrate, and mevalonate in an independent cohort.DiscussionOur findings confirm that alterations in the microbiota play a role in the development of GDM by impacting the metabolism of pregnancy hormones. This provides a novel perspective on the pathogenesis of GDM and introduces potential biomarkers that can be used for early diagnosis and prevention of the disease.

Maternal gut microbiota in the health of mothers and offspring: from the perspective of immunology

“…Although growing evidence showed a correlation between the altered gut microbiota and GDM, few studies have investigated the mechanisms underlying the dysbiosis of the gut microbiota that leads to the development of GDM ( Figure 1 ). Recent studies found that the insufficiency of circulating dopamine, imbalanced production of SCFAs, and excessive inflammation resulting from the dysbiosis of the gut microbiota led to the development of GDM ( 133 , 135 , 136 ). Meanwhile, restoring the balance of maternal gut microbiota limited the inflammatory response by increasing the production of Tregs, Tfrs, Bregs in the GDM mice model ( 47 ).…”