AimsGestation is linked to changes in gut microbiota composition and function. Since gestational diabetes mellitus (GDM) can develop at any time of the pregnancy, we stratified the women into four groups according to the time and test used for the diagnosis. We focused on the gut microbiota pattern in early pregnancy to detect changes which could be linked to later GDM development.MethodsWe collected stool samples from 104 pregnant women including obese individuals (first trimester body mass index median was 26.73). We divided the women into four groups according to routine screening of fasting plasma glucose (FPG) levels and oral glucose tolerance test (oGTT) in the first and third trimesters, respectively. We processed the stool samples for bacterial 16S rRNA and fungal ITS1 genes sequencing by Illumina MiSeq approach and correlated the gut microbiota composition with plasma short-chain fatty acid levels (SCFA).ResultsWe found that gut bacterial microbiota in the first trimester significantly differs among groups with different GDM onset based on unweighted UniFrac distances (p=0.003). Normoglycemic women had gut microbiota associated with higher abundance of family Prevotellaceae, and order Fusobacteriales, and genus Sutterella. Women diagnosed later during pregnancy either by FGP levels or by oGTT had higher abundances of genera Enterococcus, or Erysipelotrichaceae UCG-003, respectively. We observed significant enrichment of fungal genus Mucor in healthy pregnant women whereas Candida was more abundant in the group of pregnant women with impaired oGTT. Using correlation analysis, we found that Holdemanella negatively correlated with Blautia and Candida abundances and that Escherichia/Shigella abundance positively correlated and Subdoligranulum negatively correlated with plasma lipid levels. Coprococcus, Akkermansia, Methanobrevibacter, Phascolarctobacterium and Alistipes positively correlated with acetate, valerate, 2-hydroxybutyrate and 2-methylbutyrate levels, respectively, in women with GDM.ConclusionsWe conclude that there are significant differences in the gut microbiota composition between pregnant women with and without GDM already at the early stage of pregnancy in our cohort that included also overweight and obese individuals. Specific microbial pattern associated with GDM development during early pregnancy and its correlation to plasma lipid or SCFA levels could help to identify women in higher risk of GDM development.
Gestational diabetes mellitus (GDM) represents a heterogeneous group of hyperglycemic metabolic disorders that are associated with health outcomes for mothers and offspring. Currently, diagnosis of GDM is based on repetitive measurement of increased fasting plasma glucose (FPG) or upon results showing increased postprandial plasma glucose (PPG). Recently, it was discovered that the changes in the gut microbiome during pregnancy are associated with insulin resistance and obesity. Therefore, in this study, relevant products of gut bacteria, short-chain fatty acids (SCFA) and their derivatives were evaluated together with baseline body composition characteristics and common biochemical parameters in women with three different phenotypes of GDM, healthy pregnant and nonpregnant women. Plasma SCFA and their derivatives were derivatized, separated on reversed-phase liquid chromatography and detected by a triple-quadrupole mass spectrometer. 3-hydroxybutyrate (3-OH-BA), 4-methylvalerate (4-MVA) and isovalerate (IVA), together with selected parameters associated with baseline body composition characteristics and biochemistry, were evaluated as statistically significant. 3-OH-BA, which was increased in all three groups of women with different phenotypes of GDM, reflects a ketogenic state of GDM. In all groups of pregnant women, elevated/suppressed concentrations of 4-MVA/IVA were found. These findings show the importance of monitoring SCFA and other parameters besides glucose in women with GDM.
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