The purpose of this study was to explore the relationship between the characteristics of gut microbiome and the effect of medical nutrition therapy (MNT) on glycemic control in pregnant women with gestational diabetes mellitus (GDM). Seventy-four pregnant women newly diagnosed with GDM received MNT for one-week. The effect of glycemic control was evaluated by fasting and 2-hour postprandial blood glucose; and stool samples of pregnant women were collected to detect the gut microbiome before and after MNT. We used a nested case-control study design, with pregnant women with GDM who did not meet glycemic standards after MNT as the ineffective group and those with an age difference of ≤5 years, matched for pre-pregnancy body mass index (BMI) 1:1, and meeting glycemic control criteria as the effective group. Comparison of the gut microbiome characteristics before MNT showed that the ineffective group was enriched in Desulfovibrio, Aeromonadales, Leuconostocaceae, Weissella, Prevotella, Bacillales_Incertae Sedis XI, Gemella and Bacillales, while the effective group was enriched in Roseburia, Clostridium, Bifidobacterium, Bifidobacteriales, Bifidobacteriaceae, Holdemania and Proteus. After treatment, the effective group was enriched in Bifidobacterium and Actinomycete, while the ineffective group was enriched in Holdemania, Proteus, Carnobacteriaceae and Granulicatella. In conclusion, the decrease in the abundance of characteristic gut microbiome positively correlated with blood glucose may be a factor influencing the poor hypoglycemic effect of MNT in pregnant women with GDM. Abundance of more characteristic gut microbiome negatively correlated with blood glucose could help control blood glucose in pregnant women with GDM.

Periconceptional folate supplementation is prevalent, raising concerns about possible side effects. The aim of this study was to investigate the associations of folic acid supplementation, dietary folate, serum folate with gestational diabetes mellitus (GDM) risk. In this matched case-control study, 81 pregnant women with GDM (cases) and 81 pregnant women with non-GDM (controls) were identifi ed through age difference (Յ3 y) and parity (Both primipara or multipara women) matching, and serum folate levels were measured during the GDM screening (24-28 gestational wk). Folic acid supplementation and dietary folate intake from three months prepregnancy through midpregnancy were assessed using a self-reported questionnaire and food frequency questionnaire. Multivariate binary logistic regression models were used to evaluate the association between folate and GDM. After adjusting for confounding factors, we observed that compared with folic acid supplementation dose Յ400 g/d, pregnancies without folic acid supplementation and supplemental dose Ͼ800 g/d were associated with GDM risk (adjusted odds ratioϭ7.25, 95% confidence interval: 1.34-39.36; adjusted odds ratioϭ4.20, 95% confi dence interval: 1.03-17.22), while no signifi cant association with a 400-800 g/d dose of folic acid supplementation and GDM. Compared with folic acid supplementation dose Յ24 wk, pregnancies without folic acid supplementation were associated with GDM risk (adjusted odds ratioϭ6.70, 95% confi dence interval: 1.22-36.77), while no signifi cant association with folic acid supplementation dose Ͼ24 wk and GDM. No signifi cant association of dietary folate and serum folate with GDM was found. No or a higher dose of folic acid supplementation would increase GDM risk and a dose of Ͻ800 g/d is the safe dose.

Although previous studies have reported that serum folate levels are negatively associated with depression in women but not men, it remains unclear whether folate deficiency can directly lead to depression and whether sex difference serves a role in this condition, since the potential mechanism remains elusive. Therefore, the present study aimed to investigate whether folate deficiency results in differences in parameters associated with depression between males and females. CD-1 mice received either a standard control diet or a folate-deficient diet from 10 to 38 weeks of age, following which behavioral assays, such as an open field test, sucrose preference test and forced swim test were performed throughout week 38. Serum and cerebral cortex samples were subsequently collected for assessment. Serum folate, homocysteine, estradiol (E2) and testosterone levels were measured using chemiluminescence, enzymatic cycling assay and electrochemiluminescence immunoassays. The cerebral cortex was used for western blot analysis, to detect the expression levels of estrogen receptor β (ERβ), PI3K/AKT pathway and caspase-3. The results revealed that compared with those in female mice that received standard control diet, female mice that received folate-deficient diet exhibited lower E2 concentrations, lower sucrose preferences (as determined through the sucrose preference test), longer durations of immobility (as determined in the forced swim test) and less time spent in the central areas of the open field test. Western blotting demonstrated that the expression levels of ERβ and the phosphorylation levels of PI3K and AKT were decreased, whilst the expression levels of cleaved caspase-3 were increased, in the cerebral cortex of female mice that received folate-deficient diet. However, no differences in E2 concentration, behavioral assay parameters or protein levels of ERβ, phosphorylated (p-)PI3K, p-AKT and cleaved caspase-3 could be observed in male mice regardless of whether they received standard control or folate-deficient diets. Collectively, these results revealed that folate deficiency only led to depression-like behavior in female mice. This may be associated with reduced E2 levels, which may inhibit the PI3K/AKT pathway and upregulate the expression of cleaved caspase-3 to promote neuronal apoptosis.

The DOHaD theory suggests that adverse environmental factors in early life may lead to the development of metabolic diseases including diabetes and hypertension in adult offspring through epigenetic mechanisms such as DNA methylation. Folic acid (FA) is an important methyl donor in vivo and participates in DNA replication and methylation. The preliminary experimental results of our group demonstrated that lipopolysaccharide (LPS, 50 µg/kg/d) exposure during pregnancy could lead to glucose metabolism disorders in male offspring, but not female offspring; however, the effect of folic acid supplementation on glucose metabolism disorders in male offspring induced by LPS exposure remains unclear. Therefore, in this study, pregnant mice were exposed to LPS on gestational day (GD) 15–17 and were given three doses of FA supplementation (2 mg/kg, 5 mg/kg, or 40 mg/kg) from mating to lactation to explore its effect on glucose metabolism in male offspring and the potential mechanism. This study confirmed that FA supplementation of 5 mg/kg in pregnant mice improved glucose metabolism in LPS-exposed offspring during pregnancy by regulating gene expression.

Maternal lipopolysaccharide (LPS) exposure during pregnancy induces metabolic abnormalities in male offspring, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of maternal LPS exposure during pregnancy on metabolic profiling of maternal serum and male fetal liver using Liquid Chromatograph Mass Spectrometer techniques. From day 15 to day 17 of gestation, pregnant mice were administered intraperitoneal LPS (experimental group) (50 μg/kg/d) or saline (control group). On day 18 of gestation, maternal serum and male fetal liver were collected. After LPS exposure, levels of 38 and 75 metabolites, mainly glycerophospholipid and fatty acid metabolites, were altered in maternal serum and male fetal liver, respectively. It was found that in maternal serum and male fetal livers, the glycerophospholipids containing saturated fatty acids (SFAs) and the SFAs were upregulated, while the glycerophospholipids containing polyunsaturated fatty acids (PUFAs) and the PUFAs were downregulated. This concordance between maternal and fetal alterations in glycerophospholipid and fatty acid metabolites may be a metabolomic signature of the early intrauterine period and may provide insight into the mechanisms by which maternal LPS exposure induces disorders of glucose metabolism in male offspring.