Effects of folic acid supplementation in pregnant mice on glucose metabolism disorders in male offspring induced by lipopolysaccharide exposure during pregnancy.

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.

Association of Folic Acid Supplementation, Dietary Folate Intake and Serum Folate Levels with Risk of Gestational Diabetes Mellitus: A Matched Case-Control Study.

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 identified through age difference (≤3 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 ≤400 µg/d, pregnancies without folic acid supplementation and supplemental dose >800 µg/d were associated with GDM risk (adjusted odds ratio=7.25, 95% confidence interval: 1.34-39.36; adjusted odds ratio=4.20, 95% confidence interval: 1.03-17.22), while no significant association with a 400-800 µg/d dose of folic acid supplementation and GDM. Compared with folic acid supplementation dose ≤24 wk, pregnancies without folic acid supplementation were associated with GDM risk (adjusted odds ratio=6.70, 95% confidence interval: 1.22-36.77), while no significant association with folic acid supplementation dose >24 wk and GDM. No significant 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 <800 µg/d is the safe dose.

Relationship between gut microbiome characteristics and the effect of nutritional therapy on glycemic control in pregnant women with gestational diabetes mellitus.

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.