Alterations of gut microbiota in gestational diabetes patients during the second trimester of pregnancy in the Shanghai Han population.

BACKGROUND: The causes of gestational diabetes mellitus (GDM) are still unclear. Recent studies have found that the imbalance of the gut microbiome could lead to disorders of human metabolism and immune system, resulting in GDM. This study aims to reveal the different gut compositions between GDM and normoglycemic pregnant women and find the relationship between gut microbiota and GDM. METHODS: Fecal microbiota profiles from women with GDM (n = 21) and normoglycemic women (n = 32) were assessed by 16S rRNA gene sequencing. Fasting metabolic hormone concentrations were measured using multiplex ELISA. RESULTS: Metabolic hormone levels, microbiome profiles, and inferred functional characteristics differed between women with GDM and healthy women. Additionally, four phyla and seven genera levels have different correlations with plasma glucose and insulin levels. Corynebacteriales (order), Nocardiaceae (family), Desulfovibrionaceae (family), Rhodococcus (genus), and Bacteroidetes (phylum) may be the taxonomic biomarkers of GDM. Microbial gene functions related to amino sugar and nucleotide sugar metabolism were found to be enriched in patients with GDM. CONCLUSION: Our study indicated that dysbiosis of the gut microbiome exists in patients with GDM in the second trimester of pregnancy, and gut microbiota might be a potential diagnostic biomarker for the diagnosis, prevention, and treatment of GDM.

Association of gestational hypertriglyceridemia, diabetes with serum ferritin levels in early pregnancy: a retrospective cohort study.

Aims: Previous studies showed conflicting results linking body iron stores to the risk of gestational diabetes mellitus (GDM) and dyslipidemia. We aim to investigate the relationship between serum ferritin, and the prevalence of GDM, insulin resistance (IR) and hypertriglyceridemia. Methods: A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in the retrospective cohort study conducted. The participants were divided into four groups by quartiles of serum ferritin levels (Q1-4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across Sfer quartiles. Results: Compared with the lowest serum ferritin quartile (Q1), the ORs for Q3, and Q4 in our population were 1.79 (1.01-2.646), and 2.07 (1.089-2.562) respectively and this trend persisted even after adjusted for age and pre-BMI. Women with higher serum ferritin quartile including Q3 (OR=2.182, 95%CI=1.729-5.527, P=0.003) and Q4(OR=3.137, 95%CI=3.137-8.523, P<0.01)are prone to develop insulin resistance disorders. No significant difference was observed between sFer concentrations and gestational hypertriglyceridemia(GTG) in the comparison among these 4 groups across logistic regressions but TG was found positively correlated with increased ferritin values in the second trimester. Conclusions: Increased concentrations of plasma ferritin in early pregnancy are significantly and positively associated with insulin resistance and incidence of GDM but not gestational dyslipidemia. Further clinical studies are warranted to determine whether it is necessary to encourage pregnant women to take iron supplement as a part of routine antenatal care.

Associations of Thyroid Function Tests with Lipid Levels and Adverse Pregnancy Outcomes During the First Trimester.

Objective: The present study aims to evaluate the relationship of thyroid function during the first trimester of pregnancy with lipid levels and pregnancy outcomes. Methods: Women who delivered babies at the Shanghai General Hospital between March 2019 and December 2019 with a known pregnancy outcome and complete data were included in the present study (n = 1779). A retrospective cohort study of all subjects with available first-trimester thyroid function testing and lipid levels data was conducted, and the relationship of thyroid function with lipid levels and pregnancy outcomes was evaluated. The data were analyzed using the SPSS software for statistical correlation. Results: The proportion of caesarean sections was higher in women with hypothyroxinemia (HIA) and hypothyroidism than in women with euthyroidism. Hypothyroidism was shown to be related with polyhydramnios, preterm labor and hypertriglyceridemia. HIA was correlated with increased rates of gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension and hypertriglyceridemia. Compared with the euthyroidism group, the hypothyroidism group had a higher apolipoprotein A1 (Apo A1) level and apolipoprotein B level; the subclinical hypothyroidism group had a higher total cholesterol (TC) level and low-density lipoprotein cholesterol level; the HIA group had higher triglyceride, high-density lipoprotein cholesterol levels and lower TC, Apo A1 levels. TC levels were positively correlated with the thyroid-stimulating hormone level and negatively correlated with free thyroxine (FT4) level, and free triiodothyronine and FT4 levels were positively correlated with GDM occurrence. Conclusion: Thyroid function in early pregnancy is associated with dyslipidemia and pregnancy outcomes; conventional screening of thyroid diseases in early pregnancy may help improve lipid levels and decrease adverse pregnancy outcomes.

The characteristics of intestinal flora in overweight pregnant women and the correlation with gestational diabetes mellitus.

OBJECTIVE: To investigate the characteristics of intestinal flora in overweight pregnant women and the correlation with gestational diabetes mellitus (GDM). METHODS: A total of 122 women were enrolled and divided into four groups according to their pre-pregnancy BMI and the presence of GDM: group 1 (n = 71) with a BMI <24 kg/m2, without GDM; group 2 (n = 27) with a BMI <24 kg/m2, with GDM; group 3 (n = 17) with a BMI ≥24 kg/m2, without GDM; and group 4 (n = 7) with a BMI ≥24 kg/m2 with GDM. Feces were collected on the day that the oral glucose tolerance test was conducted. The V3-V4 variable region of 16S rRNA was sequenced using the Illumina Hiseq 2500 platform, and a bioinformatics analysis was conducted. RESULTS: There were differences between the four groups in the composition of intestinal flora, and it was significantly different in group 4 than in the other three groups. Firmicutes accounted for 36.4% of the intestinal flora in this group, the lowest among the four groups, while Bacteroidetes accounted for 50.1%, the highest among the four groups, making ratio of these two bacteria approximately 3:5, while in the other three groups, this ratio was reversed. In women with a BMI <24 kg/m2, the insulin resistance index (homeostatic model assessment for insulin resistance (HOMA-IR)) in pregnant women with GDM was higher than in those without (P3 = 0.026). CONCLUSION: The composition of the intestinal flora of pregnant women who were overweight or obese before pregnancy and suffered from GDM was significantly different than women who were not overweight or did not suffer from GDM.

Effect of exposure to antibiotics on the gut microbiome and biochemical indexes of pregnant women.

INTRODUCTION: Exposure to antibiotics (ABX) during pregnancy can have a systematic effect on both fetal and maternal health. Although previous biomonitoring studies have indicated the effects on children of extensive exposure to ABX, studies on pregnant women remain scarce. To explore the effect on pregnant women of environmental exposure to ABX through accidental ingestion and identify potential health risks, the present study investigated 122 pregnant women in East China between 2019 and 2020. RESEARCH DESIGN AND METHODS: The presence of six categories of ABX (quinolones, sulfonamides, lincosamides, tetracyclines, amide alcohol ABX, and ß-lactams) in plasma samples taken from the pregnant women was investigated using an ABX kit and a time-resolved fluorescence immunoassay. RESULTS: All six ABX were detected in the plasma, with a detection rate of 17.2%. It was discovered that the composition of intestinal flora in pregnant women exposed to ABX was different from that of pregnant women who had not been exposed to ABX. The intestinal flora of pregnant women exposed to ABX also changed at both the phylum and genus levels, and several genera almost disappeared. Furthermore, the metabolic levels of glucose and insulin and the alpha diversity of pregnant women exposed to ABX were higher than those of pregnant women not exposed to ABX. CONCLUSION: Pregnant women are potentially at higher risk of adverse microbial effects. Glucose metabolism and insulin levels were generally higher in pregnant women exposed to ABX than in unexposed women. Also, the composition and color of the gut microbiome changed.

LGR5 promotes epithelial ovarian cancer proliferation, metastasis, and epithelial-mesenchymal transition through the Notch1 signaling pathway.

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) plays a vital role in the development of malignant tumors; however, its biological role and underlying mechanism in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to investigate the biological function and clinical significance of LGR5 in human EOC. We evaluated LGR5 expression in EOC cell lines and tissues from ovarian cancer patients by qPCR, Western blotting, and immunohistochemical analysis. Cell proliferation, colony formation, transwell invasion assay, and scratch-wound assays were conducted to evaluate the expansion and invasion abilities of EOC cells. Tumor xenograft experiments were performed in female BALB/c athymic nude mice to test cell proliferation in vivo. Western blot analysis was performed to confirm the expression of epithelial-to-mesenchymal transition (EMT) signature proteins and their association with Notch1 signaling. The results demonstrated that LGR5 was overexpressed in EOC tissues and cell lines. Aberrant expression of LGR5 was significantly associated with patient age (P = 0.006), tumor histologic type (P < 0.001), and distant metastasis (P = 0.025). Consistent with these findings, suppression of LGR5 expression led to decreased proliferation and metastasis of EOC cell lines. Furthermore, LGR5 could induce EMT and regulate the Notch1 signaling pathway. Taken together,LGR5 may have an important role in the promotion of tumorigenesis and metastasis of EOC and is a potential therapeutic target for EOC management.

GOLPH3 induces epithelial-mesenchymal transition via Wnt/ß-catenin signaling pathway in epithelial ovarian cancer.

Golgi phosphoprotein 3 (GOLPH3), a newly recognized oncogene, is associated with tumor growth, metastasis, and poor prognosis in several types of cancer. However, its biological role and underlying mechanism in epithelial ovarian cancer (EOC) remain poorly understood. Here, we found that GOLPH3 was overexpressed in EOC tissues and cell lines. This overexpression promoted the migration and invasion of EOC cells. Moreover, GOLPH3 upregulated the expression of epithelial-mesenchymal transition (EMT) markers, such as N-cadherin and Snail, and the Wnt/ß-catenin-related genes cyclin-D1 and c-Myc, which were restored via silencing of GOLPH3 expression. Furthermore, the inhibitor and activator of the Wnt/ß-catenin pathway, XAV939 and LiCl, enhanced or decreased, respectively, the effect of GOLPH3 on EMT, which further confirmed that GOLPH3 promoted EMT progression via activation of Wnt/ß-catenin signaling. In addition, we found that EDD, the human hyperplastic discs gene, was consistent with GOLPH3 expression and also promoted the EMT process and activated Wnt/ß-catenin signaling. These findings demonstrate that EDD might be a downstream factor of GOLPH3. Taken together, our findings demonstrate the existence of a GOLPH3-Wnt/ß-catenin-EMT axis in EOC and provide a new therapeutic target to treat EOC.