The effect of dietary fiber supplement on prevention of gestational diabetes mellitus in women with pre-pregnancy overweight/obesity: A randomized controlled trial.

Objective: To investigate the effect of dietary fiber intake during pregnancy on the prevention of gestational diabetes mellitus (GDM) in women who are overweight/obese prior to pregnancy. Methods: This randomized controlled trial was conducted in Shanghai General Hospital from June 2021 to March 2022. A total of 98 women who reported BMI≥24 kg/m2 prior to pregnancy were recruited before their 20th gestational week, and randomly (simple random allocation) assigned to the fiber supplement group (12 g of dietary fiber power twice daily) and the control group (standard prenatal care) from 20 to 24+6 gestational weeks. Both groups received nutrition education and dietary advice during the study. GDM diagnosis was performed by an oral glucose tolerance test (OGTT) at 25-28 weeks' gestation. Data are presented as means with SD, as medians with IQR, or as counts with percentages as appropriate. Comparisons were conducted using a t-test, Mann-Whitney U test, and χ2 test, respectively. Results: The incidence of GDM was significantly reduced in the fiber supplement group compared with the control group: 8.3 vs. 24.0% (χ2 = 4.40, p = 0.036). At OGTT, the mean fasting plasma glucose in the fiber supplement group was significantly lower than before the intervention (4.57 ± 0.38 mmol/L vs. 4.41 ± 0.29 mmol/L, p < 0.01) but not in the control group (4.48 ± 0.42 mmol/L vs. 4.37 ± 0.58 mmol/L, p = 0.150). Compared with the control group, the TG and TG/HDL-C ratio levels in the intervention group were significantly higher than those in the control group (2.19 ± 0.54 mmol/L vs. 2.70 ± 0.82 mmol/L and 1.19 ± 0.49 vs.1.63 ± 0.63, respectively, all P＜0.05). The body weight gain was significantly lower in the fiber supplement group than the control group (1.99 ± 1.09 kg vs. 2.53 ± 1.20kg, p = 0.022). None of the women randomized to the fiber supplement group experienced preterm birth (<37 weeks gestation) compared with 12.0% in the control group (p = 0.040). Excessive weight gain (total weight gain >11.5 kg for overweight, and >9.0 kg for obesity) occurred in 46.7% of women in the fiber supplement group compared with 68.0% in the control group (p = 0.035). There were no differences in other maternal and neonatal outcomes. Conclusion: Increased dietary fiber intake in pregnant women who were overweight/obese prior to pregnancy may reduce the risk of GDM, excessive weight gain, and preterm birth, but it did not improve blood lipids.

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.

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.

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.

Cav-1 participates in the development of diabetic neuropathy pain through the TLR4 signaling pathway.

This study aims to determine whether caveolin-1 (Cav-1) participates in the process of diabetic neuropathic pain by directly regulating the expression of toll-like receptor 4 (TLR4) and the subsequent phosphorylation of N-methyl-D-aspartate receptor 2B subunit (NR2B) in the spinal cord. Male Sprague-Dawley rats (120-150 g) were continuously fed with high-fat and high-sugar diet for 8 weeks, and received a single low-dose of intraperitoneal streptozocin injection in preparation for the type-II diabetes model. Then, these rats were divided into five groups according to the level of blood glucose, and the mechanical withdrawal threshold and thermal withdrawal latency values. The pain thresholds were measured at 3, 7, and 14 days after animal grouping. Then, eight rats were randomly chosen from each group and killed. Lumbar segments 4-6 of the spinal cord were removed for western blot analysis and immunofluorescence assay. Cav-1 was persistently upregulated in the spinal cord after diabetic neuropathic pain in rats. The downregulation of Cav-1 through the subcutaneous injection of Cav-1 inhibitor daidzein ameliorated the pain hypersensitivity and TLR4 expression in the spinal cord in diabetic neuropathic pain (DNP) rats. Furthermore, it was found that Cav-1 directly bound with TLR4, and the subsequent phosphorylation of NR2B in the spinal cord contributed to the modulation of DNP. These findings suggest that Cav-1 plays a vital role in DNP processing at least in part by directly regulating the expression of TLR4, and through the subsequent phosphorylation of NR2B in the spinal cord.

Mechanism of the JAK2/STAT3-CAV-1-NR2B signaling pathway in painful diabetic neuropathy.

PURPOSE: The aim of the present study was to further elucidate the role of JAK2/STAT3-CAV-1-NR2B on painful diabetic neuropathy. METHODS: In vivo, the mechanical withdrawal threshold and thermal withdrawal latency were measured to evaluate neuropathic pain behaviors (n= 8), while western blot (n= 5) and an immunofluorescence double staining experiment (n= 6) were performed to understand the molecular mechanism. In vitro, the individual culture of BV2 mouse microglia cell lines, the co-culture of BV2 mouse microglia cell lines and PC12 rat neuron cell lines, and western blot analysis were performed to understand the molecular mechanism between microglia and neurons. RESULTS: The expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B was upregulated in the dorsal horn of DNP rats throughout the experiment. Through the immunofluorescence double staining experiment, it was found that p-STAT3 was mainly expressed in activated microglia, and this condition can be stably maintained for approximately 2 weeks after the establishment of the DNP model. The intrathecal injection of JAK2 inhibitor AG490 can relieve the abnormal expression of p-JAK2, p-STAT3, t-CAV-1, and p-NR2B, and relieve pain. The remission of AG490 began on the third day, and it could be stably sustained for 14 days. In vitro high-glucose induced the activation of p-STAT3 in microglia, thereby upregulating the expression of p-CAV-1 and p-NR2B in neurons in the co-culture system. JAK2 inhibitor AG490 can alleviate the abnormal expression of these proteins in the JAK2/STAT3-CAV-1-NR2B signaling pathway in vitro. CONCLUSIONS: Microglial JAK2/STAT3 signaling probably contributes to neuropathic pain by activating the CAV-1-NR2B pathway.