Supplementary Material for: Polymorphisms in Genes Coding for Cytokines, Mannose-Binding Lectin, Collagen Metabolism and Thrombophilia in Women with Cervical Insufficiency

Objective: To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 (MBL2), collagen1α1 (COL1A1), factor II and factor V Leiden genes. Methods: In a case-control study, potential maternal biomarkers for cervical insufficiency were investigated in 30 women with a history of second-trimester miscarriage or preterm birth due to cervical insufficiency and in 70 control women. Results: Homozygous carriers of the interleukin 6 (IL6) -174 genotype GG had an odds ratio (OR) of 3.1 [95% confidence interval (95% CI) 1.3-7.4, p = 0.01] and MBL2 genotypes coding for low or intermediate levels of plasma MBL had an OR of 3.3 (95% CI 1.2-9.0, p = 0.01) for cervical insufficiency compared with controls. Serum MBL levels were lower in women with cervical insufficiency than in controls (median 408 and 1,985 ng/ml, respectively, p < 0.01). Conclusions: Single nucleotide polymorphisms in the IL6 gene and the MBL2 gene and low MBL levels related to the latter polymorphism may increase the risk of preterm birth due to cervical insufficiency

Supplementary Material for: Polymorphisms in Genes Coding for Cytokines, Mannose-Binding Lectin, Collagen Metabolism and Thrombophilia in Women with Cervical Insufficiency

Objective: To study the association between cervical insufficiency and single nucleotide polymorphisms in seven genes coding for pro- and anti-inflammatory cytokine-related factors, mannose-binding lectin 2 (MBL2), collagen1α1 (COL1A1), factor II and factor V Leiden genes. Methods: In a case-control study, potential maternal biomarkers for cervical insufficiency were investigated in 30 women with a history of second-trimester miscarriage or preterm birth due to cervical insufficiency and in 70 control women. Results: Homozygous carriers of the interleukin 6 (IL6) -174 genotype GG had an odds ratio (OR) of 3.1 [95% confidence interval (95% CI) 1.3-7.4, p = 0.01] and MBL2 genotypes coding for low or intermediate levels of plasma MBL had an OR of 3.3 (95% CI 1.2-9.0, p = 0.01) for cervical insufficiency compared with controls. Serum MBL levels were lower in women with cervical insufficiency than in controls (median 408 and 1,985 ng/ml, respectively, p < 0.01). Conclusions: Single nucleotide polymorphisms in the IL6 gene and the MBL2 gene and low MBL levels related to the latter polymorphism may increase the risk of preterm birth due to cervical insufficiency

Additional file 1: of Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum

Figure S1. Flow chart. Figure S2. Bristol stool scale and bowel movement frequency in women with and without GDM during pregnancy. Figure S3. Bristol stool scale and bowel movement frequency postpartum in women with and without previous GDM. Figure S4. Third trimester alpha diversity. Figure S5. Relationship between glycaemic traits and alpha diversity. Figure S6. Phylum level composition in pregnant women with gestational diabetes and with normal glucose regulation. Figure S7. Family-level composition in pregnant women with gestational diabetes and with normal glucose regulation. Figure S8. Genus-level composition in pregnant women with gestational diabetes and with normal glucose regulation. Figure S9. Bacterial operational taxonomic units associated with glycaemic traits during pregnancy. Figure S10. Bacterial operational taxonomic units associated with glycaemic traits during pregnancy adjusted for pre-pregnancy BMI. Figure S11. Frequency of pre-pregnancy overweight and obesity according to GDM status. Figure S12. Taxonomic biomarkers of overweight and obesity. Figure S13. Operational taxonomic units differentially abundant in pregnant women with normal and above normal pre-pregnancy body mass index. Figure S14. Operational taxonomic units differentially abundant in pregnant women with GDM and normal glucose regulation adjusted for pre-pregnancy BMI. Figure S15. Relationship between glycaemic traits and alpha diversity adjusted for pre-pregnancy BMI. (PDF 3075 kb

Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum

Abstract Background Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum. Methods Gut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy. Results Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy. Conclusion GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits

Additional file 2: of Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum

Table S1. Supplementary third trimester characteristics between pregnant women with GDM and normoglycaemic pregnant women. Table S2. Indications for OGTT. Table S3. Supplementary descriptive postpartum. Table S4. Nutrient intake during pregnancy and postpartum. Table S5. Operational taxonomic units differentially abundant in women with and without gestational diabetes during pregnancy and postpartum. Table S6. Operational taxonomic units associated with glycaemic traits in pregnant women independent of GDM status and unadjusted for pre-pregnancy BMI. Table S7. Higher order taxa associated with high sensitivity CRP. Table S8. OTUs associated with high-sensitivity C-reactive protein in laten pregnancy and postpartum. Table S9. Spearman correlations between GDM discriminant taxa and pre-pregnancy BMI. Table S10. Operational taxonomic units differentially abundant in overweigt (n = 67) and obese women (n = 58) compared with lean women (n = 61). Table S11. Operational taxonomic units differentially abundant in women with and without gestational diabetes with available pre-pregnancy BMI. Table S12. Operational taxonomic units associated with weight gain during pregnancy adjusted for pre-pregnancy BMI and gestational age. Table S13. Higher order taxa associated with gestational weight gain. Table S14. OTUs exhibiting differential change from the third trimester to postpartum dependent on GDM status. Table S15. Higher order taxa exhibiting differential change from the third trimester to postpartum dependent on GDM status. (XLSX 152 kb

Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum

Abstract Background Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum. Methods Gut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy. Results Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy. Conclusion GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits