Recent evidence has indicated that bacteria-derived extracellular vesicles (EVs) are important for host–microbe communication. The aims of the present study were to evaluate whether bacteria-derived EVs are excreted via the urinary tract and to compare the composition of bacteria-derived EVs in the urine of pregnant and non-pregnant women. Seventy-three non-pregnant and seventy-four pregnant women were enrolled from Dankook University and Ewha Womans University hospitals. DNA was extracted from urine EVs after EV isolation using the differential centrifugation method. 16S ribosomal RNA (16S rRNA) gene sequencing was performed using high-throughput 454 pyrosequencing after amplification of the V1–V3 region of the 16S rDNA. The composition of 13 taxa differed significantly between the pregnant and non-pregnant women. At the genus level, Bacillus spp. EVs were more significantly enriched in the urine of the pregnant women than in that of the non-pregnant women (45.61% vs 0.12%, respectively). However, Pseudomonas spp. EVs were more dominant in non-pregnant women than in pregnant women (13.2% vs 4.09%, respectively). Regarding the compositional difference between pregnant women with normal and preterm delivery, EVs derived from Ureaplasma spp. and the family Veillonellaceae (including Megasphaera spp.) were more abundant in the urine of preterm-delivered women than in that of women with normal deliveries. Taken together, these data showed that Bacillus spp. EVs predominate in the urine of pregnant women, whereas Pseudomonas spp. EVs predominate in the urine of non-pregnant women; this suggests that Bacillus spp. EVs might have an important role in the maintenance of pregnancy.

Yang DK, et al. Clin Exp Vaccine Res. 2017 Jul;6(2):111-119. https://doi.org/10.7774/cevr.2017.6.2.111

OBJECTIVE The objectives of this study were to compare early predictive marker of the metabolic syndrome with proopiomelanocortin (POMC) methylation status and to determine the association among birth weight, ponderal index, and cord blood methylation status. RESEARCH DESIGN AND METHODS We collected pregnancy outcome data from pregnant women, cord blood samples at delivery, and blood from children (7–9 years old; n = 90) through a prospective cohort study at Ewha Womans University, MokDong Hospital (Seoul, Korea), from 2003–2005. POMC methylation was assessed by pyrosequencing. We divided subjects into three groups according to cord blood POMC methylation: the low methylation (90th percentile) groups. We analyzed the association of POMC methylation status at birth with adiposity and metabolic components using ANCOVA and multiple linear regression analysis. RESULTS Birth weights (P = 0.01) and ponderal indices (P = 0.01) in the high POMC methylation group were significantly lower than in the mid-POMC methylation group. In terms of metabolic components of childhood, blood triglycerides (57.97, 67.29 vs. 113.89 mg/dL; P = 0.03, 0.01) and insulin (7.10, 7.64 vs. 10.13 μIU/mL; P = 0.05, 0.02) at childhood were significantly higher in the high POMC methylation group than in the low and mid-POMC methylation group. CONCLUSIONS High POMC methylation in cord blood was associated with lower birth weight, and children with high POMC methylation in cord blood showed higher triglycerides and higher insulin concentrations in blood. Thus, POMC methylation status in cord blood may be an early predictive marker of future metabolic syndrome.

Microbial infection of the placenta, amniotic fluid, vaginal canal, and oral cavity is known to significantly contribute to preterm birth (PTB). Although microbes can be translocated into the blood, little is known regarding the blood microbiota during pregnancy. To assess changes in the microbiome during pregnancy, blood samples were obtained 2 or 3 times during pregnancy from a cohort of 45 pregnant women enrolled between 2008 and 2010. To analyze the association with PTB, we conducted a case-control study involving 41 pregnant women upon admission for preterm labor and rupture of membrane (20 with term delivery; 21 with PTB). Bacterial diversity was assessed in number and composition between the first, second, and third trimesters in term delivered women according to 16S rRNA gene amplicon sequencing, and data were analyzed using Quantitative Insight Into Microbial Ecology (QIIME). Taxonomy was assigned using the GreenGenes 8.15.13 database. Dominant microorganisms at the phylum level in all pregnant women were identified as Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. However, the number and composition of bacteria in women with PTB differed from that in women with term delivery. Firmicutes and Bacteroidetes were more abundant in women with PTB than in women with term delivery, while Proteobacteria was less prevalent in women with PTB. At the genus level, Bacteroides, Lactobacillus, Sphingomonas, Fastidiosipila, Weissella, and Butyricicoccus were enriched in PTB samples. These observational results suggest that several taxa in the maternal blood microbiome are associated with PTB. Further studies are needed to confirm the composition of the blood microbiota in women with PTB. Additionally, the mechanism by which pathogenic microbes in maternal blood cause infection and PTB requires further analysis.

Introduction: Breast cancer is the second leading cancer in Korean women. To assess potential genetic associations between the prostate stem cell antigen (PSCA) gene in the chromosome 8q24 locus and breast cancer risk in Korean women, 13 SNPs were selected and associations with breast cancer risk were analyzed with reference to hormone receptor (HR) and menopausal status. Methods: We analyzed DNA extracted from buffy coat from 456 patients and 461 control samples, using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) based upon region-specific PCR followed by allele-specific single base primer extension reactions. Risks associated with PSCA genotypes and haplotypes were estimated with chi-square test (chi(2) -test), and polytomous logistic regression models using odds ratios (OR) and 95% confidence intervals (CIs), by HR and menopausal status. Results: In case-control analysis, odds ratios (OR) of rs2294009, rs2294008, rs2978981, rs2920298, rs2976395, and rs2976396 were statistically significant only among women with estrogen receptor (ER) negative cancers, and those of rs2294008, rs2978981, rs2294010, rs2920298, rs2976394, rs10216533, and rs2976396 were statistically significant only in pre-menopausal women, and not in postmenopausal women. Risk with the TTGGCAA haplotype was significantly elevated in ER (-) status (OR= 1.48, 95% CI= 1.03 similar to 2.12, p < 0.05). Especially risk of allele T of rs2294008 is significantly low in pre-menopausal breast cancer patients and AA genotype of rs2976395 in ER (-) status represents the increase of OR value. Conclusion: This report indicated for the first time that associations exist between PSCA SNPs and breast cancer susceptibility in Korean women, particularly those who are pre-menopausal with an estrogen receptor negative tumor status.

Gastric cancer is ranked as the most common cancer in Koreans. A recent molecular biological study about the folate pathway gene revealed the correlation with a couple of cancer types. In the folate pathway, several genes are involved, including methylenetetrahydrofolate reductase (MTHFR), methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), and methyltetrahydrofolate-homocysteine methyltransferase (MTR). The MTHFR gene has been reported several times for the correlation with gastric cancer risk. However, the association of the MTRR or MTR gene has not been reported to date. In this study, we investigated the association between the single nucleotide polymorphisms (SNPs) of the MTHFR, MTRR, and MTR genes and the risk of gastric cancer in Koreans. To identify the genetic association with gastric cancer, we selected 17 SNPs sites in folate pathway-associated genes of MTHFR, MTR, and MTRR and tested in 1,261 gastric cancer patients and 375 healthy controls. By genotype analysis, estimating odds ratios and 95% confidence intervals (CI), rs1801394 in the MTRR gene showed increased risk for gastric cacner, with statistical significance both in the codominant model (odds ratio [OR], 1.39; 95% CI, 1.04 to 1.85) and dominant model (OR, 1.34; 95% CI, 1.02 to 1.75). Especially, in the obese group (body mass index ≥ 25 kg/m(2)), the codominant (OR, 9.08; 95% CI, 1.01 to 94.59) and recessive model (OR, 3.72; 95% CI, 0.92 to 16.59) showed dramatically increased risk (p < 0.05). In conclusion, rs1801394 in the MTRR gene is associated with gastric cancer risk, and its functional significance need to be validated.