Understanding how maternal diet affects in utero neonatal gut microbiota and epigenetic regulation may provide insight into disease origins and long-term health. The impact of Mediterranean diet pattern adherence (MDA) on fetal gut microbiome and epigenetic regulation was assessed in 33 pregnant women. Participants completed a validated food frequency questionnaire in each trimester of pregnancy; the alternate Mediterranean diet (aMED) score was applied. Umbilical cord blood, placental tissue, and neonatal meconium were collected from offspring. DNA methylation patterns were probed using the Illumnia EPICarray Methylation Chip in parturients with high versus low MDA. Meconium microbial abundance in the first 24 h after birth was identified using 16s rRNA sequencing and compared among neonates born to mothers with high and low aMED scores. Twenty-one mothers were classified as low MDA and 12 as high MDA. Pasteurellaceae and Bacteroidaceae trended towards greater abundance in the high-MDA group, as well as other short-chain fatty acid-producing species. Several differentially methylated regions varied between groups and overlapped gene regions including NCK2, SNED1, MTERF4, TNXB, HLA-DPB, BAG6, and LMO3. We identified a beneficial effect of adherence to a Mediterranean diet on fetal in utero development. This highlights the importance of dietary counseling for mothers and can be used as a guide for future studies of meconium and immuno-epigenetic modulation.

In utero colonization or deposition of beneficial microorganisms and their by-products likely occurs through various mechanisms, such as hematogenous spread or ascension from the reproductive tract. With high-throughput sequencing techniques, the identification of microbial components in first-pass neonatal meconium has been achieved. While these components are low-biomass and often not abundant enough to culture, the presence of microbial DNA signatures may promote fetal immune tolerance or epigenetic regulation prior to birth. The aim of this study was to investigate the maternal source of the neonatal first-pass meconium microbiome. Maternal vaginal and anal samples collected from twenty-one maternal–infant dyad pairs were compared via principal component analysis to first-pass neonatal meconium microbial compositions. Results demonstrated the greatest degree of similarity between the maternal gut microbiome in the second and third trimesters and vaginal microbiome samples across pregnancy, suggesting that the maternal gut microbiota may translocate to the fetal gut during pregnancy. This study sheds light on the origin and timing of the potential transfer of maternal microbial species to offspring in utero.

Background: Vaginal Lactobacillus predominance is associated with improved vaginal health and reduced pregnancy complications. Little is known about how dietary quality may improve vaginal microbial composition or about dietary interventions that may promote Lactobacillus abundance. To understand the host factors affecting vaginal microbiota during pregnancy in a multi-ethnic cohort in Hawai`i. We hypothesize that better diet quality improves vaginal microbial composition, as represented by Lactobacillus abundance and depletion of anaerobic organisms. Methods: We compared comprehensive diet quality, as measured by the Healthy Eating Index-2015 (HEI-2015), to taxonomic classifications of bacteria present within the vagina. Participants of the four predominant ethnic groups in Hawai’i (Japanese, Filipino, Non-Hispanic White and Native Hawaiian) completed Quantitative Food Frequency Questionnaires (QFFQs) and collected vaginal swabs during each trimester. 16s rRNA amplicon sequencing (V2–V9 regions) was performed on vaginal samples. HEI-2015 scores and macro- and micronutrient intake were compared with the predominant species present using the Mann–Whitney-U test, PERMANOVA, and the Pearson correlation coefficient. A mixed-effects logistics regression model was used to predict the depletion of Lactobacillus species while accounting for confounding demographic factors. Results: Matched, longitudinal data for 40 participants demonstrated three predominant Lactobacillus species: L. crispatus, L. iners, and L. gasseri, with another subset of samples with anaerobic abundance. (Primarily, Atopobium vaginae, Prevotella, and Gardnerella vaginalis.) Non-Hispanic White participants had lower amounts of Lactobacillus iners compared to other racial and ethnic groups. HEI scores correlated with the chao index and observed species number primarily in the first trimester (r = 0.25, p < 0.05). Greater carbohydrate intake was associated with a higher abundance of L. crispatus, while lower carbohydrate intake trended towards more L. iners (0.056) and anaerobic species. Conclusions: Increased carbohydrate consumption and improved diet quality may be associated with beneficial vaginal microbial composition in pregnancy.

Currently no recommendation exists to collect genital culture for Chlamydia trachomatis and Neisseria gonorrhoeae at diagnosis of spontaneous abortion. A retrospective cross sectional study was performed to identify first trimester abortions with concurrent genital culture collection in an emergency room setting. The results were compared to most current 2015 Center for Disease Control (CDC) statistics. Among women aged 15-24 the rate of C. trachomatis was increased to 20.0% and greater than CDC rate of 6.7% (RR 2.97, p<0.0001). No positive screens for C. trachomatis were found above age 30 and the study rate of N. gonorrhoeae was not significantly elevated. Younger women presenting for miscarriage have high prevalence of C. trachomatis in comparison to 2015 CDC statistics. Routine genital culture could be recommended at diagnosis of first trimester spontaneous abortion.

Objective: Bisphenol A and phthalate are known endocrine disruptors and capable of inducing epigenetic changes in the human population. However, their impact on the placenta is less well studied. Our objective was to measure the effect of exposure to bisphenol A and benzyl butyl phthalate in first-trimester HTR8-SVneo and third-trimester 3A-sub E trophoblast cells by profiling the DNA methylation pattern of the imprinting control region of the IGF2 (insulin-like growth factor) and H19 genes. Methods: Human placental HTR8-SVneo and 3A-sub E cell lines were treated with two sub-lethal concentrations of bisphenol A and benzyl butyl phthalate. Demethylating agent, 5-azacytidine, was used as a positive control. Cells were harvested on post-treatment days 1 and 4. The methylation profile of six CpG dinucleotide sites, part of the CTCF 6 binding site of the IGF2/H19 imprinting control region, was determined by pyrosequencing. Results: In the first-trimester HTR8-SVneo cell line, we observed a significant increased methylation of the CpG sites 3, 4 when treated with a high concentration of bisphenol A or benzyl butyl phthalate while increased methylation at site 6 for both high and low dose treatment on day 4. Demethylation of the CpG sites 1, 4, and 6 was observed when treated with 5-azacytidine on day 4. In the third-trimester 3A-sub E cell line, no significant changes in the methylation profile were observed under any treatment conditions. Conclusions: The results of this study demonstrate the capability of epigenetic changes in human placenta cells induced by bisphenol A and benzyl butyl phthalate. The observed methylation changes only in the first-trimester HTR8-SVneo cells phthalate may reflect a window of epigenetic susceptibility related to these environmental toxicants.