Sources of the Placental Microbiome in Full-term, Pre-term, and Pre-eclampsia
Loading...
Date
2022-03
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Objective: In the US, pre-term birth affects 1 in 9 babies and pre-eclampsia occurs in 3-8% of pregnancies. While the cause of pre-eclampsia is unknown, placental dysfunction caused by angiogenic imbalances and inflammatory disturbances plays a role. Previous research in the lab has shown that disturbances to the microbiome may also cause an upregulation in inflammatory markers. Therefore, we thought that dysbiosis in the microbiome may be a factor in inflammation that leads to adverse pregnancy outcomes. We aimed to investigate whether the oral microbiome has a role in contributing to pre-term delivery or pre-eclampsia. Methods: Saliva, plaque, serum, and placental samples were collected from 130 women (45 healthy, 36 with pre-eclampsia, and 49 who delivered pre-term). DNA was isolated and underwent whole genome sequencing. Taxonomy was assigned using Kraken against the Human Oral Microbiome Database (HOMD). Multiple bioinformatic tools were used to analyze the sequencing data: Prodigal, DIAMOND, and MEGAN were used to read, translate, and determine gene identity and function as indicated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the Comprehensive Antibiotic Resistance Database (CARD), and the Virulence Factor Database (VFDB). SourceTracker quantified the contributions of the salivary, plaque, and serum biomes to the placental biome. ALDEx2 determined differential species abundance and sparce partial least squares discriminant analysis (sPLS-DA) revealed the primary drivers of separation seen within the placental samples. Results: All placental samples in the study demonstrated the presence of a microbiome and the composition of the microbiome did not differ between mode of delivery, vaginal or c-section (p-value=0.973, Aitchison distance, PERMANOVA). However, placental samples demonstrated significant beta dispersion in all three groups functionally. This was not observed in sequences of salivary or serum origin. Principle component analysis of Aitchison distance revealed clustering of the placental microbiome based on pregnancy outcome, both taxonomically and functionally (p-value=0.001 for both, PERMANOVA). sPLS-DA demonstrated that placental levels of B. subtilis was an indicator of a healthy pregnancy outcome while L. crispatus indicated pre-term, and C. matruchotii indicated pre-eclampsia. Many metabolism-associated genes, such as type I restriction enzyme and transcription-repair coupling factor, and a disease associated gene, GTP-binding protein LepA, were also indicators of pre-eclampsia. SourceTracker revealed that saliva was the predominant source of microorganisms in serum in all three groups. SourceTracker also revealed serum to be the predominant source of the placental biome. In mothers with pre-eclampsia, saliva was an additional source of the placenta's biome. Conclusion: The oral microbiome is a source of the placental microbiome and the translocation of certain oral species to the placenta via the serum is associated with pre-term delivery and pre-eclampsia. Promoting healthy oral bacteria in a mother may therefore help reduce her risk of adverse pregnancy complications. Little things like taking care of mom's oral health have a big impact on the mother's health as well as her child's. In subsequent studies, we would like to determine whether the gut microbiome also plays a role as microorganisms may be able to translocate if the woman is suffering from "leaky gut" syndrome as other labs have shown that early onset pre-eclampsia is associated with gut microbiome changes.
Description
Health Sciences: 3rd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
Keywords
microbiome, pregnancy, placenta, pre-eclampsia, pre-term