Exploring Preterm Birth as a Polymicrobial Disease: An Overview of the Uterine Microbiome

Abstract

Infection is a leading cause of preterm birth (PTB). A focus of many studies over the past decade has been to characterize microorganisms present in the uterine cavity and document any association with negative pregnancy outcome. A range of techniques have been used to achieve this, including microbiological culture and targeted polymerase chain reaction assays, and more recently, microbiome-level analyses involving either conserved, phylogenetically informative genes such as the bacterial 16S rRNA gene or whole shotgun metagenomic sequencing. These studies have contributed vast amounts of data toward characterization of the uterine microbiome, specifically that present in the amniotic fluid, fetal membranes, and placenta. However, an overwhelming emphasis has been placed on the bacterial microbiome, with far less data produced on the viral and fungal/yeast microbiomes. With numerous studies now referring to PTB as a polymicrobial condition, there is the need to investigate the role of viruses and fungi/yeasts in more detail and in particular, look for associations between colonization with these microorganisms and bacteria in the same samples. Although the major pathway by which microorganisms are believed to colonize the uterine cavity is vertical ascension from the vagina, numerous studies are now emerging suggesting hematogenous transfer of oral microbiota to the uterine cavity. Evidence of this has been produced in mouse models and although DNA-based evidence in humans appears convincing in some aspects, use of methodologies that only detect viable cells as opposed to lysed cells and extracellular DNA are needed to clarify this. Such techniques as RNA analyses and viability polymerase chain reaction are likely to play key roles in the clinical translation of future microbiome-based data, particularly in confined environments such as the uterus, as detection of viable cells plays a key role in diagnosis and treatment of infection.

Reproductive Microbiomes: Using the Microbiome as a Novel Diagnostic Tool for Endometriosis

“…The role of the microbiome in the uterus and cervix is largely unknown, but the implications for human health, reproduction, fertility, and the development of human fetuses are immense [31]. Consistent with other studies characterizing the uterine bacterial community using next generation sequencing, we demonstrated that the uterine bacterial community is comprised mostly of a Bacteroidetes core, with a large percentage of Firmicutes, specifically Lactobacillus sp.…”

“…It is becoming apparent that other key members of the microbiome like fungi and viruses may play a key role in human health and disease [31] and understanding these dynamics will be imperative if we are to improve these conditions. Future studies will characterize other members of the microbiome to understand how endometriosis alters these communities.…”

Neurogenetic Aspects of Perinatal Hypoxic-Ischemic Affections of the Central Nervous System

“…После того, как стало ясно, что полость матки не стерильна, как счи-талось ранее, а колонизирована самыми различными микроорганизмами, многие стали относить этот факт к причине преждевременных родов [40,41]. В связи с этим в настоящее время разрабатывается «гипотеза преждевременных родов как полимикробной болезни» [42]. В частности, такие бактерии, как Ureaplasma sр.…”

“…В частности, такие бактерии, как Ureaplasma sр. и Fusobacterium sp., обнаруживались в матке в значи-тельной степени при неблагоприятных исходах бере-менности [42]. Предположительно маточный микробиом может вызывать эпигенетические регуляции, приводя-щие к преждевременным родам.…”

Developing Research Priorities for Prediction and Prevention of Preterm Birth

“…Although multiple studies demonstrate that individual infectious agents and a community of infectious agents could contribute to SPTB, it remains unclear how these changes in microbiota cause SPTB. 6 Sequential changes in the microbiota during the pregnancy likely are important in either initiating inflammation or suppressing protective factors, resulting in rupture of membranes; however, our understanding of the role of microbiota in SPTB is rather limited. Therefore, research to characterize the entire microbiome present in vaginal and placental tissues is important and may lead to a better understanding of the role of bacteria in SPTB.…”