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.
Highlights
It has been well established that infection is a leading cause of preterm birth (PTB) and is highly associated with the deliveries that occur at the earliest gestations [1, 2]
Several theories have been proposed outlining the establishment of intra-uterine infections, the most widely accepted is that microorganisms residing in the vagina vertically migrate through the cervix, colonize the fetal membranes and subsequently, the amniotic fluid (AF), placenta, and fetus [1]
Studies have attempted to document these organisms, first using conventional microbiological culture and in the past two decades using a combination of culture, organismspecific polymerase chain reaction (PCR) assays and in the case of bacteria, 16S rDNA phylogenetics using a range of approaches including molecular cloning, denaturing gradient gel electrophoresis (DGGE), and terminal restriction fragment length polymorphism (TRFLP) analyses
Summary
It has been well established that infection is a leading cause of preterm birth (PTB) and is highly associated with the deliveries that occur at the earliest gestations [1, 2]. Studies have attempted to document these organisms, first using conventional microbiological culture and in the past two decades using a combination of culture, organismspecific polymerase chain reaction (PCR) assays and in the case of bacteria, 16S rDNA phylogenetics using a range of approaches including molecular cloning, denaturing gradient gel electrophoresis (DGGE), and terminal restriction fragment length polymorphism (TRFLP) analyses. These studies have contributed a wealth of information to our knowledge of what microorganisms colonize the uterine cavity. AMNIOTIC FLUID MICROBIOME Since the discovery of bacteria in the AF of cesarean section pregnancies by Harris and Brown in 1927 [6], the previously held www.frontiersin.org
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