Predicting the risk of preterm birth through vaginal microbiota
During pregnancy, the genetic structure of the bacterial population in the vaginal microbiota seems to follow a specific trajectory when gestation leads to preterm birth. Gardnerella spp. is believed to be a signature of preterm birth.
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Respiratory, gastrointestinal and neurodevelopmental complications:
birth before 37 completed weeks of gestation. There are sub-categories of preterm birth, based on gestational age:
- extremely preterm (less than 28 weeks);
- very preterm (between 28 and 32 weeks);
- moderate to late preterm (between 32 and 37 weeks). Source: WHO ) is the main cause of neonatal morbidity and mortality. The vaginal microbiota seems to be involved, but the underlying mechanisms remain poorly understood. This flora can change rapidly during gestation, due to hormonal changes, genital infections, antibiotics, etc. A team of researchers and clinicians from the states of New York and Virginia tracked the genome of the vaginal microbiota of 175 American women throughout their pregnancies (40 of whom subsequently experienced spontaneous preterm delivery, and 135 of whom delivered at full term).
Higher genetic diversity
The study shows that the two types of pregnancy differ in terms of vaginal microbiota composition: certain bacterial species of the Lactobacillus genus, such as L. helveticus, L. crispatus, L. gasseri and L. jensenii, are associated with full-term pregnancies, while Megasphaera genomosp, Gardnerella spp. and Atopobium vaginae are linked to preterm births.
Another finding is that the genetic diversity of the vaginal microbiota is higher in the first half of pregnancies that end preterm, due to Gardnerella species. More precisely, the (sidenote: Nucleotide diversity number of nucleotide differences for a given sequence for 2 individuals (here 2 bacteria) randomly selected in the population. ) of Gardnerella spp. increases at the start of pregnancies that end preterm - peaking at around 13 weeks of gestation, then returning to its initial value at around 20 weeks of gestation - whereas it remains stable in pregnancies that are carried to term. The genetic diversity of Gardnerella spp. during the first half of pregnancy therefore appears to affect pregnancy outcomes and could perhaps be used as a biomarker for the early diagnosis of preterm birth.
3.4 million infants born preterm (before 37 weeks of gestation are completed) in 2020.
900,000 deaths linked to preterm birth in 2019, the leading cause of death in children under five.
4% to 16% preterm births by 2020, depending on the country.
An adaptive evolution of Gardnerella
But how can we explain this peak in Gardnerella nucleotide diversity? Compared to other bacteria, Gardnerella shows a 1.5-fold higher growth rate at the start of pregnancy, more frequent
exchange of genetic information (DNA or RNA fragments in the case of certain viruses) to create new genetic combinations and thus new genomes, ensuring genetic admixture and the maintenance of a diversity that enables adaptation to any change in the environment.
and greater selection of mutations that benefit this bacterium (and increased elimination of deleterious mutations).
Antibiotics and other xenobiotics are thought to be involved. In fact, the more diversified gene pool of G. swidsinskii seems to correspond to an adaptation to drugs, confirming a previously suggested effect of xenobiotics in the vaginal environment; (sidenote: increased presence of phage-borne antibiotic resistance genes. ) .
From vaginal microbiota to the host
Genomic variation in vaginal bacteria is therefore believed to affect the host’s phenotypes (including pregnancy outcomes). However, the authors do not rule out another explanation, even if they consider it unlikely: the associations between microbial genetic diversity and pregnancy outcomes could also result from unmeasured confounding factors (drugs, chemical compounds, etc.) that might act on both variables.