How Gut Bacteria May Predict Preterm Birth

During pregnancy, expectant mothers often take steps to prepare for the arrival of their baby, such as taking vitamins and supplements and avoiding smoking or alcohol. While a typical pregnancy lasts about 40 weeks, preterm birth—defined as birth before 37 weeks of gestation—can occur and is the leading cause of neonatal and under-five mortality worldwide.¹

Although much research has focused on the vaginal microbiome and its potential connection to preterm birth, the role of the gut microbiome remains less understood. This gap in knowledge motivated a group of researchers in China to explore the maternal gut microbiome more closely and assess its potential link to preterm birth.

In a recent study, published in Cell Host & Microbe, the team identified maternal gut microbes associated with a higher risk of preterm birth during early pregnancy, especially those that can degrade estradiol, an important pregnancy hormone.² The researchers hope to further explore this association of estradiol-degrading bacteria as potential predictive biomarkers for preterm birth.

First, the researchers gathered stool and blood samples from two groups of pregnant women—one in early pregnancy and the other in mid-pregnancy. Using metagenome and 16S rRNA sequencing, the team identified similar gut microbiota profiles across the women. From this, they found five prevalent genera: Blautia, Faecalibacterium, Bacteroides, Anaerostipes, and Streptococcus. At the same time, they tracked each woman's preterm delivery status.

The researchers then turned to statistical models to dive deeper into the relationship between the gut microbiota and factors like gestational duration and preterm birth. Their analysis uncovered 11 specific genera linked to these outcomes, but one species stood out: Clostridium innocuum. This bacterium had the strongest connection to preterm birth.

Intrigued by C. innocuum, the team investigated its role in sex hormone metabolism and found that it makes an enzyme that degrades estradiol, a hormone important in pregnancy. To explore this further, they tested the bacterium’s estradiol degrading ability in female mice across different gestational periods (from early pregnancy to having a near-term fetus) and found that doses of C. innocuum significantly reduced estradiol levels by converting it into estrone. Additional analysis revealed key enzymes in the bacterium that played a critical role in this process.

Because of these findings, the researchers hypothesize that a high prevalence of C. innocuum may dysregulate estradiol levels and increase the risk of preterm birth. However, the team also acknowledged that scientists would need to evaluate more cohorts to validate these findings in broader populations.

“This study suggests that for pregnant women or women preparing to become pregnant, it may be important to monitor their gut microbiome to prevent potential adverse pregnancy outcomes,” said study coauthor An Pan, an epidemiologist at Huazhong University of Science and Technology in a press release.