Maternal gut microbiome composition may be linked to preterm births

Researchers have found that the presence of certain bacteria in the maternal gut microbiome during early pregnancy is linked to a higher risk of preterm birth. Publishing in the Cell Press journal Cell Host & Microbe on September 10, the study reports that one particular species, Clostridium innocuum (C. innocuum), contains a gene that can degrade estradiol—an important pregnancy hormone. 

“Preterm birth is a leading cause of death in newborns and children under five,” says corresponding author An Pan of Huazhong University of Science and Technology. “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.” 

The researchers used samples and data from two large pregnancy cohorts—the Tongji-Huaxi-Shuangliu Birth cohort from southwest China and the Westlake Precision Birth cohort from southeast China. 

For the first cohort, the team collected stool samples from 4,286 participants in early pregnancy, at an average of 10.4 gestational weeks. For the second cohort, they collected stool samples from 1,027 participants in mid-pregnancy, or around 26 gestational weeks. They also collected blood samples from all participants, which were used to measure human genetic variations and hormone metabolism.  

After working with the first cohort, the researchers were able to establish a comprehensive database containing rRNA-based microbial genera data, metagenome-based species data, and phenotype data such as preterm delivery status.  

“We used several statistical models to screen the annotated gut microbial genera and species and their relationship to preterm birth status or gestational duration,” says co-corresponding author Xiong-Fei Pan of Sichuan University in Chengdu, China. “Through that work, we identified 11 genera and 1 species that had a statistically significant link.” 

The results, which were validated with the second cohort, showed that bacterial species C. innocuum—a small, rod-shaped bacteria—had the strongest connection to preterm birth. Further study of C. innocuum revealed that this species makes an enzyme that degrades estradiol—a form of estrogen that plays a pivotal role during pregnancy. 

“Estradiol regulates critical pathways that sustain pregnancy and initiate the process of childbirth,” says first author Zelei Miao of Westlake University. “We propose that dysregulated estradiol levels induced by a high prevalence of C. innocuum could be the mechanism that links the gut microbiome to preterm birth.” 

The researchers note that because their study was based on two China-based cohorts with a relatively low prevalence of preterm birth, the findings may not be generalizable to other populations. In the future, they hope to further elucidate the molecular mechanisms by which C. innocuum modulates preterm birth risk and potentially identify optimal intervention strategies to mitigate the bacteria’s impact on pregnancy. They also seek to characterize the interaction between C. innocuum and host estrogen metabolism more generally, beyond pregnancy. 

“We have discovered robust gut microbiome features that appear to predict the risk of preterm birth,” says corresponding author Ju-Sheng Zheng of Westlake University. “This interplay among host genes, the gut microbiome, and pregnancy outcomes has never been reported before.” 

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This work was supported by funding from the National Key R&D Program of China, the ‘‘Pioneer’’ and ‘‘Leading goose’’ R&D Program of Zhejiang, the National Natural Science Foundation of China, the Zhejiang Provincial Key Laboratory Construction Project of China, the Zhejiang Provincial Natural Science Foundation of China, and the Research Program of Westlake Laboratory of Life Sciences and Biomedicine.  

Cell Host & Microbe, Miao et al., “Maternal gut microbiome during early pregnancy predicts preterm birth” https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(25)00330-0

Cell Host & Microbe (@cellhostmicrobe), published by Cell Press, is a monthly journal that publishes novel findings and translational studies related to microbes (which include bacteria, fungi, parasites, and viruses). The unifying theme is the integrated study of microbes in conjunction and communication with each other, their host, and the cellular environment they inhabit. Visit http://www.cell.com/cell-host-microbe. To receive Cell Press media alerts, contact press@cell.com.