Gut bacterium Clostridium innocuum linked to higher risk of preterm birth, study finds

Researchers in China report that higher levels of the gut bacterium Clostridium innocuum are associated with an increased risk of preterm birth, and that the organism produces an enzyme capable of degrading estradiol, the most potent form of estrogen critical to pregnancy.

The study analyzed stool and blood samples from two large pregnancy cohorts in China, totaling more than 5,300 participants. In the Tongji‑Huaxi‑Shuangliu Birth cohort, stool samples were collected from 4,286 women in early pregnancy at an average of 10.4 gestational weeks. In the Westlake Precision Birth cohort, 1,027 participants provided stool samples in mid‑pregnancy, around 26 gestational weeks. Blood samples from all participants were used to assess human genetic variation and hormone metabolism.

Investigators found that women who delivered before 37 weeks of gestation were more likely to have higher levels of C. innocuum detectable as early as the first trimester. Follow‑up laboratory analyses indicated that the bacterial species produces an enzyme that degrades estradiol, potentially lowering maternal levels of the hormone. Estradiol supports uterine growth, maintains the uterine lining, helps regulate key pregnancy hormones and contributes to fetal organ development; low levels in early pregnancy have been associated with increased miscarriage risk.

"Estradiol regulates critical pathways that sustain pregnancy and initiate the process of childbirth," Zelei Miao of Westlake University, the study's first author, said in written comments accompanying the paper. The corresponding author, An Pan of Huazhong University of Science and Technology, noted that preterm birth remains a leading cause of death in newborns and children under five and suggested that monitoring the gut microbiome could help prevent adverse pregnancy outcomes.

The researchers also propose an immune mechanism. Pregnancy normally involves a degree of immune tolerance to prevent rejection of the fetus, but they said C. innocuum may trigger immune activation that contributes to preterm labor. The team emphasized that their analysis focused on associations between gut bacteria and preterm birth and did not assess links with other conditions.

Previous research has tied C. innocuum to chronic inflammation and cancer, and the authors observed that reduced estrogen could theoretically remove a protective anti‑inflammatory effect that estrogen has been reported to exert in colon cancer. The paper does not establish a causal relationship between the bacterium and cancer, but it raises questions about how interactions between the microbiome and hormone metabolism might influence health beyond pregnancy.

About one in 10 births worldwide is premature, and prematurity accounts for roughly 1 million child deaths annually, according to international public‑health estimates cited by the authors. Longer‑term studies have also linked preterm delivery with elevated maternal health risks; a U.S. study by the Icahn School of Medicine reported that women who deliver preterm have higher rates of all‑cause mortality in the decade following delivery, and those with extremely preterm births face still greater increased risks.

The study's authors cautioned that their findings derive from two China‑based cohorts with a relatively low prevalence of preterm birth, which may limit generalizability to other populations. They called for additional research to confirm the association in diverse groups, to clarify whether C. innocuum directly causes reductions in estradiol in humans, and to explore possible interventions.

The findings were published in the Cell Press journal Cell Host & Microbe. The authors said future work will examine how C. innocuum and related microbiome changes interact with estrogen signaling and immune function across the life course, with the goal of developing targeted strategies to reduce preterm birth risk.