Gut bacterium linked to cancer associated with higher risk of preterm birth, study finds

Researchers in China report an association between a gut bacterium previously linked to cancer and an increased risk of preterm birth, and identify a potential biological mechanism involving the hormone estradiol.

Analysis of stool and blood samples from more than 5,300 pregnant women found that higher levels of the bacterial species Clostridium innocuum in the maternal gut were more common among those who delivered before 37 weeks. In laboratory work reported alongside the population analysis, the team said C. innocuum produces an enzyme that degrades estradiol, the most potent form of estrogen that supports uterine growth, maintains the uterine lining and helps regulate fetal development.

The study pooled data from two pregnancy cohorts in China: the Tongji-Huaxi-Shuangliu Birth cohort in southwest China and the Westlake Precision Birth cohort in southeast China. Investigators collected stool samples from 4,286 participants in early pregnancy (average 10.4 gestational weeks) and from 1,027 participants in mid-pregnancy (around 26 weeks). Blood samples were used to assess human genetic variation and hormone metabolism. Preterm birth was defined as delivery before 37 completed weeks of gestation.

The authors report that women who went on to deliver preterm exhibited higher gut levels of C. innocuum as early as the first trimester. The researchers did not examine associations between C. innocuum and other medical conditions in these cohorts; their analysis focused on gut microbiome composition and preterm birth outcomes. The findings were published Thursday in the journal Cell Host & Microbe.

"Estradiol regulates critical pathways that sustain pregnancy and initiate the process of childbirth," said Zelei Miao of Westlake University, the paper's first author. Corresponding author An Pan of Huazhong University of Science and Technology said the results "may make it important to monitor the gut microbiome to prevent potential adverse pregnancy outcomes" for women who are pregnant or planning to become pregnant.

Investigators propose two, non‑mutually exclusive pathways by which C. innocuum could increase preterm birth risk. One is direct biochemical activity: the bacterium produces an enzyme that degrades estradiol, which could lower systemic levels of the hormone. Low estradiol in early pregnancy has been associated with higher risks of miscarriage and may undermine processes that maintain pregnancy. The second proposed pathway is immune activation. Pregnancy involves adaptive changes in the maternal immune system to tolerate the fetus, and the authors say C. innocuum may trigger immune responses that contribute to premature initiation of labor.

The study notes broader health implications tied to both estrogen and C. innocuum. Prior research has linked C. innocuum to chronic inflammation and a correlation with certain cancers; several studies have also reported a protective, anti-inflammatory role for estrogen in colon cancer development. The authors say disruption of estrogen metabolism by gut bacteria may therefore affect health beyond pregnancy and could relate to previously observed cancer associations.

Global health authorities estimate roughly one in 10 births worldwide is premature, contributing to about one million child deaths annually. Preterm birth is also linked to longer-term health risks. A prior study from the Icahn School of Medicine reported that women who deliver prematurely have higher risks of mortality from any cause in the subsequent decade and may face elevated risks of conditions such as heart disease and diabetes in later life.

The authors caution that their findings have limitations. The research drew on two China‑based cohorts with a relatively low prevalence of preterm birth, and the results may not generalize to other populations or ethnic groups. The population analysis is observational and can establish association but not definitive causation; while the enzyme experiments provide a plausible mechanism for estradiol degradation, further interventional and mechanistic studies are required to confirm causal pathways and to evaluate whether modifying the gut microbiome can reduce preterm birth risk.

The team said future work will seek to clarify how C. innocuum interacts with estrogen signaling and the immune system, and whether interventions—such as targeted microbiome monitoring or modulation—could prevent adverse pregnancy outcomes. Independent experts not involved in the study have said more research across diverse populations and controlled clinical studies will be necessary before clinical recommendations can be made.

The study adds to a growing body of research linking the maternal gut microbiome with pregnancy outcomes, and highlights a potential hormone‑microbiome interaction that warrants further investigation as researchers and clinicians seek new approaches to reduce the global burden of prematurity.