Abstract
Labor induction failure increases the risk of unplanned cesarean delivery and maternal-neonatal complications. However, the determinants of induction sensitivity remain poorly understood. In this prospective cohort of 85 term pregnant women undergoing labor induction with Propess® (prostaglandin E2), we combined full-length 16S rRNA sequencing of the vaginal microbiota, untargeted metabolomics of vaginal secretions, and transcriptomic analysis of cervical stromal cells exposed to Lactobacillus crispatus supernatant to identify predictive factors and underlying mechanisms. We found that women with a poor induction response exhibited higher vaginal microbiota α-diversity and a significant reduction in L. crispatus abundance. The relative abundance of L. crispatus predicted induction success with an area under the curve (AUC) of 0.80 (95% CI: 0.70–0.90). Metabolomic analysis revealed distinct vaginal metabolic alterations in induction-insensitive women. Importantly, in vitro experiments showed that L. crispatus supernatant directly modulates the transcriptome of cervical stromal cells, upregulating genes involved in uterine contraction, tissue remodeling, and immune regulation. Our results identify vaginal L. crispatus as a key biomarker for labor induction sensitivity and elucidate a potential mechanism by which it primes the cervix for prostaglandin response. These findings provide a novel microbiota–host interaction framework for personalizing induction strategies in precision obstetrics.
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Data availability
The 16S rRNA gene amplicon and RNA-seq data generated in this study have been deposited in the Genome Sequence Archive (GSA) for Human under accession numbers HRA014736 and HRA0148066, respectively. The raw LC-MS metabolomics data are available in the OMIX database under accession number OMIX014446. All data are currently accessible for peer review via the following private links: GSA: https://ngdc.cncb.ac.cn/gsa-human/s/94b7Gjmy and https://ngdc.cncb.ac.cn/gsa-human/s/YWzeu1sn. OMIX: https://ngdc.cncb.ac.cn/omix/preview/raSF9jRW All data will be made publicly available upon acceptance of the manuscript.
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Acknowledgements
We would like to express our gratitude to all participants who provided samples and clinical information for this study, and we also acknowledge the financial support funded by the National Key Research and Development Program of China (2022YFC2704402) and the National Natural Science Foundation of China (82403347).
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Zizhuo Wang designed the study, analyzed the data, wrote and revised the manuscript. Weidong Tan collected the samples and clinical data. Zhenzhen He, Liangnan Zhang, Yilin Fu, Nary Long, Phannaroat Sourn, Weikun Li, Junjie Yuan, Yuxin Chen, and Huihui Yu prepared the material and collected the samples. Wanjiang Zeng, Ling Feng, Jianli Wu, Shaoshuai Wang, and Wencheng Ding communicated with the patients and organized the cohort. Jianli Wu, Shaoshuai Wang, and Wencheng Ding supervised this project and revised the manuscript. All authors have read the final manuscript and approved it for publication.
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Wang, Z., Tan, W., He, Z. et al. A microbiota–host axis mediates prostaglandin sensitivity: Lactobacillus crispatus as a biomarker and regulator of human labor induction. npj Biofilms Microbiomes (2026). https://doi.org/10.1038/s41522-026-00960-6
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DOI: https://doi.org/10.1038/s41522-026-00960-6
