Clostridium difficile-derived membrane vesicles promote fetal growth restriction via inhibiting trophoblast motility through PPARγ/RXRα/ANGPTL4 axis
Fetal growth restriction (FGR) is a common complication of pregnancy, which seriously endangers fetal health and still lacks effective therapeutic targets. Clostridium difficile (C. difficile) is associated with fetal birth weight, and its membrane vesicles (MVs) are pathogenic vectors. However, the role of C. difficile and its MVs in FGR remains unclear. Here we found that supplementation with C. difficile altered the characteristics of gut microbiota and reduced the birth weight in mice. Interestingly, C. difficile MVs entered placenta, inhibited trophoblast motility, and induced fetal weight loss in mice. Mechanistically, C. difficile MVs activated the PPAR pathway via enhancing the transcriptional activity of PPARγ promoter, consequently inhibiting trophoblast motility. Moreover, PPARγ expression was significantly elevated in FGR placenta, and negatively correlated with fetal birth weight. Together, our findings reveal the significance of C. difficile and its MVs in FGR, providing new insights into the mechanisms of FGR development.
Authors
- Zhiqiang Zha (ORCID: https://orcid.org/0000-0003-3292-0947)
- Linyu Peng (ORCID: https://orcid.org/0000-0003-2021-0737)
- Menglan Pang
- Yiguo Hu (ORCID: https://orcid.org/0000-0002-3973-2140)
- Chunhong Jia (ORCID: https://orcid.org/0000-0001-6677-6061)
- Qudong Yin (ORCID: https://orcid.org/0000-0002-7347-1773)
- Ruisi Zhou
- Xiaowei Qiu
- Liping Huang (ORCID: https://orcid.org/0000-0002-1463-2768)
- Shijing Lu
- Yichi Zhang (ORCID: https://orcid.org/0000-0001-8948-466X)
- Yu Wang (ORCID: https://orcid.org/0000-0002-8683-6196)
- Ying Chen (ORCID: https://orcid.org/0000-0003-0582-380X)
- Yucheng Zhong (ORCID: https://orcid.org/0000-0001-6081-3327)
- Zhipeng Huang (ORCID: https://orcid.org/0000-0002-8414-6570)
- Chao Sheng (ORCID: https://orcid.org/0000-0003-2823-854X)
Institutions
- Third Affiliated Hospital of Guangzhou Medical University (CN)
- Nanfang Hospital (CN)
- Southern Medical University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- npj Biofilms and Microbiomes
- Published
- 2024-12-31
- DOI
- https://doi.org/10.1038/s41522-024-00630-5
- Citations
- 2
- Primary Topic
- Adolescent and Pediatric Healthcare
- Type
- article
- Field-Weighted Citation Impact
- 1.75
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Guangdong Province
- Southern Medical University
- Nanfang Hospital