{"title":"Clostridium difficile-derived membrane vesicles promote fetal growth restriction via inhibiting trophoblast motility through PPARγ/RXRα/ANGPTL4 axis.","authors":"Zhiqiang Zha, Chunhong Jia, Ruisi Zhou, Qinlan Yin, Yu Hu, Zhipeng Huang, Linyu Peng, Yichi Zhang, Xiaowei Qiu, Ying Chen, Yawen Zhong, Yu Wang, Menglan Pang, Shijing Lu, Chao Sheng, Liping Huang","doi":"10.1038/s41522-024-00630-5","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19370,"journal":{"name":"npj Biofilms and Microbiomes","volume":"10 1","pages":"158"},"PeriodicalIF":7.8000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688498/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Biofilms and Microbiomes","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41522-024-00630-5","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.