Clostridium difficile-derived membrane vesicles promote fetal growth restriction via inhibiting trophoblast motility through PPARγ/RXRα/ANGPTL4 axis.

IF 7.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

npj Biofilms and Microbiomes Pub Date : 2024-12-31 DOI:10.1038/s41522-024-00630-5

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

{"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.

查看原文本刊更多论文

艰难梭菌衍生膜囊通过PPARγ/RXRα/ANGPTL4轴抑制滋养细胞运动促进胎儿生长受限。

胎儿生长受限（FGR）是妊娠期常见的并发症，严重危害胎儿健康，目前仍缺乏有效的治疗靶点。艰难梭菌（C. difficile）与胎儿出生体重有关，其膜囊泡（MVs）是致病载体。然而，艰难梭菌及其mv在FGR中的作用尚不清楚。在这里，我们发现补充艰难梭菌改变了肠道微生物群的特征，并降低了小鼠的出生体重。有趣的是，艰难梭菌mv进入胎盘，抑制滋养细胞运动，诱导小鼠胎儿体重减轻。在机制上，艰难梭菌mv通过增强PPARγ启动子的转录活性来激活PPAR途径，从而抑制滋养细胞的运动。PPARγ在FGR胎盘中的表达显著升高，且与胎儿出生体重呈负相关。总之，我们的研究结果揭示了艰难梭菌及其mv在FGR中的重要性，为FGR的发展机制提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

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.