Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gut Microbes Pub Date : 2024-01-01 Epub Date: 2024-05-10 DOI:10.1080/19490976.2024.2351532
Qing-Yun Hao, Jing Yan, Jin-Tao Wei, Yu-Hong Zeng, Li-Yun Feng, Dong-Dong Que, Shi-Chao Li, Jing-Bin Guo, Ying Fan, Yun-Fa Ding, Xiu-Li Zhang, Ping-Zhen Yang, Jing-Wei Gao, Ze-Hua Li
{"title":"<i>Prevotella copri</i> promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.","authors":"Qing-Yun Hao, Jing Yan, Jin-Tao Wei, Yu-Hong Zeng, Li-Yun Feng, Dong-Dong Que, Shi-Chao Li, Jing-Bin Guo, Ying Fan, Yun-Fa Ding, Xiu-Li Zhang, Ping-Zhen Yang, Jing-Wei Gao, Ze-Hua Li","doi":"10.1080/19490976.2024.2351532","DOIUrl":null,"url":null,"abstract":"<p><p>Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of <i>Prevotella copri</i> (<i>P. copri</i>) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of <i>P. copri</i> and aortic calcification scores. Moreover, oral administration of live <i>P. copri</i> aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells <i>in vivo</i>, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. <i>In vitro</i> and <i>ex vivo</i> experiments consistently demonstrated that <i>P. copri</i>-derived LPS (<i>Pc</i>-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, <i>Pc</i>-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated <i>Pc</i>-LPS-induced VSMC calcification. Our study clarifies a novel role of <i>P. copri</i> in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including <i>Pc</i>-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight <i>P. copri</i> and its-derived LPS as potential therapeutic targets for VC in CKD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":null,"pages":null},"PeriodicalIF":12.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093026/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut Microbes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19490976.2024.2351532","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

前驱菌通过激活 NF-κB 信号通路,通过脂多糖促进血管钙化。
新的证据表明,肠道微生物群的改变在慢性肾脏病(CKD)相关血管钙化(VC)中扮演着重要角色。我们的目的是研究与 CKD-VC 相关的特定肠道微生物群及其潜在机制。通过 16S rRNA 基因的扩增子测序,我们发现在患有慢性肾脏病(CKD)并伴有主动脉钙化的大鼠(采用 5/6 肾切除术,然后以高钙和磷酸盐饮食诱发)粪便中,Prevotella copri(P. copri)的丰度有所增加。在慢性肾脏病患者中,我们进一步证实了 P. copri 的丰度与主动脉钙化评分之间存在正相关。此外,口服活的 P. copri 会加重 CKD 相关的 VC 和体内血管平滑肌细胞的成骨分化,同时伴有肠道破坏、Toll 样受体-4(TLR4)表达增强和脂多糖(LPS)水平升高。体外和体内实验一致证明,源自 P. copri 的 LPS(Pc-LPS)可加速高磷酸盐诱导的 VC 和 VSMC 成骨分化。从机理上讲,Pc-LPS 与 TLR4 结合,然后在 VC 过程中激活核因子κB(NF-κB)和核苷酸结合域、富含亮氨酸的家族、含吡啶域-3(NLRP3)炎性体信号。抑制 NF-κB 可减少 NLRP3 炎性体,减轻 Pc-LPS 诱导的血管内皮细胞钙化。我们的研究阐明了 P. copri 在 CKD 相关 VC 中的新作用,其机制包括增加炎症调节代谢物(包括 Pc-LPS)和激活 NF-κB/NLRP3 信号通路。这些发现突出表明,P. copri 及其衍生的 LPS 是 CKD VC 的潜在治疗靶点。
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
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信