{"title":"前驱菌通过激活 NF-κB 信号通路,通过脂多糖促进血管钙化。","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":"{\"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}","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}
Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.
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.
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.