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

Gut Microbes. 2024 Jan-Dec;16(1):2351532. doi: 10.1080/19490976.2024.2351532. Epub 2024 May 10.


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.

Keywords: Vascular calcification; chronic kidney disease; gut microbiota; lipopolysaccharides; prevotella copri.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Feces / microbiology
  • Gastrointestinal Microbiome*
  • Humans
  • Inflammasomes / metabolism
  • Lipopolysaccharides* / metabolism
  • Male
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism
  • NF-kappa B* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Osteogenesis / drug effects
  • Prevotella* / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / microbiology
  • Renal Insufficiency, Chronic / pathology
  • Signal Transduction*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Vascular Calcification* / metabolism
  • Vascular Calcification* / microbiology
  • Vascular Calcification* / pathology


  • Inflammasomes
  • Lipopolysaccharides
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Toll-Like Receptor 4

Supplementary concepts

  • Prevotella copri

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (82200442, 82070247, 82370237 and 82000460) and the Guangdong Basic and Applied Basic Research Foundation (2022A1515012263).