Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

Atherosclerosis

The gut metabolite imidazole propionate is a potential biomarker of and therapeutic target for atherosclerosis

Nature Reviews Cardiology volume 22, page 701 (2025)Cite this article

Subjects

A growing body of evidence points to the importance of chronic inflammation and the gut microbiome as drivers of atherosclerosis. A new study published in Nature reports that oral administration of the microbial metabolite imidazole propionate (ImP) can induce atherosclerosis in atheroprone mice through the activation of the I1 imidazoline receptor (I1R) in myeloid cells, whereas blockade of I1R completely prevents ImP-induced atherosclerosis. These findings support the potential role of targeting the ImP–I1R axis in patients with atherosclerosis and further advance the field of microbiome-informed precision medicine for cardiovascular disease (CVD).

The investigators first screened for microbial metabolites involved in the progression of atherosclerosis in atheroprone Apoe–/– mice fed with different diets with or without antibiotic treatment. The gut microbiota-derived metabolite ImP was identified to be associated with atherosclerotic progression in mice fed a high-cholesterol diet. The plasma levels of ImP were also found to be elevated in two separate cohorts of individuals with subclinical atherosclerosis compared with their respective controls, which highlights the link between ImP and early atherosclerosis. Plasma ImP levels also directly correlated with numerous cardiovascular risk factors, including fasting glucose levels, body mass index and blood pressure. After adjusting for traditional cardiovascular risk factors, elevated ImP levels were found to be independently linked with atherosclerotic outcomes. Moreover, plasma ImP levels were further increased in patients with active atherosclerosis (as indicated by increased 18F-fluorodeoxyglucose (18F-FDG) uptake in arteries) as compared with those without arterial 18F-FDG uptake, and ImP improved risk stratification when added to conventional cardiovascular biomarkers, such as plasma LDL-cholesterol and C-reactive protein levels. Therefore, the investigators propose that ImP might be a useful marker of early active atherosclerosis, before the detection of other risk factors.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

Original article

Related article

  • Khuu, M. P. et al. The gut microbiota in thrombosis. Nat. Rev. Cardio. 22, 121–137 (2025)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nature Reviews Cardiology http://www.nature.com/nrcardio/

    Karina Huynh

Authors
  1. Karina Huynh
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Karina Huynh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huynh, K. The gut metabolite imidazole propionate is a potential biomarker of and therapeutic target for atherosclerosis. Nat Rev Cardiol 22, 701 (2025). https://doi.org/10.1038/s41569-025-01200-8

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41569-025-01200-8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research