Skip to main content

ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1411328

Gut Microbe-derived Metabolites and Risk of Cardiovascular Disease in the METSIM Cohort

Provisionally accepted
Sahereh Mirzaei Sahereh Mirzaei 1Holli A. Devon Holli A. Devon 1Rita M. Cantor Rita M. Cantor 1Arjen Cupido Arjen Cupido 2Markku Laakso Markku Laakso 3aldons j. Lusis aldons j. Lusis 1*
  • 1 University of California, Los Angeles, Los Angeles, United States
  • 2 University of Amsterdam, Amsterdam, Netherlands
  • 3 University of Eastern Finland, Kuopio, Northern Savonia, Finland

The final, formatted version of the article will be published soon.

    Background: An association between gut microbes and cardiovascular disease (CVD) has been established but underlying mechanisms remain largely unknown. Methods: We conducted a secondary analysis of cross-sectional data from the METSIM (Metabolic Syndrome In Men) population-based cohort of 10,194 Finish men (age=57.65 ± 7.12 years). We tested the levels of circulating gut-microbe derived metabolites as predictors of CVD, ischemic cerebrovascular accident (CVA), and myocardial infarction (MI). The Kaplan-Meier method was used to estimate the time from the participants first outpatient clinic visit to the occurrence of adverse outcomes. The associations of metabolite levels with the outcomes were assessed with Cox proportional hazard models. Results: During a median follow up of 200 months, 979, 397, and 548 participants experienced CVD, CVA, and MI respectively. After adjustment for traditional risk factors and correction for multiple comparisons, higher plasma levels of succinate (quartile 4 vs. quartile 1; adjusted hazard ratio (aHR=1.30, [CI, 1.10-1.53] p=0.0003. adj. p=0.01) were significantly associated with risk for CVD. High plasma levels of ursodeoxycholic acid (quartile 3 vs. quartile 1); (aHR=1.68, [CI, 1.26-2.2]; p=0.0003, adj. p=0.01) were associated with higher risk of CVA. As a continuous variable, succinate was associated with a 10% decreased risk for CVD (aHR= 0.9; [CI, 0.84-0.97]; P = 0.008) and 15% decreased in risk of MI, (aHR=0.85, [CI, 0.77-0.93]; p=0.0007) respectively. Conclusion: Gut microbe-derived metabolites, succinate and ursodeoxycholic acid were associated with CVD, MI, and CVA. Modulating the gut microbes may represent a potential therapeutic target for modulating CVD and CVA.

    Keywords: gut metabolites, succinate, Ursodeoxycholic Acid, cardiovascular disease, Myocardial Infarction, Stroke

    Received: 02 Apr 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Mirzaei, Devon, Cantor, Cupido, Laakso and Lusis. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: aldons j. Lusis, University of California, Los Angeles, Los Angeles, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.