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REVIEW article

Front. Endocrinol.
Sec. Gut Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1409119
This article is part of the Research Topic The Mechanism in Gut Microbiota of Diabetes and Endocrine Complications: Preventive and Therapeutic Target View all 9 articles

Gut Microbiota-Derived Imidazole Propionate: An Emerging Target for the Prevention and Treatment of Cardiometabolic Diseases

Provisionally accepted
Yan Zeng Yan Zeng 1Qi Wu Qi Wu 1Man Guo Man Guo 2Fang-Yuan Teng Fang-Yuan Teng 2Chunxia Jiang Chunxia Jiang 1Jiao Chen Jiao Chen 2Xiaozhen Tan Xiaozhen Tan 2Chen Zeng Chen Zeng 2Yang Long Yang Long 2Yuen Kwan Law Yuen Kwan Law 1Yong Xu Yong Xu 1*
  • 1 Macau University of Science and Technology, Taipa, Macao, SAR China
  • 2 The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China

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

    Despite significant advancements in prevention and treatment, cardiometabolic diseases continue to pose a high burden of incidence and mortality. The chronic progression of these diseases necessitates the identification of early and complementary therapeutic targets to elucidate and mitigate residual risks in patient care. The gut microbiota acts as a sentinel between internal and external environments, transmitting modified risks associated with these factors to the host. Imidazole propionate (ImP), a histidine metabolite originating from the gut microbiota, gained attention after being found to impair glucose tolerance and insulin signaling several years ago.Epidemiological studies over the past five years have demonstrated a robust correlation between ImP and an increased risk of onset of type 2 diabetes (T2D) and obesity, exacerbation of kidney traits in chronic kidney disease (CKD), progression of atherosclerotic plaques, and elevated mortality rates in heart failure (HF). These findings suggest that ImP may serve as a pivotal target for the prevention and treatment of cardiometabolic diseases. Mechanistic insights have uncovered associations between ImP and insulin resistance, impaired glucose metabolism, chronic inflammation, and intestinal barrier damage. This review provides a comprehensive summary of the current evidence regarding the association between ImP and cardiometabolic impairment, highlighting its potential in advancing personalized approaches to disease prevention and management, and exploring the intricate interplay of diet, gut microbiota, and ImP in cardiovascular metabolic impairment. Overall, this review 4 offers valuable insights into the multifaceted roles of ImP in cardiometabolic diseases, identifies current knowledge gaps, and discusses future research directions.

    Keywords: AMPK, adenosine 5′-monophosphate-activated protein kinase, BMI, body mass index, CAD, coronary artery disease, CDAHFD, choline-deficient amino acid-defined high-fat diet, CKD, chronic kidney disease, CVD, cardiovascular disease, eGFR, estimated glomerular filtration rate, HF, heart failure

    Received: 29 Mar 2024; Accepted: 23 Jan 2025.

    Copyright: © 2025 Zeng, Wu, Guo, Teng, Jiang, Chen, Tan, Zeng, Long, Law and Xu. 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: Yong Xu, Macau University of Science and Technology, Taipa, Macao, SAR China

    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.