Molecular and clinical interactions between gut microbiota and endothelial dysfunction: A review of mechanisms and therapeutic perspectives
Steliana Simona Tudor 1 * , Claudia Simona Stefan 1 , Caterina Nela Dumitru 1 , Ancuta Iacob 1 , Ionela Daniela Fertu 1
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1 Faculty of Medicine and Pharmacy, Research Center in the Medical-Pharmaceutical Field, “Dunărea de Jos” University of Galați, Galați, ROMANIA* Corresponding Author

Abstract

Cardiovascular diseases remain the leading cause of mortality worldwide, accounting for approximately 32% of all deaths recorded in 2022, according to data provided by the World Health Organization. Although traditional risk factors are well known, a significant proportion of residual cardiovascular risk remains unexplained. Over the last decade, the gut microbiota has gained interest as an essential regulator of metabolic and immune homeostasis, and the concept of “gut-heart axis” has gained increasing attention in medical literature. This review aims to synthesize the current evidence we have linking gut dysbiosis to endothelial dysfunction in various vascular pathologies. It will analyze the molecular mechanisms through which microbiota-derived metabolites such as trimethylamine-N-oxide (TMAO), short-chain fatty acids, and bacterial lipopolysaccharides modulate nitric oxide bioavailability, vascular inflammation, and oxidative stress. Furthermore, the paper discusses the clinical implications of these interactions and the potential of therapeutic strategies based on microbiome modulation through probiotics, prebiotics, or fecal transplant in restoring proper endothelial function. Understanding the complexity of this axis and the gut-heart interactions offers valuable insights for personalized medicine and cardiovascular prevention. This review brings novelty by integrating recent molecular and clinical evidence on the gut-heart axis, highlighting microbiota-derived metabolites as potential therapeutic targets.

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article Type: Review Article

ELECTRON J GEN MED, Volume 23, Issue 4, August 2026, Article No: em743

https://doi.org/10.29333/ejgm/18972

Publication date: 15 Jul 2026

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