Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

Amr Ali Mohamed Abdelgawwad El-Sehrawy; Usamah Sayed; Zarina Nasirova; Quvonch Tursunov; Omer Qutaiba B Allela; Lara Asim Kzar; Rajashree Panigrahi; Neeraj Bainsal

doi:10.1002/clc.70455

PubMed · 42655876

Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

Amr Ali Mohamed Abdelgawwad El-Sehrawy·Usamah Sayed·Zarina Nasirova·Quvonch Tursunov·Omer Qutaiba B Allela·Lara Asim Kzar·Rajashree Panigrahi·Neeraj Bainsal

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BACKGROUND: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. METHODS: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. RESULTS: Microbial metabolites-including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)-modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor-mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota-CVD associations. CONCLUSION: The gut-vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome-directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

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Amr Ali Mohamed Abdelgawwad El-Sehrawy, Usamah Sayed, Zarina Nasirova, Quvonch Tursunov, Omer Qutaiba B Allela, Lara Asim Kzar, Rajashree Panigrahi, Neeraj Bainsal. 2026. Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.. https://doi.org/10.1002/clc.70455

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Journal Article; Review resource Animals subject Cardiovascular disease subject Disease Models, Animal subject Dysbiosis subject Gastrointestinal Microbiome subject Humans subject Journal Article subject Observational Studies as Topic subject disease progression subject gut microbiome subject

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Long-term microbiome and clinical effects of a microbiome-guided personalized diet versus low-FODMAP diet in irritable bowel syndrome: A 12-month follow-up randomized controlled trial.

Metagenome-scale modeling to assess microbiome metabolic complementarity for precision microbiota transplantation therapies.

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