{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:57:11Z","timestamp":1790582231273,"version":"4.1.0"},"reference-count":105,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Microbial metabolites\u2014including trimethylamine N\u2010oxide (TMAO), short\u2010chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)\u2014modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor\u2010mediated 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\u2010CVD associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The gut\u2010vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome\u2010directed 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clc.70455","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:11:01Z","timestamp":1787807461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5481-5617","authenticated-orcid":false,"given":"Amr Ali Mohamed Abdelgawwad","family":"El\u2010Sehrawy","sequence":"first","affiliation":[{"name":"Internal Medicine, Diabetes, Endocrinology and Metabolism Mansoura University Mansoura 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