Pathogenetic Gut Microbiota in Aortic Diseases: Evidence and Mechanisms Across Aneurysm, Dissection, and Inflammatory Aortopathies

TL;DR

This paper explores how gut microbiota may influence aortic diseases like aneurysms and dissections, focusing on mechanisms and evidence from observational and experimental studies.

Contribution

The paper provides a synthesis of current evidence linking gut microbiome alterations to aortic diseases, emphasizing translational implications and highlighting gaps in causal inference.

Findings

Gut dysbiosis and reduced microbial diversity are strongly associated with abdominal aortic aneurysms.

Microbiota-derived metabolites like trimethylamine-N-oxide and lipopolysaccharides interact with pathways involved in vascular inflammation and matrix degradation.

Evidence for thoracic aortic aneurysms and dissection is limited, suggesting microbiota may act as a modifier rather than a primary driver.

Abstract

Aortic diseases, including abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA), aortic dissection (AD), and Takayasu arteritis (TAK), are characterized by vascular remodeling and chronic immune–inflammatory activation, with AD often representing an acute complication of long-standing aortic wall vulnerability. Increasing evidence suggests that gut dysbiosis, impaired intestinal barrier integrity, and microbiota-derived metabolites may contribute to aortic wall injury. We synthesized current evidence linking the gut microbiome to aortic diseases and explored potential translational implications. PubMed, Scopus, and Web of Science were searched for microbiome-related studies on AAA, TAA, AD, and TAK published up to December 2025. Human observational and interventional studies were integrated with relevant experimental research. The strongest evidence was identified for AAA, where multiple cohorts report gut dysbiosis and reduced microbial diversity. Translational studies have detected bacterial DNA and microbial products in blood, aneurysm wall, or intraluminal thrombus, consistent with barrier-related microbial signaling and vascular inflammation, although these low-biomass findings do not establish microbial viability or causality. Microbiota-derived mediators—including trimethylamine-N-oxide, lipopolysaccharides, short-chain fatty acids, and bile acid derivatives—interact with pathways involved in cytokine signaling, oxidative stress, innate immune activation, and extracellular matrix degradation. Evidence for TAA and AD remains limited and suggests mainly modifier effects, whereas early studies in TAK indicate disease-associated microbiome and metabolite alterations. Mendelian randomization analyses have explored genetically proxied microbiome–AAA associations; however, results are heterogeneous, and causal inference remains provisional. Overall, the gut microbiome emerges as a plausible modifier of aortic disease, with the greatest translational relevance in AAA, highlighting the need for longitudinal multi-compartment studies and targeted interventions with aortic endpoints.

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