Sex-related differences in gut dysbiosis influence vascular smooth muscle cell behavior in abdominal aortic aneurysm pathogenesis through microbial metabolites, sex hormones, and immune activation, but require further investigation to establish a clear relationship.
Gut microbial metabolites, specifically trimethylamine oxide (TMAO) and phenylacetyl glutamine (PAGln), have been linked to abdominal aortic aneurysm (AAA) pathogenesis via inflammation and vascular damage.
Sex hormones directly influence vascular smooth muscle cell (VSMC) phenotype switching in AAA pathogenesis.
Gut dysbiosis contributes to AAA progression through inflammation, vascular smooth muscle cell dysfunction, and immune activation.
Novel biomarkers and molecular regulators have emerged as potential therapeutic targets for AAA treatment.
The relationship between sex-related differences in gut dysbiosis and AAA pathogenesis requires further investigation to establish a clear mechanistic link.
This research reviews what is currently known about how differences in gut bacteria between men and women may contribute to the development of abdominal aortic aneurysms (AAAs) — dangerous bulges in the main artery of the abdomen that can rupture fatally. The review focuses on how the gut microbiome, the community of bacteria living in the digestive system, produces chemical byproducts that can travel through the bloodstream and affect the cells lining the walls of blood vessels. Two specific chemicals — TMAO and phenylacetyl glutamine — produced by gut bacteria appear to promote inflammation and damage blood vessel walls in ways that could lead to or worsen aneurysms. The review also highlights that sex hormones play an important role. Estrogen appears to protect blood vessel wall cells from the kind of harmful changes seen in AAAs, while testosterone may promote inflammation that drives aneurysm growth. These hormonal differences help explain why AAAs are far more common in men than in women. The interaction between an individual's gut bacteria, their sex hormones, and the behavior of specialized cells in the aortic wall (called vascular smooth muscle cells) appears to be a key part of how AAAs develop. This research suggests that the gut microbiome could be an important but underappreciated factor in AAA risk, and that treatments targeting gut bacteria or their metabolites could potentially offer new ways to prevent or slow aneurysm growth — particularly if tailored differently for men and women. However, the authors emphasize that the connections between these factors are still being established and that more research is needed before these insights can be translated into clinical practice.
Hatcher G, Kazaleh M, Patil R, Ailawadi G, Salmon M. (2026). Gut Dysbiosis, Sex, and Vascular Smooth Muscle Cells in Abdominal Aortic Aneurysms.. Current atherosclerosis reports. https://doi.org/10.1007/s11883-026-01461-9