Plasma trimethylamine N-oxide (TMAO), a gut microbiota–derived metabolite, may identify risk for abdominal aortic aneurysm (AAA). A prospective cohort study published in JAMA evaluated 237 individuals in Uppsala, Sweden, and 658 individuals in Cleveland, Ohio, who underwent serial aortic imaging and long-term outcome monitoring between October 2023 and May 2025.

Plasma TMAO concentrations, measured by liquid chromatography with tandem mass spectrometry, predicted AAA risk independent of cardiovascular risk factors and kidney function. In the European cohort, elevated TMAO increased the risk of fast-growing AAA (≥4.0 mm per year; adjusted odds ratio [aOR], 2.75; 95% CI, 1.20–6.79) and surgical intervention (aOR, 2.67; 95% CI, 1.24–6.09). In the US cohort, high TMAO levels more than doubled the risk of rapid growth (aOR, 2.71; 95% CI, 1.53–4.80) and surgical repair (aOR, 2.73; 95% CI, 1.56–4.80). Combined analysis confirmed elevated risk of both outcomes (fast-growing AAA: aOR, 2.30; 95% CI, 1.47–3.62; surgery: aOR, 2.41; 95% CI, 1.55–3.74).

The study demonstrates that TMAO strengthens risk stratification for AAA. Measuring TMAO levels can guide closer surveillance and support earlier surgical decision-making to reduce the risk of dissection or rupture.