In a 763-participant cohort study using brachial-ankle pulse wave velocity measurement, ITS sequencing, and untargeted LC-MS metabolomics, five fungal genera — Apiotrichum, Mycothermus, Flavocillium, Hyaloscypha, and Microscypha — emerged as network-driving species correlated with elevated arterial stiffness. Individuals with higher stiffness showed a less clustered but more intercommunicative fungal community architecture. Organic acids, fatty acyls, and alkaloids partially mediated the fungi-stiffness relationship, while key molecular transducers included alpha-1A and alpha-2B adrenergic receptors, ACE, angiotensin II receptor type 1, MMP-2, TNF, CYP11B2, and ROCK2.
The gut bacteriome's role in cardiovascular aging is increasingly established, but the mycobiome — fungi — has been a neglected frontier. This study is among the first to systematically map fungal interaction networks against a direct hemodynamic measure of vascular aging, making it notable even as a cross-sectional, observational design. Causality cannot be inferred: whether fungal dysbiosis drives stiffness or vascular dysfunction reshapes the gut environment remains unresolved. The metabolite-mediation findings are compelling but require validation in interventional models. The adrenergic and renin-angiotensin pathway connections suggest potential mechanistic plausibility — these are well-established vasoregulatory axes. Practically, no actionable intervention emerges yet, but the work positions gut antifungal or probiotic strategies as a theoretically legitimate cardiovascular research target. Incremental but directionally important for the field.