<i>Apiotrichum</i> ‐Centered Fungal Interaction Network Disturbance Correlates With Increased Arterial Stiffness

The gut mycobiome plays an essential role in human health, yet its influence on the progression of arterial stiffness, a key feature of vascular aging, remains obscure. In this study, we aimed to investigate the involvement of intestinal fungi in the exacerbation of arterial stiffness. In total, 763 participants were invited for the brachial-ankle pulse wave velocity test to determine their status of arterial stiffness. The gut mycobiome was identified through internal transcribed spacer sequencing, host genetics were determined by genotyping arrays, and plasma metabolites were quantified using untargeted liquid chromatography-mass spectrometry. A less clustered but more communicative fungal community was found in individuals with elevated stiffness. Five driving fungal genera contributing to the shift of fungal interaction networks from normal to elevated stiffness, including Apiotrichum, Mycothermus, Flavocillium, Hyaloscypha, and Microscypha, were associated with arterial stiffness. Integrative analysis with metabolomics further demonstrated that organic acids, fatty acyls, and alkaloids mediated the effect of Apiotrichum, Mycothermus, and Microscypha on arterial stiffness. Moreover, alpha-1A adrenergic receptor, alpha-2B adrenergic receptor, cytochrome P450 Family 11 subfamily B member 2, angiotensin I converting enzyme, angiotensin II receptor type 1, matrix metallopeptidase 2, tumor necrosis factor, and rho-associated coiled-coil containing protein kinase 2 were identified as the key molecular transducers associated with increased Apiotrichum in arterial stiffness. Our study uncovers a strong association between disruption in gut fungi and the progression of elevated arterial stiffness, and highlights the potential of targeting the gut mycobiome for improving vascular health.