Gut mycobiome alterations and network interactions with the bacteriome in patients with atherosclerotic cardiovascular disease

The connection between the gut mycobiome and atherosclerotic cardiovascular disease (ACVD) is largely uncharted. In our study, we compared the gut fungal communities of 214 ACVD patients with those of 171 healthy controls using shotgun metagenomic sequencing and examined their interactions with gut bacterial communities and network key taxa. The gut mycobiome composition in ACVD patients is significantly different, showing a rise in opportunistic pathogens like <i>Candida albicans</i>, <i>Exophiala spinifera</i>, and <i>Malassezia restricta</i>, with <i>Exophiala</i> and <i>Malassezia</i> showing the most significant changes (Wilcoxon rank-sum test, <i>P</i> < 0.001, fold change >10). Network analysis revealed a less interconnected and more uneven gut microbial network in ACVD patients. Network key taxa identified in the ACVD gut microbiome network include <i>Malassezia globosa</i> c182, <i>Nakaseomyces glabratus</i> c88, <i>Malassezia arunalokei</i> c192, and <i>Penicillium sumatraense</i> c22. Predictive models that integrated both bacterial and fungal taxa enhanced prediction accuracy, underscoring the critical role of gut fungi in ACVD. Our findings offer a thorough understanding of the link between the gut mycobiome and ACVD progression, which is vital for directing future therapeutic research.IMPORTANCEACVD is a leading cause of death and morbidity worldwide. While the role of the gut microbiome in ACVD development is recognized, the contribution of the gut mycobiome remains largely unexplored. Our study reveals significant alterations in the gut mycobiome of ACVD patients and identifies key fungal taxa associated with the disease. These findings underscore the importance of the gut mycobiome in the pathogenesis of ACVD and offer new avenues for developing preventive and therapeutic strategies targeting the gut fungal community. Our results provide valuable insights into the complex interplay between gut fungi and bacteria in ACVD, paving the way for novel therapeutic approaches.