Cardiometabolic-Disease-Associated Gut Mycobiome Alterations and Their Relationship to Mediterranean Diet Adherence

Background: Gut fungal dysbiosis has been implicated in cardiometabolic disease (CMD), yet its relationship with dietary patterns remains poorly understood. We characterized associations among gut fungal composition, CMD risk factors, and Mediterranean diet adherence. Methods: In this cross-sectional analysis of an established population-based cohort (Alberta’s Tomorrow Project, Calgary, AB), adults aged 35–69 with diagnosed CMD and age-matched healthy controls (HC) were recruited. Anthropometric measures, blood biochemistry, clinical status, and the fecal mycobiome (ITS2) were assessed. Dietary intake was recorded using the validated Canadian Dietary History Questionnaire (CDHQ-II), and participants were stratified by low or high Mediterranean diet adherence (MedDietScore). Results: The gut mycobiome was highly individualized and significantly associated with alcohol intake and the dietary ratio of unsaturated to saturated fatty acids, suggesting lipid intake as a key driver of fungal community structure. Higher MedDietScore was associated with greater fungal diversity, particularly among participants with CMD. Independent of CMD status, high adherence corresponded to more favorable resting heart rate, hemoglobin A1c, and C-reactive protein. Within the CMD group, low adherence was linked to enrichment of Malasseziaceae/Malassezia, a lipophilic genus with proinflammatory potential, and to higher Ascomycota and lower Cladosporium basiinflatum relative to healthy controls (FDR p < 0.25); these signals were absent among participants with high adherence. Conclusions: MedDietScore adherence was associated with higher fungal diversity, attenuated CMD-related shifts in the gut mycobiome, and a more favorable cardiometabolic profile, supporting the link between diet-modulated mycobiome composition and cardiometabolic health. These findings add to growing evidence that the gut mycobiome is implicated in CMD risk.