Dietary Inflammation, Gut Mycobiota, and Microbial Cross-Kingdom Associations with Cardiovascular Health in Older Adults

Background/Objectives: Dietary inflammation may influence cardiometabolic health, yet the gut mycobiome and bacterial–fungal interactions remain unclear. Building upon our earlier findings and data from the TALENTs trial (Targeting Aging and Longevity with Exogenous Nucleotides) baseline data, we explored gut fungal profiles and bacterial–fungal co-occurrence patterns in relation to the Dietary Inflammatory Index (DII) and Life’s Essential 8 (LE8) in older adults. Methods: We enrolled 301 community residents aged 60–70 years, with 285 providing qualified fungal internal transcribed spacer (ITS) sequencing data. DII scores were derived from 3-day dietary records to reflect dietary inflammatory risk, and LE8 (integrating health behaviors including physical activity and metabolic health factors including BMI, blood lipids, blood pressure, and blood glucose) was used to assess cardiovascular health; LE8_non-diet was applied as a sensitivity measure. Fungal diversity, genus-level taxa, ecological guilds, and bacterial–fungal associations were analyzed using diversity indices, ZINB/Hurdle models, bootstrap, E-values, DIABLO analysis, and network construction. Results: DII showed an inverse correlation with LE8_non-diet (r = −0.130, p = 0.024). Fungal alpha and beta diversity did not differ significantly across DII-defined groups. Conversely, better cardiovascular status was linked to higher fungal richness, with significantly elevated Chao1 and ACE indices in the high-CVH group (both p < 0.05). Additionally, integrated ZINB, Hurdle, and stability analyses jointly pinpointed four candidate fungal genera that correlated with both DII and LE8. Both ZINB and DIABLO analyses consistently indicated that antagonistic interactions dominated gut bacterial–fungal associations (89.9% vs. 63.8% of negative associations, respectively), with DIABLO further revealing synchronized community-level co-variation between the two kingdoms (r = 0.325, p < 0.01). FUNGuild prediction further revealed saprotrophic guilds enriched in the high-CVH group and host-associated guilds in the low-CVH group, with similar patterns across DII-defined groups. Conclusions: This cross-sectional study reveals gut mycobiome profiles and potential bacterial–fungal co-occurrence patterns among older adults stratified by dietary inflammatory potential and cardiovascular health status, generating testable hypotheses for subsequent nutritional and metabolic research integrating lifestyle behaviors and functional health outcomes.