Mapping the human gut mycobiome in middle-aged and elderly adults: multiomics insights and implications for host metabolic health

Objective The human gut fungal community, known as the mycobiome, plays a fundamental role in the gut ecosystem and health. Here we aimed to investigate the determinants and long-term stability of gut mycobiome among middle-aged and elderly adults. We further explored the interplay between gut fungi and bacteria on metabolic health. Design The present study included 1244 participants from the Guangzhou Nutrition and Health Study. We characterised the long-term stability and determinants of the human gut mycobiome, especially long-term habitual dietary consumption. The comprehensive multiomics analyses were performed to investigate the ecological links between gut bacteria, fungi and faecal metabolome. Finally, we examined whether the interaction between gut bacteria and fungi could modulate the metabolic risk. Results The gut fungal composition was temporally stable and mainly determined by age, long-term habitual diet and host physiological states. Specifically, compared with middle-aged individuals, Blastobotrys and Agaricomycetes spp were depleted, while Malassezia was enriched in the elderly. Dairy consumption was positively associated with Saccharomyces but inversely associated with Candida. Notably, Saccharomycetales spp interacted with gut bacterial diversity to influence insulin resistance. Bidirectional mediation analyses indicated that bacterial function or faecal histidine might causally mediate an impact of Pichia on blood cholesterol. Conclusion We depict the sociodemographic and dietary determinants of human gut mycobiome in middle-aged and elderly individuals, and further reveal that the gut mycobiome may be closely associated with the host metabolic health through regulating gut bacterial functions and metabolites.

Automated summary

This study investigated the determinants and long-term stability of the gut mycobiome in middle-aged and elderly individuals. It also explored the ecological links between gut fungi, bacteria, and faecal metabolome, as well as the potential influence of gut fungi on metabolic health through interactions with gut bacterial functions and metabolites. The results showed that the composition of the gut mycobiome was temporally stable and mainly influenced by age, long-term habitual diet, and host physiological states. Dairy consumption was found to be associated with certain gut fungi, while other gut fungi were associated with insulin resistance and blood cholesterol levels through interactions with gut bacterial diversity and faecal histidine.