%0 Journal Article %A Menglei Shuai %A Yuanqing Fu %A Hai-li Zhong %A Wanglong Gou %A Zengliang Jiang %A Yuhui Liang %A Zelei Miao %A Jin-Jian Xu %A Tien Huynh %A Mark L Wahlqvist %A Yu-ming Chen %A Ju-Sheng Zheng %T Mapping the human gut mycobiome in middle-aged and elderly adults: multiomics insights and implications for host metabolic health %D 2022 %R 10.1136/gutjnl-2021-326298 %J Gut %P gutjnl-2021-326298 %X 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.Data are available in a public, open access repository. The raw data of the ITS2 sequencing, 16S rRNA sequencing and metagenomic sequencing are available in the CNSA (https://db.cngb.org/cnsa/) of CNGBdb (accession number CNP0002114, CNP0000829 and CNP0001510, respectively). Other data sets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request. %U https://gut.bmj.com/content/gutjnl/early/2022/01/10/gutjnl-2021-326298.full.pdf