Department of Neurology, Zhongshan Hospital and Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Yan Yan
CAS Key Laboratory of Molecular Virology and Immunology, Chinese Academy of Sciences (CAS)
Yanni Pu
State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University
Shuchun Lin
The Academy of Medical Science, Zhengzhou University
Jian-Ge Qiu
The Academy of Medical Science, Zhengzhou University
Bing-Hua Jiang
The Academy of Medical Science, Zhengzhou University
Marisa Isabell Keller
European Molecular Biology Laboratory, Structural and Computational Biology Unit
Mingyu Wang
Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular Imaging, Center for Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology
Peer Bork
European Molecular Biology Laboratory, Structural and Computational Biology Unit
Wei-Hua Chen
Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular Imaging, Center for Artificial Intelligence Biology, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology
Yan Zheng
State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University
Xing-Ming Zhao
Department of Neurology, Zhongshan Hospital and Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Abstract Background The fungal component of the human gut microbiome, also known as the mycobiome, plays a vital role in intestinal ecology and human health. However, the overall structure of the gut mycobiome as well as the inter-individual variations in fungal composition remains largely unknown. In this study, we collected a total of 3363 fungal sequencing samples from 16 cohorts across three continents, including 572 newly profiled samples from China. Results We identify and characterize four mycobiome enterotypes using ITS profiling of 3363 samples from 16 cohorts. These enterotypes exhibit stability across populations and geographical locations and significant correlation with bacterial enterotypes. Particularly, we notice that fungal enterotypes have a strong age preference, where the enterotype dominated by Candida (i.e., Can_type enterotype) is enriched in the elderly population and confers an increased risk of multiple diseases associated with a compromised intestinal barrier. In addition, bidirectional mediation analysis reveals that the fungi-contributed aerobic respiration pathway associated with the Can_type enterotype might mediate the association between the compromised intestinal barrier and aging. Conclusions We show that the human gut mycobiome has stable compositional patterns across individuals and significantly correlates with multiple host factors, such as diseases and host age. Video Abstract