Background The emerging role of fungal communities in human health and diseases has been well recognized in recent years, particularly for the mucosa-associated mycobiome which is fundamental in the regulation of host immune homeostasis and assembly of microbial communities. However, a comprehensive characterization of human mycobiome across multiple organs in simultaneous and their potential relations remains largely unexplored. The study aims to investigate the composition, diversity, spatial distribution, and interaction of human mycobiome across a diversity of body sites spanning multiple organs.

Methods We conducted an extensive sampling on 53 diverse anatomical sites of skin and organs along the entire gastrointestinal tract (oral cavity, esophagus, stomach, small intestine, appendix, and large intestine) from 33 deceased subjects. A total of 1610 samples were collected and subjected to fungal community profiling employing internal transcribed Spacer 2 (ITS2) sequencing. The influence of multiple factors such as habitats, individuality, age, and BMI on the variation of fungal communities across the human body was also assessed.

Results Here, we showed remarkable variation in diversity and structure of fungal communities which were mainly driven by the individuality and biogeographic habitats at both inter- and intra-organ levels. The mucosa of multiple GI organs was consistently inhabited by a set of core fungal taxa including Candida, Malassezia, Cladosporium, and Saccharomyces which represented drivers in 4 distinct fungal community types. We also revealed homogeneous/heterogeneous distribution of fungal communities across intra-organ sites and determined signature fungi and interactions specific for each site across different organs. The community heterogeneity between mucosa and their lumen counterparts within the stomach, small intestine, and large intestine has been revealed. Neutral community modeling further demonstrated a considerable contribution of lumen fungi in the assembly of mucosal mycobiome along the intestinal tract. Moreover, cross-kingdom network analyses revealed common/specific fungi-fungi and fungi-bacteria interactions across diverse regions along the entire GI tract.

Conclusions Our study provides a comprehensive landscape of human mycobiome across diverse organs and their relationships at unprecedented resolution, which will further enhance our understanding towards their implications in human health and diseases.