The skin microbiome and fungal infections of indigenous Malaysians - Skin fungal infections are common, recurrent, and difficult to control, yet the microbial, environmental, and host determinants of persistence and transmission remain poorly defined. The Orang Asli of Peninsular Malaysia experience a high prevalence of tinea imbricata (>30% in some villages), a chronic dermatophyte infection caused by Trichophyton concentricum, a pathogen not reported in the United States. This endemic setting in Malaysia provides essential access to investigate sustained transmission, the emergence of antifungal resistance, and chronic T. concentricum infection under natural exposure conditions that cannot be studied in U.S. populations, where this pathogen is absent. This foreign study is therefore scientifically necessary to define host.fungal.microbiome interactions under conditions of ongoing natural exposure. These data cannot be replicated in U.S.- based cohorts or laboratory models. The results will inform U.S. public health by identifying biological mechanisms of chronic dermatophyte infection, strengthening preparedness for imported or emerging fungal pathogens, and advancing microbiome-based approaches to the prevention and treatment of skin disease. In a preliminary study of 361 participants across multiple villages, we quantified village-level prevalence and collected samples for fungal culture and metagenomic sequencing. Early data demonstrate a reduced abundance of the bacterium Cutibacterium acnes and an increased prevalence of previously uncharacterized microbial taxa in less industrialized settings, suggesting measurable microbiome differences associated with environmental exposures and infection status. Aim 1 will expand epidemiologic sampling across .6 villages stratified by quantifiable variables, including household income, water source, sanitation access, nutritional status, mobility, animal exposure, and distance to healthcare facilities. We will model associations between these variables and infection prevalence and severity. Aim 2 will perform shotgun metagenomic sequencing to identify microbial taxa and functional pathways associated with T. concentricum infection. Aim 3 will conduct whole-genome sequencing of .100 fungal isolates to identify genetic variation associated with antifungal resistance and chronic infection. Together, these aims will generate quantitative and reproducible datasets linking microbiome composition, environmental exposures, and fungal genomics to infection outcomes. The findings will identify candidate targets for improved diagnostics, prevention, and treatment of dermatophyte infections relevant to the United States, including infections caused by related species such as T. rubrum, and will strengthen U.S. capacity to respond to emerging fungal threats. This project leverages an established collaboration among Universiti Malaya and NIH investigators from NIAID, NHGRI, and NIAMS, supporting rigorous study design, standardized protocols, accountable data generation, transparent oversight, and direct integration of the findings into U.S.- based research and public health frameworks.
