Uncovering the functional role of the skin mycobiome in atopic dermatitis

The National Institute of Allergy and Infectious Diseases awarded Dartmouth-Hitchcock Clinic $443,825 on August 11, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate the functional role of the skin mycobiome in atopic dermatitis, particularly head and neck disease subtype.

The research addresses a critical gap in understanding how fungal communities contribute to atopic dermatitis pathogenesis. While bacterial microbiome dysbiosis in atopic dermatitis has been extensively studied, the functional mechanisms of skin fungi remain poorly characterized. Head and neck atopic dermatitis affects over one-third of adult atopic dermatitis patients and shows resistance to emerging biologic therapies such as dupilumab. The project hypothesizes that altered atopic skin conditions select for functionally distinct fungal communities that reshape microbial interactions and host responses, thereby driving disease progression.

The research plan includes two primary aims. Aim 1 will define the composition and functional heterogeneity of head-and-neck-atopic-dermatitis-associated fungi using integrated metagenomics, culture-based genomics, and high-throughput phenotyping. Aim 2 will establish co-culture platforms to test how atopic skin conditions rewire fungal-fungal and fungal-bacterial interactions, characterized through metabolomics and transcriptomic analysis.

Performance occurs in Lebanon, New Hampshire. The period of performance runs from the award date through July 31, 2031. This is a project grant, the standard assistance type under the Allergy and Infectious Diseases Research program.

Abstract

Atopic dermatitis (ad) is the most common chronic inflammatory skin disease, affecting over 16 million adults in the united states. IT manifests as intensely itchy, painful, dry skin that is highly disruptive to daily life and increases risk for secondary infection. Despite the availability of new therapies, ad onset, severity, and response to treatment remain unpredictable. The head and neck subtype of ad (HND), which afflicts over one third of adult ad patients, is particularly burdensome. IT is often recalcitrant to emerging biologic therapies such as dupilumab and disproportionately impacts mental wellbeing. As such, new or supplemental therapies are desperately needed. A defining feature of ad and HND is microbiome dysbiosis, but while bacteria have been studied extensively, the functional role of the skin mycobiome (fungal communities) remains poorly understood. HND specifically is thought to be linked to the mycobiome. HND patients are often hypersensitized to fungal antigens and oral antifungals can provide temporary symptom relief. Therefore, HND is the ideal model to investigate the mechanistic contributions of the mycobiome to atopic skin disease and explore mycobiome derived therapies. In pursuit of this goal, this project launches a new research direction focused on the functional ecology of the skin mycobiome in HND. I hypothesize that the altered atopic skin environment selects for a functionally distinct fungal community that reshapes microbial interactions and host responses, thereby driving disease pathogenesis. Aim 1 will define the composition and functional heterogeneity of HND-associated fungi using integrated metagenomics, culture-based genomics, and high-throughput phenotyping. Aim 2 will establish innovative CO-culture platforms to test how atopic skin conditions rewire fungal-fungal and fungal-bacterial interactions, characterized by metabolomics, transcriptomics, and microscopy. Aim 3 will integrate fungal genetics, human skin biopsies, and primary keratinocytes to reveal how disease-altered environments transform fungal physiology and host-fungal interactions. This project is highly innovative in applying an ecological and functional lens to the mycobiome, moving beyond taxonomy to understand mechanisms that drive disease and treatment outcomes. By generating tools and models to manipulate and study skin-resident fungi, this work has the potential to redefine how the mycobiome is targeted therapeutically, shifting from indiscriminate eradication toward precise modulation of microbial activity and antigenicity. The results will provide a transformative framework for understanding and managing HND, an ad subtype that remains underserved by current treatments, with broad implications for other inflammatory skin diseases and microbiome-based interventions.