Multi-omics analyses reveal host-microbe interactions in atopic dermatitis and psoriasis

Atopic dermatitis (AD) and psoriasis (PSO) are chronic inflammatory skin diseases that impose substantial physical and psychological burdens. Although fungal-bacterial balance is important for skin immune homeostasis, the role of the skin mycobiome and its interaction with bacterial communities and host immunity in these diseases remains poorly understood.

To characterize alterations in the skin mycobiome and its interactions with bacterial communities and host immune responses in AD and PSO.

Adult patients with chronic AD, plaque-type PSO and healthy volunteers were included in this study. Skin microbiota samples and biopsies were collected from lesional and non-lesional skin areas, including the posterior thigh for AD and the lower back for PSO. Whole-metagenome shotgun sequencing was used to profile microbial communities. SparCC was used to construct fungal-bacterial co-occurrence networks, and integration of host transcriptomic and microbial features was performed using O2PLS.

Both AD and PSO showed disease-associated restructuring of Malassezia species and reduced fungal-bacterial ecological connectivity in lesional skin. In AD, Malassezia arunalokei was inversely associated with Staphylococcus aureus and linked to antimicrobial peptide-centred host gene modules enriched for IL-17 signalling. Its abundance decreased with increasing disease severity and inversely correlated with inflammatory immune cell signatures. In PSO, altered Malassezia composition was associated with IL-17-driven transcriptional programmes and lipid metabolic pathways, suggesting interactions between fungal imbalance and inflammatory-metabolic processes.

Our findings expand current models of skin dysbiosis beyond bacteria and suggest that disrupted fungal-bacterial interactions are linked to immune activation in AD and PSO and, in AD, to disease severity. Although further validation is required, skin microbiome features may provide clinically relevant information for disease monitoring, patient stratification and future microbiome-informed therapeutic strategies. Our study lays the groundwork for microbiome modulation as a potential therapeutic strategy for AD and PSO.