Host transcriptomes that define microbiota during cutaneous homeostasis and inflammation

Recent findings demonstrate that human life is multiorganismal and microbe-host interactions play an important role in homeostasis and disease. While some insights have been generated in the gut, our understanding of microbe-host interactions in the skin is still limited. We have integrated metagenomic information from cutaneous microbes with transcriptome from healthy, non-lesional and lesional atopic and psoriatic skin (n=272) to elucidate key pathways influencing microbial composition as well as the host’s transcriptome. Here, we describe pathogen-driven and transcriptome-driven diversity loss in atopic dermatitis and psoriasis, respectively. Patterns significantly associated with these changes include the expression of antimicrobial peptides, loss and compensation of barrier-related genes, metal ion sequestration, alongside the occurrence of self-DNA in skin lesions as a potential microbe-interacting element. Among these, seven functionally heterogeneous gene clusters correlate with distinct microbial communities. Furthermore, correlated shifts in the microbiome were based not only on severity, but k-means clustering of subjects based on well-established disease markers. The key patterns of association add up to form diverse niches that either succeed or fail in limiting skin pathogen expansion. Our findings help to elucidate compensatory mechanisms that may account for fundamental differences in microbial composition.