Abstract
BackgroundThe skin harbors complex communities of resident microorganisms, yet little is known of their physiological roles and the molecular mechanisms that mediate cutaneous host-microbe interactions. Here, we profiled skin transcriptomes of mice reared in the presence and absence of microbiota to elucidate the range of pathways and functions modulated in the skin by the microbiota.ResultsA total of 2820 genes were differentially regulated in response to microbial colonization and were enriched in gene ontology (GO) terms related to the host-immune response and epidermal differentiation. Innate immune response genes and genes involved in cytokine activity were generally upregulated in response to microbiota and included genes encoding toll-like receptors, antimicrobial peptides, the complement cascade, and genes involved in IL-1 family cytokine signaling and homing of T cells. Our results also reveal a role for the microbiota in modulating epidermal differentiation and development, with differential expression of genes in the epidermal differentiation complex (EDC). Genes with correlated co-expression patterns were enriched in binding sites for the transcription factors Klf4, AP-1, and SP-1, all implicated as regulators of epidermal differentiation. Finally, we identified transcriptional signatures of microbial regulation common to both the skin and the gastrointestinal tract.ConclusionsWith this foundational approach, we establish a critical resource for understanding the genome-wide implications of microbially mediated gene expression in the skin and emphasize prospective ways in which the microbiome contributes to skin health and disease.
Highlights
The skin harbors complex communities of resident microorganisms, yet little is known of their physiological roles and the molecular mechanisms that mediate cutaneous host-microbe interactions
Commensal microbiota modulate the cutaneous transcriptome To measure the genome-wide impact of microbial colonization on cutaneous gene transcription, we sequenced and compared the mRNA transcriptome of skin from mice raised in the absence of microbiota to conventionally raised mice (Fig. 1a)
Isolated from murine germ free (GF; n = 9) and specific pathogen free, conventionally raised (SPF; n = 7) skin was sequenced on the Illumina HiSeq 2000 to obtain over 1.2 billion paired-end reads of good quality (Additional file 2: Figure S1A)
Summary
The skin harbors complex communities of resident microorganisms, yet little is known of their physiological roles and the molecular mechanisms that mediate cutaneous host-microbe interactions. As a barrier to the external environment, the skin harbors microbial communities that are both topographically diverse and temporally complex [1,2,3,4]. These microbes are postulated to have important functions in skin health [2], including colonization resistance to block invasion of pathogenic bacteria and regulation of the cutaneous inflammatory and immune response [5,6,7]. The full extent of cutaneous functions regulated by the skin microbiota remains unknown and previous work has focused heavily on characterizing the response of specific pathways to microbial colonization. Recent work in mouse models demonstrates that the commensal microbiota, along with hair follicle morphogenesis, is responsible for recruitment of regulatory T cells during neonatal life [15]
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