Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare


Whole metagenome analysis has the potential to reveal functional triggers of skin diseases, but issues of cost, robustness and sampling efficacy have limited its application. Here, we have established an alternative, clinically practical and robust metagenomic analysis protocol and applied it to 80 skin microbiome samples epidemiologically stratified for atopic dermatitis (AD). We have identified distinct non-flare, baseline skin microbiome signatures enriched for Streptococcus and Gemella but depleted for Dermacoccus in AD-prone versus normal healthy skin. Bacterial challenge assays using keratinocytes and monocyte-derived dendritic cells established distinct IL-1-mediated, innate and Th1-mediated adaptive immune responses with Staphylococcus aureus and Staphylococcus epidermidis. Bacterial differences were complemented by perturbations in the eukaryotic community and functional shifts in the microbiome-wide gene repertoire, which could exacerbate a dry and alkaline phenotype primed for pathogen growth and inflammation in AD-susceptible skin. These findings provide insights into how the skin microbial community, skin surface microenvironment and immune system cross-modulate each other, escalating the destructive feedback cycle between them that leads to AD flare.

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Figure 1: Baseline bacterial diversity and signatures associated with AD.
Figure 2: Hierarchical clustering comparing cytokine secretion profiles of human keratinocytes and dendritic cells with various bacterial supernatants.
Figure 3: Eukaryotic and viral diversity in AD-associated skin microbiomes.
Figure 4: Changes in Malassezia species composition associated with AD.
Figure 5: Functional and metabolic shifts in the AD skin microbiome.


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The authors thank all volunteers for donating their skin microbiome samples, the Biological Resource Centre at A*STAR for assistance with animal work, the Flow Cytometry Facility at the Singapore Immunology Network, A*STAR, for assistance with cell sorting, and G. Low, H. Chan and M. Unnaamalai for assistance with the isolation of epidermal LCs. This work was funded by an SRG National Healthcare Group grant to J.C., N.N. and M.B.Y.T. and A*STAR SPF funding for basic and translational skin research.

Author information




K.R.C., M.B.Y.T., F.T.C., J.E.A.C. and N.N. planned the study. A.S.L.T., A.H.Q.N., J.W., N.M., B.J., X.F.C.C.W. and B.V.A. designed and conducted all experiments under the guidance of J.E.A.C., K.R.C., P.F.D.S., F.G. and J.E.C. Metagenomic data analysis was performed by K.R.C. and C.L. with supervision from N.N. Human skin tissue samples were collected by T.C.L. and A.W. provided technical computational assistance. B.K.S., S.A.M., Y.Y.S., F.T.C. and J.E.A.C. organized volunteer recruitment and sampling. K.R.C., A.S.L.T., E.B.L., J.E.A.C. and N.N. wrote the manuscript, with input from all authors.

Corresponding authors

Correspondence to John E. A. Common or Niranjan Nagarajan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information

Supplementary Notes 1–3, Supplementary References, Supplementary Figures 1–14, Supplementary Tables 1–3 and 8–10, Supplementary Tables 4–7 legends. (PDF 1224 kb)

Supplementary Table 4

Detailed metadata of study subjects. (XLSX 16 kb)

Supplementary Table 5

Table showing the relative abundances of different microbial genera and species in the skin microbiome of study subjects. (XLSX 99 kb)

Supplementary Table 6

Table showing pairwise Spearman correlations between the relative abundances of different skin microbial species across study subjects. (XLSX 17 kb)

Supplementary Table 7

Table showing SNPs of key staphylococcal virulence factors between cases and controls. (XLSX 14 kb)

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Chng, K., Tay, A., Li, C. et al. Whole metagenome profiling reveals skin microbiome-dependent susceptibility to atopic dermatitis flare. Nat Microbiol 1, 16106 (2016). https://doi.org/10.1038/nmicrobiol.2016.106

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