Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis - PubMed (original) (raw)

Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis

Heidi H Kong et al. Genome Res. 2012 May.

Abstract

Atopic dermatitis (AD) has long been associated with Staphylococcus aureus skin colonization or infection and is typically managed with regimens that include antimicrobial therapies. However, the role of microbial communities in the pathogenesis of AD is incompletely characterized. To assess the relationship between skin microbiota and disease progression, 16S ribosomal RNA bacterial gene sequencing was performed on DNA obtained directly from serial skin sampling of children with AD. The composition of bacterial communities was analyzed during AD disease states to identify characteristics associated with AD flares and improvement post-treatment. We found that microbial community structures at sites of disease predilection were dramatically different in AD patients compared with controls. Microbial diversity during AD flares was dependent on the presence or absence of recent AD treatments, with even intermittent treatment linked to greater bacterial diversity than no recent treatment. Treatment-associated changes in skin bacterial diversity suggest that AD treatments diversify skin bacteria preceding improvements in disease activity. In AD, the proportion of Staphylococcus sequences, particularly S. aureus, was greater during disease flares than at baseline or post-treatment, and correlated with worsened disease severity. Representation of the skin commensal S. epidermidis also significantly increased during flares. Increases in Streptococcus, Propionibacterium, and Corynebacterium species were observed following therapy. These findings reveal linkages between microbial communities and inflammatory diseases such as AD, and demonstrate that as compared with culture-based studies, higher resolution examination of microbiota associated with human disease provides novel insights into global shifts of bacteria relevant to disease progression and treatment.

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Figures

Figure 1.

Figure 1.

AD disease severity. (A) Representative clinical images of the antecubital (Ac, left) and popliteal creases (Pc, right) in two patients with overall disease severity scores (objective SCORAD). (B) Longitudinal objective SCORAD trend for each patient (n = 12) at baseline, flare, and postflare.

Figure 2.

Figure 2.

Microbial community-level statistics in the AD microbiome. (A) Relationship between objective SCORAD and Shannon diversity in the Ac of AD patients. Partial correlation (adjusting for disease state). (B) Longitudinal Shannon diversity trend in AD grouped by no-treatment (trt) and intermittent-trt flares (n = 12, Ac). (C) Mean Shannon diversity ± SEM in controls and all AD disease states (Ac, Pc, volar forearm [Vf], nares [_N_]). (D) Mean theta (θ) similarity coefficients ± SEM. Pairwise comparisons of community structure between individuals within a control or AD disease group. Bars represent average of all pairwise comparisons of community structure for control individuals to other controls, baselines to baselines, flares(no-trt)-flares(no-trt), flare(intermittent-trt)-flare(intermittent-trt), and postflares-postflares.

Figure 3.

Figure 3.

Bacterial taxonomic classifications in the AD skin microbiome. (A) Mean relative abundance of the 14 major phyla-order in the antecubital (Ac) and popliteal creases (Pc) for controls and AD disease states: baseline, flare (no-treatment [trt] and intermittent-trt), and postflare (Supplemental Table S13 for order of subjects). (B) Mean relative abundances for Ac and Pc of species-level classifications of staphylococcal species. Order of subjects follows A.

Figure 4.

Figure 4.

Relationship between staphylococcal species and AD. (A) Longitudinal trend of mean proportion of S. aureus in AD in antecubital and popliteal creases (AcPc, n = 12) grouped by no-treatment (trt) and intermittent-trt flares. (B) Proportion of S. aureus and Shannon diversity index in AcPc. Partial correlation (adjusting for disease state, AcPc). (C) Longitudinal trend of mean proportion of S. epidermidis in AcPc. (D) Correlation of proportion of S. aureus versus objective SCORAD for each site (Ac, Pc, Volar forearm/Vf, Nares/N). Partial correlation (adjusting for disease state and site).

Figure 5.

Figure 5.

Shannon diversity index during flares. Circles indicate AD patients with a full longitudinal cycle (baseline, flare, and postflare). Triangles indicate flares from four additional (add'l) patients. Means between no-treatment (trt) and intermittent-trt tested with Wilcoxon rank-sum test (P < 0.0025, n = 16).

Figure 6.

Figure 6.

AD microbiome progression hypothesis. (*) Proposed relationship among shifts in skin microbial diversity, the proportion of Staphylococcus, and disease severity.

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