Transplantation of human skin microbiota in models of atopic dermatitis
Ian A. Myles, Kelli W. Williams, Jensen D. Reckhow, Momodou L. Jammeh, Nathan B. Pincus, Inka Sastalla, Danial Saleem, Kelly D. Stone, Sandip K. Datta
Ian A. Myles, Kelli W. Williams, Jensen D. Reckhow, Momodou L. Jammeh, Nathan B. Pincus, Inka Sastalla, Danial Saleem, Kelly D. Stone, Sandip K. Datta
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Research Article Dermatology Immunology

Transplantation of human skin microbiota in models of atopic dermatitis

Abstract

Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to Staphylococcus aureus. Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes and can be medically modulated. S. aureus contributes to AD pathogenesis and can be mitigated by antibiotics and bleach baths. Recent work has revealed that the skin microbiome differs significantly between healthy controls and patients with AD, including decreased Gram-negative bacteria in AD. However, little is known about the potential therapeutic benefit of microbiome modulation. To evaluate whether parameters of AD pathogenesis are altered after exposure to different culturable Gram-negative bacteria (CGN) collected from human skin, CGN were collected from healthy controls and patients with AD. Then, effects on cellular and culture-based models of immune, epithelial, and bacterial function were evaluated. Representative strains were evaluated in the MC903 mouse model of AD. We found that CGN taken from healthy volunteers but not from patients with AD were associated with enhanced barrier function, innate immunity activation, and control of S. aureus. Treatment with CGN from healthy controls improved outcomes in a mouse model of AD. These findings suggest that a live-biotherapeutic approach may hold promise for treatment of patients with AD.

Authors

Ian A. Myles, Kelli W. Williams, Jensen D. Reckhow, Momodou L. Jammeh, Nathan B. Pincus, Inka Sastalla, Danial Saleem, Kelly D. Stone, Sandip K. Datta

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Figure 3

CGN from HV improves outcomes in the MC903 mouse model of AD-like dermatitis.

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CGN from HV improves outcomes in the MC903 mouse model of AD-like dermat...
(A and B) Both ears of mice were inoculated daily with R. mucosa from a HV or an AD patient or P. aeruginosa from a HV or SAAS9 strain of S. aureus for 2 days prior to MC903 application. Then, bacteria were coapplied with MC903 daily for 13 days. Day 14 ear thickness (A) for each ear and serum total IgE levels (B) are shown; n = 4–8 mice per group. (C and D) Mice were treated with MC903 for 14 days to induce AD-like dermatitis. Starting on day 13, mice were treated daily for 3 days with 1 × 106 CFU of live R. mucosa from a HV or AD patient (HVCGN and ADCGN), 1 × 106 CFU of killed R. mucosa from the same HV resuspended in the supernatant from 3 × 106 CFU of autologous R. mucosa (Dead mix), or supernatant from 1 × 107 CFU of the HV R. mucosa. Day 21 ear thickness (C) and visual redness (D) are shown; n = 3–5 mice per group. Significance versus the diluent group is shown unless otherwise indicated. Data shown are representative of 3 independent experiments and displayed as mean + SEM. HV, healthy volunteer; AD, atopic dermatitis; CGN, culturable Gram-negative; Rm, R. mucosa; Pa, P. aeruginosa. Significance determined by ANOVA with Bonferroni’s correction. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.