Recent work has concluded that some commensal bacteria residing on human skin are beneficial to immune defense. In contrast, colonization by S. aureus of the skin of patients with atopic dermatitis is detrimental. Through high-throughput screening of the normal human skin microbiome we have identified specific strains of commensal coagulase-negative Staphylococcus that kill pathogenic bacteria and enhance skin innate immune defense. Analysis of the function of the skin microbiome from atopic dermatitis patients has further shown that most atopic patients are deficient in these beneficial commensal strains. We therefore hypothesize that increasing the abundance of such commensal bacteria will benefit patients with atopic dermatitis. To test these hypothesis we propose an interventional clinical trial of the topical application of a defined combination of 4 bacteria from the human skin microbiome. We will confirm that this ?transplant? of beneficial bacteria will kill S. aureus on patient skin. We then determine the stability of this transplant in order to design appropriate dosing over a 28-day trial period and evaluate several elements of the host immune response. This intervention will test if transplant of the skin microbiome will benefit subjects with atopic dermatitis by decreasing S. aureus colonization and/or improve inflammation. Therefore, successful completion of this project will provide answers to key questions about the function of the microbiome on human skin and provide a new approach to treat atopic dermatitis.
Our specific aims are: 1: Evaluate the capacity of a microbiome transplant to decrease S. aureus colonization in patients with atopic dermatitis (AD). 2: Determine the stability of the microbiome transplant on lesional and matched non-lesional skin of AD subjects and normal subjects. 3: Evaluate the clinical response to microbiome transplant and identify relevant biomarkers associated with the clinical response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI117673-04
Application #
9455592
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
076443019
City
Denver
State
CO
Country
United States
Zip Code
80206
Simpson, Eric L; Villarreal, Miguel; Jepson, Brett et al. (2018) Patients with Atopic Dermatitis Colonized with Staphylococcus aureus Have a Distinct Phenotype and Endotype. J Invest Dermatol 138:2224-2233
O'Neill, Alan M; Gallo, Richard L (2018) Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris. Microbiome 6:177
Berdyshev, Evgeny; Goleva, Elena; Bronova, Irina et al. (2018) Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight 3:
Shi, Baochen; Leung, Donald Y M; Taylor, Patricia A et al. (2018) Methicillin-Resistant Staphylococcus aureus Colonization Is Associated with Decreased Skin Commensal Bacteria in Atopic Dermatitis. J Invest Dermatol 138:1668-1671
Li, Jin; Zheng, Le; Uchiyama, Akihiko et al. (2018) A data mining paradigm for identifying key factors in biological processes using gene expression data. Sci Rep 8:9083
Malhotra, Nidhi; Leyva-Castillo, Juan Manuel; Jadhav, Unmesh et al. (2018) ROR?-expressing T regulatory cells restrain allergic skin inflammation. Sci Immunol 3:
Bin, Lianghua; Li, Xiaozhao; Richers, Brittany et al. (2018) Ankyrin repeat domain 1 regulates innate immune responses against herpes simplex virus 1: A potential role in eczema herpeticum. J Allergy Clin Immunol 141:2085-2093.e1
Dyjack, Nathan; Goleva, Elena; Rios, Cydney et al. (2018) Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2-high atopic dermatitis disease endotype. J Allergy Clin Immunol 141:1298-1309
Archer, Nathan K; Jo, Jay-Hyun; Lee, Steven K et al. (2018) Injury, dysbiosis, and filaggrin deficiency drive skin inflammation through keratinocyte IL-1? release. J Allergy Clin Immunol :
Leyva-Castillo, Juan Manuel; Yoon, Juhan; Geha, Raif S (2018) IL-22 promotes allergic airway inflammation in epicutaneously sensitized mice. J Allergy Clin Immunol :

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