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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1-ZL-I)
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National Jewish Health
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Williams, Michael R; Nakatsuji, Teruaki; Sanford, James A et al. (2017) Staphylococcus aureus Induces Increased Serine Protease Activity in Keratinocytes. J Invest Dermatol 137:377-384
Nakatsuji, Teruaki; Chen, Tiffany H; Narala, Saisindhu et al. (2017) Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med 9:
Liu, Haiyun; Archer, Nathan K; Dillen, Carly A et al. (2017) Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses. Cell Host Microbe 22:653-666.e5
Oyoshi, Michiko K; Venturelli, Nicholas; Geha, Raif S (2016) Thymic stromal lymphopoietin and IL-33 promote skin inflammation and vaccinia virus replication in a mouse model of atopic dermatitis. J Allergy Clin Immunol 138:283-6
Shi, Baochen; Bangayan, Nathanael J; Curd, Emily et al. (2016) The skin microbiome is different in pediatric versus adult atopic dermatitis. J Allergy Clin Immunol 138:1233-1236
Leung, Donald Y M (2016) Clinical implications of new mechanistic insights into atopic dermatitis. Curr Opin Pediatr 28:456-62
Galand, Claire; Leyva-Castillo, Juan Manuel; Yoon, Juhan et al. (2016) IL-33 promotes food anaphylaxis in epicutaneously sensitized mice by targeting mast cells. J Allergy Clin Immunol 138:1356-1366
Malhotra, Nidhi; Yoon, Juhan; Leyva-Castillo, Juan Manuel et al. (2016) IL-22 derived from ?? T cells restricts Staphylococcus aureus infection of mechanically injured skin. J Allergy Clin Immunol 138:1098-1107.e3
Gallo, Richard L; Hultsch, Thomas; Farnaes, Lauge (2016) Recognizing that the microbiome is part of the human immune system will advance treatment of both cancer and infections. J Am Acad Dermatol 74:772-4
Li, Shan; Ganguli-Indra, Gitali; Indra, Arup K (2016) Lipidomic analysis of epidermal lipids: a tool to predict progression of inflammatory skin disease in humans. Expert Rev Proteomics 13:451-6

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