Journal Article

Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial

Hata, Tissa R., Shafiq, Faiza, David, Gloria, Ramirez-Gama, Marco, Tong, Yun, Cheng, Joyce Y., Salem, Secilia S., Calatroni, Agustin, Brinton, Samantha L., Butcher, Anna M., Jepson, Brett, Taylor, Patricia, Gallo, Richard L., Johnson, Keli, Nakatsuji, Teruaki, Rudman Spergel, Amanda K., Leung, Donald Y. M.

2021

نظرة عامة

Staphylococcus aureus colonizes patients with atopic dermatitis (AD) and exacerbates disease by promoting inflammation. The present study investigated the safety and mechanisms of action of Staphylococcus hominis A9 ( Sh A9), a bacterium isolated from healthy human skin, as a topical therapy for AD. Sh A9 killed S. aureus on the skin of mice and inhibited expression of a toxin from S. aureus ( psm α) that promotes inflammation. A first-in-human, phase 1, double-blinded, randomized 1-week trial of topical Sh A9 or vehicle on the forearm skin of 54 adults with S. aureus -positive AD (NCT03151148) met its primary endpoint of safety, and participants receiving Sh A9 had fewer adverse events associated with AD. Eczema severity was not significantly different when evaluated in all participants treated with Sh A9 but a significant decrease in S. aureus and increased Sh A9 DNA were seen and met secondary endpoints. Some S. aureus strains on participants were not directly killed by Sh A9, but expression of mRNA for psm α was inhibited in all strains. Improvement in local eczema severity was suggested by post-hoc analysis of participants with S. aureus directly killed by Sh A9. These observations demonstrate the safety and potential benefits of bacteriotherapy for AD. First-in-human test of topical application of a commensal bacterium on skin of individuals with atopic dermatitis reduces colonization by proinflammatory Staphylococcus aureus .

• الناشر: Nature Publishing Group US,Nature Publishing Group
• موضوع: 631/250 / 631/326 / 692/699/249/2510/1415 / Administration, Topical / Adolescent / Adult / Adverse events / Aged / Aged, 80 and over / Animals / Atopic dermatitis / Bacteria / Bacterial Proteins - metabolism / Bacteriocins - pharmacology / Bacteriology / Biological products / Biomedical and Life Sciences / Biomedicine / Cancer Research / Care and treatment / Colonization / Colony Count, Microbial / Cultures and culture media / Dermatitis / Dermatitis, Atopic - microbiology / Dermatitis, Atopic - therapy / Dermatologic agents / Dermatology / Eczema / Forearm / Formulae, receipts, prescriptions / Gene expression / Humans / Infectious Diseases / Inflammation / Inflammation - complications / Inflammation - pathology / Metabolic Diseases / Mice, Inbred BALB C / Microbial Sensitivity Tests / Microbial Viability - drug effects / Microorganisms / Middle Aged / Molecular Medicine / mRNA / Neurosciences / Penicillin / Peptides, Cyclic - metabolism / Reproducibility of Results / Safety / Skin / Skin - drug effects / Skin - microbiology / Skin - pathology / Skin diseases / Staphylococcal Infections - microbiology / Staphylococcal Infections - therapy / Staphylococcus aureus / Staphylococcus aureus - drug effects / Staphylococcus aureus - growth & development / Staphylococcus aureus - physiology / Staphylococcus aureus infections / Staphylococcus hominis - physiology / Testing / Topical application / Toxins / Transcription, Genetic - drug effects / Treatment Outcome / Virulence Factors - metabolism / Young Adult