Development of a Human Skin Commensal Microbe for Bacteriotherapy of Atopic Dermatitis and Use in a Phase 1 Randomized Clinical Trial

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2021 Feb 23

PMID 33619370

Citations 98

Authors

Teruaki Nakatsuji

Tissa R Hata

Yun Tong

Joyce Y Cheng

Faiza Shafiq

Anna M Butcher

Secilia S Salem

Samantha L Brinton

Amanda K Rudman Spergel

Keli Johnson

Brett Jepson

Agustin Calatroni

Gloria David

Marco Ramirez-Gama

Patricia Taylor

Donald Y M Leung

Richard L Gallo

Affiliations

Soon will be listed here.

Abstract

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 (ShA9), a bacterium isolated from healthy human skin, as a topical therapy for AD. ShA9 killed S. aureus on the skin of mice and inhibited expression of a toxin from S. aureus (psmα) that promotes inflammation. A first-in-human, phase 1, double-blinded, randomized 1-week trial of topical ShA9 or vehicle on the forearm skin of 54 adults with S. aureus-positive AD (NCT03151148) met its primary endpoint of safety, and participants receiving ShA9 had fewer adverse events associated with AD. Eczema severity was not significantly different when evaluated in all participants treated with ShA9 but a significant decrease in S. aureus and increased ShA9 DNA were seen and met secondary endpoints. Some S. aureus strains on participants were not directly killed by ShA9, but expression of mRNA for psmα was inhibited in all strains. Improvement in local eczema severity was suggested by post-hoc analysis of participants with S. aureus directly killed by ShA9. These observations demonstrate the safety and potential benefits of bacteriotherapy for AD.

Citing Articles

Skin microbiome and dermatologic disorders.

Scharschmidt T, Segre J J Clin Invest. 2025; 135(3).

PMID: 39895627 PMC: 11785926. DOI: 10.1172/JCI184315.

Skin microbiota: pathogenic roles and implications in atopic dermatitis.

Huang C, Zhuo F, Guo Y, Wang S, Zhang K, Li X Front Cell Infect Microbiol. 2025; 14:1518811.

PMID: 39877655 PMC: 11772334. DOI: 10.3389/fcimb.2024.1518811.

Bidirectional Mendelian Randomization Analysis to Study the Relationship Between Human Skin Microbiota and Radiation-Induced Skin Toxicity.

Chen H, Xia X, Shi K, Xie T, Sun X, Xu Z Microorganisms. 2025; 13(1).

PMID: 39858962 PMC: 11767967. DOI: 10.3390/microorganisms13010194.

Advances in Microbiome-Based Therapeutics for Dermatological Disorders: Current Insights and Future Directions.

Madaan T, Doan K, Hartman A, Gherardini D, Ventrola A, Zhang Y Exp Dermatol. 2024; 33(12):e70019.

PMID: 39641544 PMC: 11663288. DOI: 10.1111/exd.70019.

Understanding the role of in atopic dermatitis: strain diversity, microevolution, and prophage influences.

Wang Z, Hulpusch C, Traidl-Hoffmann C, Reiger M, Schloter M Front Med (Lausanne). 2024; 11:1480257.

PMID: 39624034 PMC: 11608963. DOI: 10.3389/fmed.2024.1480257.

References

Kapoor R, Menon C, Hoffstad O, Bilker W, Leclerc P, Margolis D . The prevalence of atopic triad in children with physician-confirmed atopic dermatitis. J Am Acad Dermatol. 2007; 58(1):68-73. DOI: 10.1016/j.jaad.2007.06.041. View

Bieber T . Atopic dermatitis. N Engl J Med. 2008; 358(14):1483-94. DOI: 10.1056/NEJMra074081. View

Nutten S . Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab. 2015; 66 Suppl 1:8-16. DOI: 10.1159/000370220. View

Reed B, Blaiss M . The burden of atopic dermatitis. Allergy Asthma Proc. 2018; 39(6):406-410. DOI: 10.2500/aap.2018.39.4175. View

Bin L, Leung D . Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin Immunol. 2016; 12:52. PMC: 5069938. DOI: 10.1186/s13223-016-0158-5. View

Weidinger S, Beck L, Bieber T, Kabashima K, Irvine A . Atopic dermatitis. Nat Rev Dis Primers. 2018; 4(1):1. DOI: 10.1038/s41572-018-0001-z. View

Langan S, Irvine A, Weidinger S . Atopic dermatitis. Lancet. 2020; 396(10247):345-360. DOI: 10.1016/S0140-6736(20)31286-1. View

Nakatsuji T, Gallo R . The role of the skin microbiome in atopic dermatitis. Ann Allergy Asthma Immunol. 2018; 122(3):263-269. PMC: 7147826. DOI: 10.1016/j.anai.2018.12.003. View

Leyden J, MARPLES R, Kligman A . Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol. 1974; 90(5):525-30. DOI: 10.1111/j.1365-2133.1974.tb06447.x. View

10.

Kong H, Oh J, Deming C, Conlan S, Grice E, Beatson M . Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012; 22(5):850-9. PMC: 3337431. DOI: 10.1101/gr.131029.111. View

11.

Nakatsuji T, Chen T, Two A, Chun K, Narala S, Geha R . Staphylococcus aureus Exploits Epidermal Barrier Defects in Atopic Dermatitis to Trigger Cytokine Expression. J Invest Dermatol. 2016; 136(11):2192-2200. PMC: 5103312. DOI: 10.1016/j.jid.2016.05.127. View

12.

Leung D . Infection in atopic dermatitis. Curr Opin Pediatr. 2003; 15(4):399-404. DOI: 10.1097/00008480-200308000-00008. View

13.

Bekeredjian-Ding I, Inamura S, Giese T, Moll H, Endres S, Sing A . Staphylococcus aureus protein A triggers T cell-independent B cell proliferation by sensitizing B cells for TLR2 ligands. J Immunol. 2007; 178(5):2803-12. DOI: 10.4049/jimmunol.178.5.2803. View

14.

Vu A, Baba T, Chen X, Le T, Kinoshita H, Xie Y . Staphylococcus aureus membrane and diacylated lipopeptide induce thymic stromal lymphopoietin in keratinocytes through the Toll-like receptor 2-Toll-like receptor 6 pathway. J Allergy Clin Immunol. 2010; 126(5):985-93, 993.e1-3. DOI: 10.1016/j.jaci.2010.09.002. View

15.

Nakamura Y, Oscherwitz J, Cease K, Chan S, Munoz-Planillo R, Hasegawa M . Staphylococcus δ-toxin induces allergic skin disease by activating mast cells. Nature. 2013; 503(7476):397-401. PMC: 4090780. DOI: 10.1038/nature12655. View

16.

Howell M, Gallo R, Boguniewicz M, Jones J, Wong C, Streib J . Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity. 2006; 24(3):341-8. DOI: 10.1016/j.immuni.2006.02.006. View

17.

Mallbris L, Carlen L, Wei T, Heilborn J, Nilsson M, Granath F . Injury downregulates the expression of the human cathelicidin protein hCAP18/LL-37 in atopic dermatitis. Exp Dermatol. 2009; 19(5):442-9. DOI: 10.1111/j.1600-0625.2009.00918.x. View

18.

Ong P, Ohtake T, Brandt C, Strickland I, Boguniewicz M, Ganz T . Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med. 2002; 347(15):1151-60. DOI: 10.1056/NEJMoa021481. View

19.

Hata T, Kotol P, Boguniewicz M, Taylor P, Paik A, Jackson M . History of eczema herpeticum is associated with the inability to induce human β-defensin (HBD)-2, HBD-3 and cathelicidin in the skin of patients with atopic dermatitis. Br J Dermatol. 2010; 163(3):659-61. PMC: 2966528. DOI: 10.1111/j.1365-2133.2010.09892.x. View

20.

Howell M, Boguniewicz M, Pastore S, Novak N, Bieber T, Girolomoni G . Mechanism of HBD-3 deficiency in atopic dermatitis. Clin Immunol. 2006; 121(3):332-8. DOI: 10.1016/j.clim.2006.08.008. View