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

Nat Med. 2021 Apr;27(4):700-709. doi: 10.1038/s41591-021-01256-2. Epub 2021 Feb 22.


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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Topical
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Bacterial Proteins / metabolism
  • Bacteriocins / pharmacology
  • Colony Count, Microbial
  • Dermatitis, Atopic / microbiology*
  • Dermatitis, Atopic / therapy*
  • Humans
  • Inflammation / complications
  • Inflammation / pathology
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Middle Aged
  • Peptides, Cyclic / metabolism
  • Reproducibility of Results
  • Skin / drug effects
  • Skin / microbiology*
  • Skin / pathology
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / therapy
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / physiology
  • Staphylococcus hominis / physiology*
  • Transcription, Genetic / drug effects
  • Treatment Outcome
  • Virulence Factors / metabolism
  • Young Adult


  • AgrD protein, Staphylococcus
  • Bacterial Proteins
  • Bacteriocins
  • Peptides, Cyclic
  • Virulence Factors

Associated data