Longitudinal Study of the Psoriasis-Associated Skin Microbiome during Therapy with Ustekinumab in a Randomized Phase 3b Clinical Trial

J Invest Dermatol. 2018 Sep;138(9):1973-1981. doi: 10.1016/j.jid.2018.03.1501. Epub 2018 Mar 17.

Abstract

Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a phase 3b clinical trial. By sequencing the bacterial 16S ribosomal RNA gene from skin swab samples obtained at six anatomical sites, we identified minor, site-specific differences in microbial diversity and composition between pretreatment lesional and nonlesional skin. During therapy, microbial communities within lesional and nonlesional skin diverged, and body-site dispersion increased, reflecting microbial skin site-specificity. Microbiota demonstrated greater pretreatment heterogeneity in psoriatic lesions than in nonlesional skin, and variance increased as treatment progressed. Microbiota colonizing recurrent lesions did not overlap with pretreatment lesional microbiota, suggesting colonization patterns varied between initial and recurrent psoriatic lesions. While plaque psoriasis does not appear to be associated with specific microbes and/or microbial diversity, this large dataset provides insight into microbial variation associated with (i) disease in different body locations, (ii) initial versus recurrent lesions, and (iii) anti-IL12/23 therapy.

Trial registration: ClinicalTrials.gov NCT01550744.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Bacteria / genetics*
  • Bacteria / isolation & purification
  • Cross-Sectional Studies
  • Dermatologic Agents / administration & dosage
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Microbiota / drug effects*
  • Middle Aged
  • Psoriasis / drug therapy*
  • Psoriasis / metabolism
  • Psoriasis / microbiology
  • RNA, Bacterial / analysis
  • Retrospective Studies
  • Skin / microbiology*
  • Skin / pathology
  • Ustekinumab / administration & dosage*
  • Young Adult

Substances

  • Dermatologic Agents
  • RNA, Bacterial
  • Ustekinumab

Associated data

  • ClinicalTrials.gov/NCT01550744