Transplantation of human skin microbiota in models of atopic dermatitis

Abstract

Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to Staphylococcus aureus. Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes and can be medically modulated. S. aureus contributes to AD pathogenesis and can be mitigated by antibiotics and bleach baths. Recent work has revealed that the skin microbiome differs significantly between healthy controls and patients with AD, including decreased Gram-negative bacteria in AD. However, little is known about the potential therapeutic benefit of microbiome modulation. To evaluate whether parameters of AD pathogenesis are altered after exposure to different culturable Gram-negative bacteria (CGN) collected from human skin, CGN were collected from healthy controls and patients with AD. Then, effects on cellular and culture-based models of immune, epithelial, and bacterial function were evaluated. Representative strains were evaluated in the MC903 mouse model of AD. We found that CGN taken from healthy volunteers but not from patients with AD were associated with enhanced barrier function, innate immunity activation, and control of S. aureus. Treatment with CGN from healthy controls improved outcomes in a mouse model of AD. These findings suggest that a live-biotherapeutic approach may hold promise for treatment of patients with AD.

First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis

“…AD severity was assessed using the SCORAD scale (20). Consistent with prior findings (16,17), enrollment cultures of the patients' antecubital fossae did not yield Gram-negative bacteria.…”

“…Notably, these reports never assessed whether the isolates of R. mucosa associated with clinical symptoms could fulfill Koch's postulates for defining pathogens. Our previous work found that R. mucosa application to mouse skin that had undergone tape-stripping or chemical-induced dermatitis provided clinical benefit for the mice without any signs of toxicity (17). However, prior to clinical use we assessed the potential for systemic spread of R. mucosa to cause pathology by injecting mice intravenously with 10 3 , 10 4 , or 10 8 colony-forming units (CFU) of 3 HV-derived R. mucosa strains independently, a strain of R. mucosa (ATCC BAA-692) isolated from a clinical blood culture (19), or saline diluent alone.…”

“…commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD (17). In contrast, application of an AD-sourced R. mucosa had either no impact on these modeled outcomes, or made the outcomes worse.…”

Микробиота Кожи И Возможности Ее Коррекции Пре- И Пробиотиками При Лечении Хронических Дерматозов

“…Трансплантация фекального микробиома была успешной при кишечных заболеваниях, таких как рецидивирующий псевдомембраноз-ный энтероколит и болезнь Крона, но данные относительно АД отсутствуют [7,109,110].…”

“…Для восстановления кожно-го микробиома при AД можно использовать трансплантацию микробиоты от здоровых до-бровольцев. В мышиной модели AД культиви-руемые грамотрицательные бактерии, такие как Roseomonas mucosa от здоровых добро-вольцев, уменьшали рост S. аureus, улучша-ли барьерную функцию кожи и активирова-ли врожденную иммунную функцию [7,115]. В дальнейшем такая обработка может стать доступной для больных людей.…”