From prebiotics to engineered microbes: microbe-inspired treatments for atopic dermatitis

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with diverse clinical and histological features. While primarily immune-mediated, genetic studies have also highlighted the role of epithelium-expressed gene abnormalities (e.g. FLG mutations) as a key factor. Approaches to treating AD are multifaceted, involving barrier restoration, local anti-inflammatory treatment and, if needed, systemic immunosuppressive therapy. Genetic variations in the stratum corneum and the immune system are linked to an imbalance between the host and its microbiota, known as dysbiosis. An impaired skin barrier and immune responses can alter the microbial composition, while the skin microbiota itself can influence skin immunity and barrier formation. A hallmark of AD is increased bacterial colonization with Staphylococcus aureus, which is found on lesional skin in > 90% of patients with AD. It contributes to disease severity by driving further breakdown of the skin barrier and immune stimulation. The most common treatments for S. aureus infections in AD are topical or systemic antibiotics. While these treatments are typically reserved for active infections, they are sometimes prescribed to patients with AD without a clear skin infection. These treatments can disrupt commensal skin and gut microbiota, which play a critical role in maintaining skin and gut health. In this review we describe various treatments that target the skin microbiome to reduce infection and inflammation in AD, including transplantation of microbiota, and the use of prebiotics, probiotics and postbiotics. In addition, we provide a perspective to engineer and harness bacteria of the skin microbiome as next-generation probiotics, also known as engineered live biotherapeutic products, using synthetic biology to create strains that can sense skin signals, such as immune signals, and environmental factors, and produce therapeutic treatments for AD on demand.