426 Clinical improvement in atopic dermatitis following autologous application of microbiome therapy targeting Staphylococcus aureus

Select strains of coagulase-negative Staphylococcus (CoNS) produce antimicrobial peptides (AMPs) that kill Staphylococcus aureus (SA). These CoNS-AMP+ strains are common on normal skin but rare on patients with atopic dermatitis (AD) that are colonized by SA. We have previously shown that a single topical application of CoNS-AMP+ kills SA on AD subjects. Here, we hypothesized that extended treatment with CoNS-AMP+ would be well tolerated and could both suppress SA survival and improve local inflammation. Application of a potent S. hominis-AMP+ to a mouse model of AD with a filaggrin mutation (FLGft/ft) showed reduced SA survival, suppressed proinflammatory and Th2 cytokines, enabled host AMP (Camp) expression, and improved inflammation. In a human trial, 41 AD subjects were screened for CoNS-AMP+ from their own microbiome. Consistent with previous observations, only 14 were identified with CoNS-AMP+ clones. These clones were from diverse species including S. epidermidis, hominis, capitis and warneri. Subjects were then randomized in a double-blind placebo controlled trial for one week of BID application of 1×105 CFU/cm2 autologous potent CoNS-AMP+ (n=5), weakly active CoNS-AMT+ (n=3), or vehicle (n=6). SA colonization at the end of treatment on subjects treated with potent active strains was reduced by >90% compared to the baseline (P=0.013). Metatranscriptomic analysis suggests that the diversity of skin microbiome greatly increases after the treatment. Importantly, local EASI assessed on subjects that received potent CoNS-AMP+ clones was significantly improved compared to baseline (P=0.029) and persisted for several days after end of treatment. Subjects that received weak CoNS-AMT+ or placebo did not improve. These observations suggest that rational selection of targeted topical bacteriotherapies can be a useful strategy to treat some patients with AD.