Skin microbiome changes in AD treatment
Treatment of AD flares reduces disease severity and decreases S. aureus relative abundances with concomitant increase in skin microbiome diversity including commensal skin flora such as Corynebacterium and Cutibacterium .55 Topical corticosteroids and bleach baths have also been associated with cutaneous microbiota composition on lesional skin temporarily resembling baseline or similar to non-lesional skin, although their microbiota remained distinctly different from healthy control skin.56, 57
More recent therapies have targeted specific inflammatory pathways. The Th2 inflammatory axis plays a key role in AD pathology.5 During AD pathogenesis, Th2 polarization leads to increased expression of the cytokines IL-4, IL-13 and IL-31.58, 59 These trigger proinflammatory responses promoting pruritus, reduced epidermal barrier function, increased transepidermal water loss, and skin inflammation. Skin barrier defects facilitate binding of S. aureus, while Th2 cytokine signalling inhibits anti-microbial peptide secretion by keratinocytes,18 potentially contributing to a vicious cycle of sustained inflammation in chronic AD.
One of the biologics targeting components of this inflammatory axis is dupilumab, a monoclonal antibody which blocks IL4 receptor alpha (IL-4Rα), leading to inhibition of IL-4/IL-13 signalling. Numerous clinical trials have shown that dupilumab is effective in alleviating AD symptoms and reduction in disease scores,60 and has been approved by the FDA for this purpose in both adults and children.61
Dupilumab therapy is associated with skin microbiome composition alterations as well. A double-blind, placebo-controlled clinical trial conducted by Callewaert et al demonstrated that adult patients had decreased S. aureus relative abundance and increased Shannon diversity as soon as four weeks after dupilumab treatment, correlating with clinical improvement measured by the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD) tools.62While clinical trials showed decreases in S. aureus abundance on patient skin, dupilumab treatment did not completely eradicate S. aureus . Instead, the abundance of S. aureus increased again 32 weeks post treatment.62 Treatment with tralokinumab, an anti-IL-13 monoclonal antibody, was also associated with reducedS. aureus abundance with concomitant increase in the relative abundances of CoNS in the lesional skin of adults with moderate-to-severe AD from the Phase 3 ECZTRA 1 trial [ClinicalTrials.gov ID NCT03131648].63 It is still unknown if these changes in microbiota composition merely reflect transient alterations in host skin barrier and immune status, or if these changes contribute to clinical improvement. Future mechanistic work will be helpful in determining if skin microbiome changes play a role in clinical response to biologics or merely reflect normalization of epidermal biology.