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.