Skin bacterial microbiome as clinical biomarker in atopic eczema
Diagnosis of atopic eczema (AE) severity is still today a
semi-quantitative clinical score based on subjective information from
the patients together with doctor’s subjective estimation on severity of
the skin lesions and patient’s history of itching and sleep
loss.67,68 In the era of targeted therapy, and thus
more complex therapy management requirements, more objective criteria
are urgently needed. A diagnostic biomarker would also have the
potential to differentiate between the different subgroups of AE. AE,
likewise, lacks a prognostic biomarker: AE69 affects
30% of children but only 5% of adults – thus the question remains who
keeps the disease, who emerges from it, and who embarks on the full
career of an atopic individual. Skin microbiome dysbiosis, measured
either as microbiome diversity or more reliably as abundance of S.
aureus , was shown to correlate with both the AE clinical score and the
expression of skin barrier molecules.70 It is still a
matter of scientific debate whether the relative frequency of various
bacteria (e.g., S. aureus frequency as obtained from 16S based
NGS) is an adequate biomarker or rather the absolute microbial load
(e.g., as obtained from qPCR) is better. Furthermore, is it enough to
quantify the DNA abundance from non-standardized amounts of skin
samples, or rather is the absolute microbial load of standardized skin
samples needed?
S. aureus is important for AE pathogenesis even though it is
still a matter of debate whether overgrowth of S. aureus is a
cause or a result of barrier disruption.71 Thus,
microbiome analysis, at least on the species level, but ideally on the
strain level, would enables us to identify personalized biomarkers. This
highlights a methodological drawback, as currently tools for annotation
on species level are not reliable. Furthermore, the current methods for
skin microbiome measurement are not standardized; testing the same
material in different laboratories is prone to give different results.
For skin microbiome to be used clinically as a biomarker, standardized
methodology needs to be developed and validated so it can be reliably
used across different laboratories.72 Combinatory
biomarkers between skin microbiome and biomarkers of type 2 immunity
would also be of great potential.73 Recently, biofilm
propensity of S. aureus skin isolates – as a cause and possible target
has become more and more of a central issue.74 Thus,
resolving the enigma of skin-microbe interaction as a function of skin
homeostasis has to take more players into the.75
In conclusion, skin bacterial microbiome shows great potential to be
used as a clinically important biomarker for atopic eczema. To reach
this aim, we need to perform prospective clinical trials and large
longitudinal registries that include skin microbiome testing.
Furthermore, it is critical to advance standardized and foremost
quantitative methodologies for skin bacterial microbiome analysis. New
technologies, such as single molecule real time , need to be further
developed and tested in order to improve skin microbiome analysis with
higher accuracy and/or longer sequencing length. Collaboration between
large academic consortia and pharmaceutical companies is essential for
such endeavors.