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.