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INVESTIGATIVE REPORT Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV

Temporal Stability of the Healthy Human Skin Microbiome Following Dead Sea Climatotherapy
Michael BRANDWEIN 1, 2 #, Garold FUKS 3, 4 #, Avigail ISRAEL 2, Ashraf AL-ASHHAB 2, Deborah NEJMAN 7, Ravid STRAUSSMAN 7, Emmilia HODAK 5, Marco HARARI 2, 6, Doron STEINBERG 1, Zvi BENTWICH 2, Noam SHENTAL 3 and Shiri MESHNER 2
1
Biofilm Research Laboratory, Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Jerusalem,
2
The Cutaneous Microbiology Laboratory, The Skin Research Institute, The Dead Sea and Arava Science Center, Masada, 3 Department of Mathematics and Computer Science, The Open University of Israel, Raanana, 4 Department of Physics of Complex Systems and 7 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 5 Department of Dermatology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, and 6 DMZ Medical Center, M. P. Dead Sea Ein Bokek, Israel
#
These authors contributed equally to this work.
Dead Sea climatotherapy( DSC) is a therapeutic modality for a variety of chronic skin conditions, yet there has been scarce research on the relationship be tween the cutaneous microbiota and disease states in response to DSC. We characterized the skin bacterial and fungal microbiome of healthy volunteers who underwent DSC. Bacterial community diversity remained similar before and after treatment, while fungal diversity was significantly reduced as a result of the treatment. Individuals showed greater inter-individual than temporal bacterial community variance, yet the opposite was true for fungal community composition. We further identified Malassezia as the genus driving temporal mycobiome variations. The results indicate that the microbiome remains stable throughout DSC, while the mycobiome undergoes dramatic community changes. The results of this study will serve as an important baseline for future investigations of microbiome and mycobiome temporal phenomena in diseased states.
Key words: skin microbiome; skin mycobiome; climatotherapy. Accepted Aug 16, 2017; Epub ahead of print Aug 17, 2017 Acta Derm Venereol 2018; 98: 256 – 261.
Corr: Shiri Meshner, The Cutaneous Microbiology Laboratory, The Skin Research Institute, The Dead Sea and Arava Science Center, Masada 8693500, Israel. E-mail: shiri. meshner @ evogene. com and Noam Shental, Department of Mathematics and Computer Science, The Open University of Israel, POB 808, Raanana 4353701, Israel. E-mail: shental @ eponu. ac. il

The introduction of 16S amplicon sequencing, followed by whole-genome shotgun sequencing, has added new layers of understanding to our knowledge of skin commensals and pathogens. Whereas site-specificity of microorganisms on skin had been known for decades( 1), skin microbiome studies have enabled a clearer elucidation of skin habitats and their resident bacteria( 2, 3). In addition, the degree of temporal stability of the human skin microbiome has been expounded through both 16S and metagenomics studies( 4, 5). With this knowledge in hand, many groups have moved on to elucidate cutaneous microbial community perturbations in a myriad of disease states, including atopic dermatitis( 6, 7), acne vulgaris( 8, 9), psoriasis( 10), vitiligo( 11) and Leishmaniasis( 12).

Recent studies on skin-resident microbiota have expanded to include fungal species. Importantly, community differentiation based on biogeographical sites is less pronounced in fungi than in bacteria, with only specieslevel classification allowing for such distinctions( 13). Metagenomic studies have shown that the mycobiome is stable over time, much like the microbiome( 5), while amplicon-based studies, usually acquired by amplifying the internal transcribed spacer region( ITS) of the ribosome, have shown that community diversity converges from childhood to adulthood( 14). To the best of our knowledge, neither method has been used robustly to explore the connection between skin disease states and the mycobiome.
Dead Sea climatotherapy( DSC), or the combined effect of milder ultraviolet A( UVA) and ultraviolet B( UVB) radiation, Dead Sea baths, atmospheric bromide and magnesium, and relaxation has been shown to be an effective treatment for several skin diseases( 15). Benefits of DSC over alternative treatment methods include longer remission periods, rare side-effects, and psychological improvement( 16 – 18). In addition, DSC can be a more economic treatment method than expensive biologicals( 17, 19). Even.-Paz et al.( 20) showed that the main therapeutic element of DSC is sun exposure, with Dead Sea water baths potentially enhancing the effects of the sun. Subsequently, Kudish et al.( 21) showed that UVB solar radiation is attenuated in the Dead Sea basin, such that“ incident solar UVB has a higher ratio of therapeutic to erythema radiation relative to other sites”. We hypothesized that clinical improvements in patients undergoing DSC are accompanied by microbial community shifts similar to those observed with other treatment methods. However, before examining the skin microbiome of diseased individuals in response to DSC, we aimed to characterize the degree of stability of the skin bacterial and fungal microbiome of healthy individuals, in an attempt to isolate the effect of the clinical therapeutic element from the environment. doi: 10.2340 / 00015555-2769 Acta Derm Venereol 2018; 98: 256 – 261
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.