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Could the Human Virome be the Next Skin Care Target?

Contact Author Marisa Meloni, Ph.D., and Roberto Ferrari, Ph.D., VitroScreen; John Jiménez, Belcorp Colombia; and Rachel Grabenhofer, Cosmetics & Toiletries
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Editor’s/authors’ note: The topic of the human virome is new, difficult and somewhat dangerous. In this moment, the scientific community around the world is making tremendous effort to discover therapies to produce a vaccine for COVID-19. As such, cosmetic scientists are advised to remain humble as this new and unfamiliar territory is uncovered.

According to John Jiménez, senior exploration scientist at Belcorp, Colombia, with the COVID-19 outbreak and responding influx of hand sanitizer and cleanser formulations, personal care products making antiviral and disinfectant claims are especially hot right now, as you might expect.

“I [recently attended] ... a webinar that showed several products specifically communicating virus protection,” Jiménez told Cosmetics & Toiletries. Examples ranged from sanitizing room spray and surfacing cleansing wipes, to laundry detergent and hand soaps. “The projection, I think, is that many cosmetic companies will begin to launch products with [related] claims and R&D departments need to understand more about this claim. I think this is the beginning.”

Jiménez and Cosmetics & Toiletries therefore sought experts researching this novel field to comment on the human virome as a potential skin care target. Following are their responses.

What is the human virome? How is it organized on the skin?

Besides bacteria, the human microbiome also includes viruses and fungi; the virome and mycobiome, respectively. Therefore, the human virome is a collection of all the viruses found in or on human organs—such as the skin—and including both eukaryotic (organisms whose nucleus are enclosed within membranes) and prokaryotic (organisms lacking a membrane-bound nucleus) infecting viruses.

Eukaryotic infecting viruses clearly have important effects on human health, ranging from mild, self-limited acute or chronic infections, to those with serious or fatal consequences. Prokaryotic infecting viruses (i.e., bacteriophages or simply phages) can also influence human health by affecting and orienting the bacterial community’s structure and function.1, 2 Therefore, the virome surely plays a role in the way microbes affect human health and disease.1

Concerning the human skin microbiota composition, we know that viruses make up the majority; however, their role in skin health and appearance is almost unknown. In fact, the few affords thus far spent on understanding the virome have been mostly focused on pathogenic and high virulent virus strains, especially given the current high cost of molecular science. Nevertheless, these few studies have allowed science to discover the presence of human viruses associated with skin cancers and a range of cutaneous manifestations.

Despite the importance of the human skin virome, the current knowledge of its role is very little, and its organization and interactions with host microbiome are poorly understood. In the context of the COVID-19 pandemic, we expect this topic will be addressed at a basic research level thanks to technological advances to explore, in depth, skin in good health that accounts for the human virome.3

Science has identified that different types of viruses exist, similar to bacteria. Are there "good" viruses for the skin?

All viruses present onto the human skin are pathogenic to some organism but when a scientist talks about “good” viruses, this usually refers to bacteriophages. These phages exploit bacteria cells to death for their replication and multiplication. However, in some situations, bacteriophages can benefit specific bacterial species with a probiotic effect on human health.

One example is in the intestines, where resident bacterial of the gut microbiota can be infected by phages. Rather than quickly replicating inside of cells and causing them to burst, they remain in a pro-phage stage, incorporating their genetic code into the bacterium genome and awaiting the reactivation of their lytic cycle in the presence of specific environmental stimuli.

In such a “standby” situation, a symbiosis between the two microorganisms is set: on one side, the bacterium provide protection to the virus genetic code and on the other side, the virus provides the bacterium with a new set of genes that may augment the cell fitness in the environment by broadening its niche.4 Once the viral genome has been integrated into a bacterium DNA, the viral genetic material also can be transferred between individual bacteria.5

As a host, skin has been studied for potential interaction with bacteriophages. In particular, speculation has been made about the possible utilization of phages in prebiotic therapies. One study in 2020 has highlighted the importance of bacteriophages on psoriasis lesional skin. More specifically, this study identified the presence of a biological correlation between a specific skin virome composition and psoriasis lesions.

In addition, two differentially abundant phage species—Acinetobacter phage Presley and Pseudomonas phage—have been shown to suppress host bacteria numbers, which are known to be linked to lesional skin wounds. These findings pave the way for the development of probiotic phage therapies for skin health in the case of psoriasis.6

Do the virome and microbiome interact? If so, how?

The virome and microbiome interact; this is a reality. But as of yet, we do not have robust evidence about this interaction on the skin. The main limitations in discovering this exciting and complex world are the types of techniques available to conduct this research.

Again, one example comes from gut virome. Here, a large number of viruses can be counted belonging to different families that can not only infect our own human gut cells, but also infect other commensal organisms, thus directly impacting our well-being.

Still, despite its predominance, the virome remains one of the least understood components of the gut microbiota. This is due to the absence of a full human virus genome database—for now. Luckily, costs are coming down to make new molecular research technologies more affordable and this will shorten the gap.

Based on its interconnectivity with all living cells, it is clear the virome cannot be studied in isolation but instead must be related to other organisms associated with the microbiome and human host cells as well. The gut virome and the gut bacterial microbiome share similar trajectories and interact in both human health and disease.7

The interaction between viruses and the microbiome happens mainly with bacteriophages, which kill commensal and pathogenic microbes; or via a symbiotic relationship between two microorganisms, through a genetic material exchange. Other forms of interactions may still occur and have yet to be validated.

In some situations, bacteriophages can benefit specific bacterial species with a probiotic effect on human health.

Recently, scientific publications have reported that individuals infected with COVID-19 also have skin afflictions. What are the most common manifestations on skin?

Virus infections involve our immunity and can induce a tremendous multi-component inflammatory cascade that can also impact skin health and appearance. This is confirmed by a paper that appeared in March 2020 based on the observation of COVID-19 patients in Italy: 20% of patients manifested skin modifications. No lesions were reported but exclusively rashes, redness and oedema. Furthermore, exanthematous eruptions potentially related to COVID-19 disease were highly variable and heterogeneous.8-10

COVID-19 is changing consumer habits. Just as the microbiome has represented a major trend in cosmetics R&D, could the virome be one of the next trends for cosmetics and skin care?

In our opinion, the knowledge of the microbiome’s role and its evolution on skin is still a big research topic; one could argue this will be endless. Surely the scientific knowledge and tools to explore the skin virome are much more sophisticated than those required to study a bacteria population.

As noted, viruses cannot be studied as single organisms, however; and they require the presence of a prokaryotic co-host or hosts. Therefore, it will not be enough to focus on the role of the virome in skin health, but rather the effect of specific microbiota as a whole living population. Cosmetic trends rely on claims that could be associated but because of the complexity of this microbial community, we think that we are far from this scenario.

Could it be feasible, in the future, for ‘cosmetic’ products to have action against specific virus strains? How might this benefit the skin? What is your opinion of an ‘antiviral’ or related claim for cosmetics?

These questions are related to regulatory issues; for example, products having activity on viruses…are maybe virucidal? This is beyond the definition and regulatory framework for cosmetics.

It is possible this could become a common claim in future sanitizing and cleaning products?

[No comment on the claim.] In relation, an effort should be made by all testing laboratories, either for clinical or preclinical testing, to develop and use validated and universally accepted experimental protocols for testing these alcohol-based solutions or gels.

Stay tuned as Cosmetics & Toiletries explores this subject further in future coverage.

 

References

1. Wylie, K.M., Weinstock, G.M. and Storch, G.A. (2012, Oct 1). Emerging view of the human virome. Translational Research. 160 (4) 283–290; doi: 10.1016/j.trsl.2012.03.006; PMC 3701101; PMID 22683423.
2. Grice, E.A., Kong, H.H., ... Segre, J.A., et al. (2009, May 29). Topographical and temporal diversity of the human skin microbiome. Science. 324(5931) 1190–1192; doi: 10.1126/science.1171700
3. Hannigan, G.D., Meisel, J.S., ... Grice, E.A., et al. (2015, Oct 30). The human skin double-stranded DNA virome: Topographical and temporal diversity, genetic enrichment and dynamic associations with the host microbiome. mBio. 6(5) e01578–15; doi:10.1128/mBio.01578-15; ISSN 2150-7511; PMC 4620475; PMID 26489866.
4. Newman, T. (2020, Jan 6). How 'good' viruses may influence health. https://www.medicalnewstoday.com/articles/327167
5. Holmes, R.K., Jobling, M.G. and Baron, S (ed) (1996). Medical Microbiology. 4th edn. University of Texas Medical Branch at Galveston. Galveston, TX. Bookshelf ID: NBK7908PMID: 21413277.
6. Wang, H., Chan, H.H., Ni, M.Y., Lam, W.W., Chan, W.MM. and Pang, H. (2020, e-pub 2019, Jun 24). Bacteriophage of the skin microbiome in patients with psoriasis and healthy family controls. J Invest Dermatol. 140(1) 182-190.e5; doi: 10.1016/j.jid.2019.05.023
7. Mukhopadhya, I., Segal, J.P., Carding, S.R., Hart, A.L. and Hold, G.L. (2019). The gut virome: The ‘missing link’ between gut bacteria and host immunity? Therap Adv Gastroenterol. 12: 1756284819836620; doi: 10.1177/1756284819836620
8. Recalcati, S. (2020, Mar 26). Cutaneous manifestations in COVID-19: A first perspective. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.16387
9. Galván Casas, C., Català, A., ... García‐Doval, I., et al. (2020). Classification of the cutaneous manifestations of COVID‐19: A rapid prospective nationwide consensus study in Spain with 375 cases. BJD. doi:10.1111/bjd.19163
10. Tang, K., Wang, Y., Zhang, H., Zheng, W., Fang, R. and Sun Q. (2020). Cutaneous manifestations of the Coronavirus Disease 2019 (COVID‐19): A brief review. Dermatologic Therapy; doi: 10.1111/dth.13528.
 

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