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Retinoids & the Skin Microbiome


Retinoids & Skin Microbiome

Abstract

Retinoids refer to a variety of topical vitamin A-based products used on the skin, they are used to treat mild acne and as a preventative measure to reduce signs of ageing. Despite widespread usage and prescription by doctors, the full effects on the skin microbiome are unclear. Since the skin microbiome has an essential function in the health of the skin, understanding this further is critical. In this article, we will explore the evidence defining the relationship between retinoids and the skin microbiome.

In summary, we find that studies suggest that Vitamin A and its metabolite may aid the self-regulatory process of the skin microbiome. However, we also need to be aware of the limitations of these studies, and consequently the need to conduct further studies in order to explore the questions which are still left unanswered. What are Retinoids?

“Retinoids” is an umbrella term referring to a variety of vitamin A-based products used on the skin. Retinoids are available over-the-counter in weaker strengths in the form of creams, gels and serums to be applied directly on the skin, and are generally used to treat mild acne and used as a preventative measure to reduce signs of ageing. Prescription-strength treatments are also available, usually to treat moderate to chronic skin conditions. How are Retinoids Used?

A lack of Vitamin A is associated with increased susceptibility to skin infection and inflammation (Chen et al, 2019), particularly as a result of an increase in the population of bacteria such as Staphylococcus aureus which become dominant within the skin (Wiedermann et al, 1996). Therefore, retinoids could have the potential to be beneficial for skin health by ensuring the skin barrier and microbiome are in check. Retinoids work by increasing blood flow and boosting skin cell turnover, therefore accelerating the cell renewal process and preventing dead skin cells from clogging pores, which may ultimately help the skin to repair itself quicker and reduce inflammation. However, retinoids are also known to potentially cause an initial ‘skin purging’ period (Leyden et al, 2017), where irritation may occur within the first few weeks but then later subsides, which can be an alarming and uncomfortable experience. Retinoids are well known for their benefits in reducing the signs of ageing by targeting fine lines, wrinkles, and pigmentation. Retinoids are advised to be used by individuals in their mid-twenties as a preventative measure, aimed at slowing down the natural ageing process by increasing the production of collagen and stimulating the production of new blood vessels in the skin.

Yet it is important to highlight that retinoids are not typically considered a “quick fix” solution, as optimal results generally require a certain level of consistency and patience. In general, improvements are expected to begin to become visible within 3-6 months of regular use, while the best results are expected to take closer to 12 months. Skin Microbiome and Retinoids

The skin microbiome is made up of an organic ecosystem of trillions of bacteria that sit on the surface of the skin. It acts as the first line of defence against the outside world and works in a team to keep your skin healthy by fighting infection, supporting the immune system, healing wounds and controlling inflammation. In order for the skin microbiome to be at its healthiest, it needs to be balanced with a high diversity of bacteria populating the skin.

Retinoids are generally acknowledged to be quite harsh treatments, and so it is necessary that the potential effects their use may have on the skin microbiome are explored to ensure overall skin health is not compromised. Current Studies Linked to Retinoids

Studies have suggested that Vitamin A and its metabolite can maintain the homeostasis of the skin microbiome, by regulating the innate immune system in a number of ways (Silvestre, Sato, & Reis, 2018).

The key elements of the innate immune system in the skin are Toll-like receptors (TLRs), these TLRs act as a guard by recognising and fighting off pathogenic bacteria. In the skin, Vitamin A deficiency means that certain TLRs (specifically TLR2 and TLR3) are unable to function normally and cannot recognise any potentially bad bacteria growing on the pores or hair follicles. Additionally, sometimes TLRs do not activate until there is a certain number of pathogens reached (Roche & Harris-Tryon, 2021).

Studies have suggested this could indicate a potential link between Vitamin A deficiency and skin conditions such as psoriasis and atopic dermatitis (Chen et al,2019). Topical retinoids can activate these TLRs so that they are able to function effectively, and therefore the use of retinoids may have therapeutic benefits in skin and hair regeneration (Kim et al, 2019). Next Steps for Research

While we know that retinoids alter the skin microbiome and the potential benefits are clear, current research does not explore the specific strains of microbes that derive benefits from retinoid use and the impact this has on microbial diversity. In order to have a clearer and fuller understanding of the effects of retinoids on the skin microbiome, more focused studies are clearly necessary. Sequential is a testing company with years of expertise in the field of skin microbiome and genetics. We utilise deep molecular analysis and next-generation sequencing (NGS) technology to understand the impact on an individual’s microbiome from products they use, and the effect from their environment.

All of our testing is carried out in-vivo and with the utmost care for unearthing the secrets that lie on the surface of the skin. If you are interested in carrying out any research with us and testing products, you can reach us at team@sequential.bio.


Lexicon

Skin Microbiome: refers to the collection of genomes from all the microorganisms in the environment (on your skin).

Retinoids: a catch-all for an array of vitamin A-based products used on the skin, used to treat mild acne and reduce fine lines and wrinkles.

Bacteria: bacteria are single-cell organisms that live everywhere on earth, including on the surface of the skin.

Homeostasis: the self-regulating process by which biological systems maintain stability while adjusting to changing external conditions.

Staphylococcus aureus (S.aureus): S. aureus is a key bacterium, typically considered to be harmful because it can cause skin infection as well as inflammation in the outer skin barrier.

Reference List

Chen, W., Zhao, S., Zhu, W., Wu, L. & Chen, X. Retinoids as an Immunity-modulator in Dermatology Disorders. Arch Immunol Ther Exp (Warsz) 67, 355-365, doi:10.1007/s00005-019-00562-5 (2019).

Eichner, R. Epidermal effects of retinoids: in vitro studies. J Am Acad Dermatol 15, 789-797, doi:10.1016/s0190-9622(86)70235-1 (1986).

Harris, T. A. et al. Resistin-like Molecule alpha Provides Vitamin-A-Dependent Antimicrobial Protection in the Skin. Cell Host Microbe 25, 777-788 e778, doi:10.1016/j.chom.2019.04.004 (2019).

Idres, N., Marill, J., Flexor, M. A. & Chabot, G. G. Activation of retinoic acid receptor-dependent transcription by all-trans-retinoic acid metabolites and isomers. J Biol Chem 277, 31491-31498, doi:10.1074/jbc.M205016200 (2002).

Kim, D. et al. Noncoding dsRNA induces retinoic acid synthesis to stimulate hair follicle regeneration via TLR3. Nat Commun 10, 2811, doi:10.1038/s41467-019-10811-y (2019). Leyden, J., Stein-Gold, L. and Weiss, J. Why topical retinoids are mainstay of therapy for acne. Dermatology and therapy, 7(3). 296-297, doi:https://doi.org/10.1007/s13555-017-0185-2 (2017).

Leyden J, Stein-Gold L, Weiss J. Why Topical Retinoids Are Mainstay of Therapy for Acne. Dermatol Ther (Heidelb). 2017 Sep;7(3):293-304. doi: 10.1007/s13555-017-0185-2. Epub 2017 Jun 5. PMID: 28585191; PMCID: PMC5574737.

Piipponen, M., Li, D. & Landen, N. X. The Immune Functions of Keratinocytes in Skin Wound Healing. Int J Mol Sci 21, doi:10.3390/ijms21228790 (2020).

Rittie, L., Varani, J., Kang, S., Voorhees, J. J. & Fisher, G. J. Retinoid-induced epidermal hyperplasia is mediated by epidermal growth factor receptor activation via specific induction of its ligands heparin-binding EGF and amphiregulin in human skin in vivo. J Invest Dermatol 126, 732-739, doi:10.1038/sj.jid.5700202 (2006).

Roche FC, Harris-Tryon TA. Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative Review. Nutrients. 2021 Jan 21;13(2):302. doi: 10.3390/nu13020302. PMID: 33494277; PMCID: PMC7909803.

Silvestre, M. C., Sato, M. N. & Reis, V. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis. An Bras Dermatol 93, 242-250, doi:10.1590/abd1806-4841.20186340 (2018).

Schroeder, M. & Zouboulis, C. C. All-trans-retinoic acid and 13-cis-retinoic acid: pharmacokinetics and biological activity in different cell culture models of human keratinocytes. Horm Metab Res 39, 136-140, doi:10.1055/s-2007-961813 (2007).

Wiedermann, U. et al. Vitamin A deficiency predisposes to Staphylococcus aureus infection. Infect Immun 64, 209-214, doi:10.1128/iai.64.1.209-214.1996 (1996).

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