Zinc Oxide’s Effect on the Skin Microbiome

I wondered for years why the only thing that could keep my atopic dermatitis under control was zinc oxide. Daily application of a physical sunscreen containing zinc oxide prevented recurring bouts of scaly, itchy, red patches of skin on my face, scalp, and hands. When I stopped using the sunscreen for a few days, the skin condition would aggressively return. I eventually stumbled upon a series of studies explaining how the microbes on our skin - our skin microbiome - interacted with our immune system and could cause the exact skin ailments I had been struggling with for years. S. aureus, in particular, can be a trouble-making bacterial species on the skin.

My obsession with the gut microbiome naturally extended into a passion for the skin microbiome: how dysbiosis (microbial imbalance) of the skin microbiome could weaken the skin barrier and cause different forms of atopic dermatitis and inflammatory skin conditions, similar to how dysbiosis of the gut leads to inflammatory systemic conditions.

What is the skin microbiome?

Just as the vagina, gut, mouth, anus, etc. are homes to trillions of microbial cells (bacteria, fungi, viruses), the skin - our largest organ (even sometimes considered a neuroendocrine organ) - is covered in trillions of microbes, living in a delicate balance that can either protect the skin barrier from pathogens, provide moisture, and prevent wrinkles; or wreak havoc, causing itchiness, redness, and inflammation. When the skin microbiome is in a state of homeostasis, it has powerful antimicrobial effects due to its constant communication with the host immune system.¹

However, when pathogenic species dominate, inflammatory skin conditions can arise. As mentioned earlier, S. aureus, is known for its inflammatory role in dermatitis. It has been shown to degrade proteins that protect the skin barrier; decrease the number of epidermal tight junctions; and respond to skin-produced neurotransmitters, neuropeptides, and cytokines with increased biofilm formation and toxin production.¹

Skin microbiota transplants (like fecal transplants but epidermal) hold the potential to change the skin microbiota composition. For example, non-odorous armpit skin microbiota communities have been transplanted into those with odorous armpit skin microbiota communities to reduce body odor (body odor results from sweat’s interaction with the microbes on our skin, not from the sweat itself).¹ Skin microbiota transplants have also been used to inhibit S. aureus in atopic dermatitis patients. Now that we know skin dysbiosis is a risk factor in skin conditions, we can use this knowledge to clinically manipulate the skin microbiome and provide relief to patients.

One novel treatment is the use of endolysins, virally-derived enzymes that target a specific bacterial species for destruction. Not only do endolysins targeted at S. aureus significantly improve eczema and atopic dermatitis symptoms, but endolysins could become an alternative to antibiotics. Endolysins are more targeted than current antibiotics (this reduces collateral damage and protects beneficial bacteria from being destroyed), and there is a minimal chance of bacterial species developing resistance to endolysins. With the steady rise in antimicrobial resistance, endolysins are an exciting and hopeful new option.

What are physical vs chemical sunscreens?

Before diving into how zinc oxide can alter the skin microbiome, I will briefly explain the different mechanisms of action by which physical vs chemical sunscreens work. Physical sunscreens contain zinc oxide, titanium dioxide, or a combination of the two; they work by reflecting UV rays, so the rays cannot penetrate the skin barrier and cause ROS-induced DNA damage. Chemical sunscreens, on the other hand, absorb UV rays into the skin where they are chemically converted into heat and released from the skin. If you have ever noticed that your skin feels hotter when you are wearing chemical sunscreen, this is likely why. Chemical sunscreens containing oxybenzone are also the sunscreens that are toxic to coral reefs. My decision to use a physical sunscreen over a chemical sunscreen was driven by the environmental advantage, but had the simultaneous benefit of healing my inflammatory skin conditions. Around this time, I began reading up on why zinc oxide was working wonders for my atopic dermatitis.

What are the benefits of zinc oxide?

Inflammatory skin conditions present with a weakened skin barrier and reduced ability to fight off pathogenic microbes. They often show an increased colonization S. aureus, and S. aureus may be responsible for the inflammatory symptoms of these skin ailments. Zinc oxide is an insoluble white powder known for its antimicrobial, antioxidant, and anti-inflammatory effects, often used topically for skin irritations, epidermal wound healing, and diaper rash.

Experiments have indicated zinc oxide’s ability to inhibit S. aureus in vitro.² The same studies have noted that the antibacterial activity of zinc oxide to inhibit S. aureus is enhanced by UV light in vitro; while zinc oxide and UV rays exhibit combined antibacterial effects on pathogenic microbes, the zinc oxide is also serving to protect the skin from UV light damage and the inflammation it can cause.² Zinc oxide has also been shown to inhibit S. aureus in vivo in mice, reinforcing the evidence that the topical application of zinc oxide makes for an effective antibacterial agent.³ Specifically, zinc oxide is thought to disrupt S. aureus biofilm formation by reducing the hydrophobicity index of the species.³

Other studies have looked at zinc oxide’s role in acne through its ability to reduce the abundance of P. acnes and regulate sebum production (which is thought to be dysregulated in acne).⁴

In conclusion, zinc oxide’s antimicrobial effects, in particular against S. aureus, could explain its ability to cure my inflammatory skin conditions of dysbiosis (microbial imbalance); it does so while simultaneously providing safe and effective sun protection. Future blog posts will delve deeper into endolysins’ ability to kill bacterial species and alleviate microbiome imbalances on the skin, rendering it an exciting potential antibiotic alternative.

References

1. Boxberger M, Cenizo V, Cassir N, La Scola B. Challenges in exploring and manipulating the human skin microbiome. Microbiome [Internet]. 2021;9(1):125. Available from: http://dx.doi.org/10.1186/s40168-021-01062-5  

2. Raghupathi KR, Koodali RT, Manna AC. Size-dependent bacterial growth inhibition and mechanism of antibacterial activity of zinc oxide nanoparticles. Langmuir [Internet]. 2011;27(7):4020–8. Available from: http://dx.doi.org/10.1021/la104825u  

3. Pati R, Mehta RK, Mohanty S, Padhi A, Sengupta M, Vaseeharan B, et al. Topical application of zinc oxide nanoparticles reduces bacterial skin infection in mice and exhibits antibacterial activity by inducing oxidative stress response and cell membrane disintegration in macrophages. Nanomedicine [Internet]. 2014;10(6):1195–208. Available from: https://www.sciencedirect.com/science/article/pii/S1549963414001142  

4. Abendrot M, Kalinowska-Lis U. Zinc-containing compounds for personal care applications. Int J Cosmet Sci [Internet]. 2018;40(4):319–27. Available from: http://dx.doi.org/10.1111/ics.12463  

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Introduction to the Microbiome