The role of the skin microbiome in rosacea

Rosacea is a common chronic inflammatory skin disorder characterized by chronic redness and inflamed papules and pustules affecting the central parts of the face, thickening of the nose and eye symptoms. The development of rosacea is believed to be multifactorial.1

In this article we will dive into the growing body of evidence that suggests the microbiome on the surface of our skin plays an essential role in the development and propagation of rosacea.2,3 The skin microbiome is the entirety of the micro-organisms living on our skin – it is mostly microbes, but also includes fungi, viruses and – important to this article – mites. Specifically, we focus on the role of Demodex mites, and on Bacillus Oleronius, and Staphylococcus epidermidis.

“Rosacea is a common chronic inflammatory skin disorder, and the development is believed to be multifactoral.

Rosacea skin mite have a problem

The following section isn’t for the fainthearted.  If you’re squeamish about delving into the details of exactly what lives on our skin, you may want to skip to the conclusion.

The presence of Demodex mites (D. folliculorum and D. brevis) are believed to contribute to the inflammatory process in rosacea. However, these mites – the most common parasite in humans – aren’t exclusive to people with rosacea. They’re rarely seen on the skin of babies but increase in number as we get older and are reported to be present on the skin in nearly 100% of elderly people (classified as individuals 65+ years old).3,4

Both D. folliculorum and D. brevis have a life cycle of 14-18 days. They live on our face, including our forehead, nose, chin, cheeks, scalp, neck and ears – and are equally present in men and women. D. folliculorum (0.3-0.4 millimeters long) is the most common of the two, living in clusters, with their rear end sticking out of our hair follicles. D. brevis is a bit shorter (0.2-0.3 millimeters) and only exist in our sebaceous gland. D. brevis mainly feed on sebum, the oily secretion of the sebaceous gland, but also on the cells lining our hair follicles and sebaceous glands.4

The cascade of inflammation in rosacea

If everyone has Demodex mites habitually living on their skin, why does their presence only trigger rosacea in some and not others? Well, if you find the answer to that question, you may be in the running for a Nobel Prize. Until then, this is what we know so far.

People with rosacea have a nearly six-fold increase in Demodex density (measured in mites per square centimeter) on their skin compared to age-matched people without rosacea.5 Demodex release chitin, an essential building block of the mite body, which can activate Toll-like Receptor 2 (TLR2).

If everyone has Demodex mites habitually living on their skin, why does their presence only trigger rosacea in some and not others?”

TLR2 is a receptor that sits on the surface of our skin cells and recognizes foreign and potentially harmful substances. When TLR2 is activated, this can initiate a cascade of inflammatory immune responses resulting in inflammation showing as particular symptoms in rosacea: papules, pustules, thickening of the nose and angiogenesis (formation of tiny blood vessels) with telangiectasias (dilated blood vessels near the surface of the skin, or spider veins) and chronic redness.2

Bacillus Oleronius and the leaking follicles

The Demodex mites host other microorganisms – bacteria Bacillus (B.) oleronius is one of these.

This tiny bacillus was isolated from the inside of a D. folliculorum. The study showed that antigens from the B. oleronius triggered an inflammatory response in patients with papulopustular rosacea. The researchers speculated that this was because B. oleronius living inside Demodex mites might be an unfortunate symbiosis for people with rosacea.

The vast number of mites might distend the follicles, making them leaky. And when the mites die, they may release antigens from the B. oleronius they’re hosting. These antigens can then reach critical levels, leaking through the follicular walls and triggering a chain reaction of inflammation in the skin surrounding the hair follicles and sebaceous glands, resulting in papules and pustules.6

Staphylococcus epidermidis – the abundant culprit

Staphylococcus (S.) epidermidis is another suspected culprit thought to contribute to the pathogenesis of rosacea. They’re the most abundant bacteria living on our healthy skin and they help protect skin integrity by inhibiting the growth of pathogenic bacteria – at times, including Staphylococcus (S.) aureus.

It has been shown that S. epidermidis is the only bacteria present in pustules in the skin of people with papulopustular rosacea.3 Furthermore, people with rosacea seem to host strains of S. epidermidis that differ from those without rosacea, as they secrete virulent factors that may trigger an inflammatory immune response and the onset of rosacea. Lastly, S. epidermidis antigens also activate the TLR2, fueling the inflammatory cascade, resulting in rosacea symptoms.2

What came first: the dysbiosis or rosacea?

This may only be the tip of the iceberg in this so-called dysbiosis, a dysfunctional and pathogenic microbiome living on (and in) the skin of people with rosacea. However, it is still unclear whether it is the dysbiosis that causes rosacea to develop, or whether the dysbiosis is the result of an overall altered skin micro-environment due to rosacea itself.1,2

Though, one thing is clear: there is a consensus that the cause of rosacea is extremely complex and multifactorial. Known factors include: UV light exposure; stress; extreme temperatures; stimulants such as alcohol and coffee; spicy food; and neurogenic dysregulation.1,7 The skin microbiome plays a significant part, which is emphasized by the fact that there is no single cure to this chronic skin disease. end

References

  1. Rainer BM, Kang S, Chien AL. Rosacea: Epidemiology, pathogenesis, and treatment. Dermatoendocrinol. 2017;9(1):e1361574.
  2. Two AM, Wu W, Gallo RL, Hata TR. Rosacea: Part I. Introduction, categorization, histology, pathogenesis, and risk factors. J Am Acad Dermatol. 2015 May 1;72(5):749–58.
  3. Holmes AD. Potential role of microorganisms in the pathogenesis of rosacea. J Am Acad Dermatol. 2013 Dec 1;69(6):1025–32.
  4. Lacey N, Kavanagh K, Tseng SCG. Under the lash: Demodex mites in human diseases. The Biochemist. 2009 Aug 1;31(4):2–6.
  5. Casas C, Paul C, Lahfa M, Livideanu B, Lejeune O, Alvarez‐Georges S, et al. Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation. Exp Dermatol. 2012;21(12):906–10.
  6. Lacey N, Delaney S, Kavanagh K, Powell FC. Mite-related bacterial antigens stimulate inflammatory cells in rosacea. Br J Dermatol. 2007;157(3):474–81.
  7. Choi JE, Di Nardo A. Skin neurogenic inflammation. Semin Immunopathol. 2018 May 1;40(3):249–59.

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