The role of the skin microbiome in skin pigmentation disorders 

The most visible facet of skin pigmentation conditions is that they affect the colour of the skin.

This occurs due to disruption of the skin pigment named melanin, which is made by specialized skin cells called melanocytes. When melanocytes become damaged or are unable to produce adequate melanin, or when melanocyte components accumulate in skin cells, lighter and darker patches can form on the skin surface.

‘Hyperpigmentation’ refers to darker patches produced by excess melanin, and ‘hypopigmentation’ refers to the lighter patches caused by too little melanin. Abnormal pigmentation can affect a specific part of the skin – for example, in the form of pigmented birthmarks, macular stains, hemangiomas and port wine stains – or the entire body, giving rise to skin pigmentation disorders such as vitiligo, pityriasis, albinism and melasma.

Skin pigmentation disorders have been linked to several health issues, but here we will explore current evidence around the role of the microbiome and emerging treatment options which seek to exploit this relationship. 

Skin pigmentation disorder development

The development of skin pigmentation disorders has been linked to dysregulation of the immune system and nutritional deficiencies. These processes can disrupt the production of melanocytes and lead to the accumulation of another melanin-producing component – known as melanosomes – within neighbouring skin cells.

The skin microbiota is known to play an essential role in maintaining skin homeostasis and in regulating our immune responses. It is thought that disruption to the skin microbiome could alter communication between the skin and immune system, leading to the emergence of the light or dark spots [1].

Research has already shown specific microbiota compositions and networks on the skin in association with differing pigmentation levels [1]. Skin microbiome disturbances have also been linked to gut microbiome disturbances, which have also been implicated in skin pigmentation disorders [2]. As well as helping to understand the causes of skin pigmentation disorders, this research, by Catherine Zanchetta and colleagues,  reinforces that the skin microbiome should be considered a target for skincare and clinical treatments [1].

Let’s explore in more detail with two specific skin pigmentation disorder examples where the skin microbiome has been implicated – vitiligo and pityriasis.

Vitiligo

Vitiligo is a chronic skin pigmentation disorder. Roughly 1–2% of the world’s population has vitiligo, and cases are equally spread out over all racial groups [3].

The main vitiligo symptom is complete loss of pigment in the skin, which results in lighter patches. It can occur on any area of the body and can affect small or large patches of skin. The most likely places for vitiligo to appear are in areas where sun exposure is frequent, including the hands, feet, face and arms, but it can also affect the head, mouth, eyes, groin and genitals [3,4].

Although there are no detrimental health effects associated, vitiligo has been shown to cause psychological distress in those who have the condition [5].

Role of the skin microbiome in disease development

Vitiligo is an autoimmune disease that occurs when a person’s immune system attacks their own melanocytes [6]. Although it is still not clear what triggers the process, evidence suggests that the gut–skin axis is involved.

Skin microbiome composition has also been shown to differ in vitiligo patients. Gene sequencing of the gut microbiome and metabolomic analysis using serum (the fluid component of blood) from vitiligo patients has also shown that the ratio of two key bacteria – Bacteroidetes and Firmicutes – is imbalanced in vitiligo patients, and revealed a correlation between several serum metabolites and specific microbial differences [7]. The bacteria Streptomyces and Streptococcus have also been found to be enhanced in active vitiligo (where there are new lesions or progression of existing lesions) compared to stable vitiligo (where there are no new lesions and no progression of existing lesions for at sustained period of time) [8].

In addition, the patchy loss of skin pigmentation that is characteristic of vitiligo arises due to loss of melanocytes in lesional skin. It is not known why melanocytes cannot re-pigment lesional skin, but it has been hypothesized that this may be due to an autoimmune attack on melanocytes. Although more research is needed, the skin microbiome may also play a role here – the skin microbiome in lesional skin is imbalanced, with decreased microbial diversity and uneven distribution [9]. So, even if the skin microbiome may not be a direct cause of vitiligo, this microbial dysbiosis may contribute to maintenance and severity of vitiligo through an interaction with the skin and immune system.

Treatment considerations

Currently there is no cure for vitiligo, but existing treatment options include covering smaller patches with long-lasting dyes, light-sensitive medicines, UV light therapy, corticosteroid creams, surgery and removing the remaining pigment from the skin (depigmentation) [10].

More work is needed to establish whether microbiome-targeted therapies (for example, the use of pre-, pro- or postbiotics) can offer a new treatment approach for skin pigmentation disorders such as vitiligo, but it offers an interesting avenue of research. A study using mice, for example, has shown that taking antibiotics can lead to skin depigmentation, which is accompanied by gut microbiome dysbiosis (but not skin microbiome dysbiosis). These results also indicate that dietary measures could be used to help support the gut microbiome and the immune system, consequently promoting skin health and preventing vitiligo onset or reducing the severity [11].

Bioactive ingredients, such as endocannabinoids, bioactive lipids, growth factors, microbiome modulators and antioxidant enzymes, have also been incorporated into cosmetic products to fight disorders such as vitiligo, as well as atopic dermatitis, uremic pruritus, eczema and acne. It is thought that these bioactives can help such conditions through the effects of catalase – a family of antioxidant enzymes – which can help reduce vitiligo through the re-pigmentation of skin (see ref. 12 for more information on how the bioactives work).

Pityriasis

Pityriasis, also known as tinea versicolor, is a common superficial fungal infection of the skin that manifests as hyper- or hypo-pigmented skin patches. Pityriasis is often confused with vitiligo, but vitiligo can normally be distinguished by an absence of scaling.

Role of the skin microbiome in disease development

It is actually the skin mycobiome – the skin’s fungal community – that has been found to play a causative role in the development of pityriasis. The fungi responsible for the disorder is Malassezia – specifically the species Malassezia furfur, Malassezia globosa and Malassezia sympodialis.

Malassezia fungi colonize the human skin after birth and are generally tolerated by the human immune system [13]. Although Malassezia are normal residents of the skin, the fungi can turn infective for a number of reasons, such as genetic predisposition, environmental conditions such as heat and humidity, immunodeficiency, pregnancy, oily skin and following the application of oily lotions and creams [14]. When this occurs, Malassezia fungi can invade the stratum corneum (the outer layer of the skin) and interact with the host immune system, as well as skin cell components such as keratinocytes and melanocytes. This can occur both directly and through chemical mediators released or triggered by the fungi, causing or contributing to disorders such as pityriasis [13].

Malassezia fungi are thought to inhibit melanocyte function and the making of melanin due to the production of dicarboxylic acids – such as azelaic acid – which can lead to de-pigmentation of the skin [15]. The fungi may also be involved in the development or worsening of other skin disorders, but a causative link between Malassezia and disease development has only been found for pityriasis so far, while its role in other conditions remains correlative [16].

Treatment considerations

The first-line treatment for pityriasis is topical antifungal therapy – namely the use of synthetic azole antifungals to reduce Malassezia skin colonization [13]. Yet harnessing the natural powers of the skin microbiome could provide more treatment options.

Malassezin, for example, is a natural organic compound produced by Malassezia furfur that decreases skin pigmentation – with early preclinical work indicating that it could have potential use as a treatment for facial hyperpigmentation following topical application [17]. Similarly, propionic acid, which is produced by the bacteria Cutibacterium acnes, has also shown promise as an effective and non-toxic alternative solution for hyperpigmentation [18] (see ref. 13 for a full review of Malassezia-related skin disease, and treatment options).

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References

1. Zanchetta, C. et al. Bacterial taxa predictive of hyperpigmented skins. Health Science Reports 5, e609 (2022).

2. Moustafa, M. A. A. Microbial Community of Human Skin and its Role Vitiligo Disease. Am. J. Biomed. Res. 12, 1 (2021).

3. https://www.verywellhealth.com/skin-pigmentation-disorders-5097370#citation-17

4. The United Kingdom National Health Service. Vitiligo.

5. Ramakrishna P, Rajni T. Psychiatric morbidity and quality of life in vitiligo patients. Indian J Psychol Med. 2014 Jul;36(3):302-3. doi: 10.4103/0253-7176.135385. Erratum in: Indian J Psychol Med. 2015 Jan-Mar;37(1):111.

6. Baldini E, Odorisio T, Sorrenti S, Catania A, Tartaglia F, Carbotta G, Pironi D, Rendina R, D’Armiento E, Persechino S, Ulisse S. Vitiligo and Autoimmune Thyroid Disorders. Front Endocrinol (Lausanne). 2017 Oct 27;8:290. doi: 10.3389/fendo.2017.00290.

7. Ni Q, Ye Z, Wang Y, Chen J, Zhang W, Ma C, et al. Gut Microbial Dysbiosis and Plasma Metabolic Profile in Individuals With Vitiligo. Frontiers in Microbiology. 2020;11.

8. Lu H, Xu J, Hu Y, Luo H, Chen Y, Xie B, et al. Differences in the skin microbial community between patients with active and stable vitiligo based on 16S rRNA gene sequencing. The Australasian journal of dermatology. 2021;62(4):e516-e23.

9. Ganju P, Nagpal S, Mohammed MH, Nishal Kumar P, Pandey R, Natarajan VT, et al. Microbial community profiling shows dysbiosis in the lesional skin of Vitiligo subjects. Scientific Reports. 2016;6(1):18761.

10. https://www.hopkinsmedicine.org/health/conditions-and-diseases/skin-pigment-disorders

11. Dellacecca ER, Cosgrove C, Mukhatayev Z, Akhtar S, Engelhard VH, Rademaker AW, et al. Antibiotics Drive Microbial Imbalance and Vitiligo Development in Mice. The Journal of investigative dermatology. 2020;140(3):676-87.e6.

12. Yang EJ, Hendricks AJ, Beck KM, Shi VY. Bioactive: A new era of bioactive ingredients in topical formulations for inflammatory dermatoses. Dermatologic therapy. 2019;32(6):e13101.

13. Saunte DML, Gaitanis G, Hay RJ. Malassezia-Associated Skin Diseases, the Use of Diagnostics and Treatment. Frontiers in cellular and infection microbiology. 2020;10:112.

14. Mehdi Karray WPM. Tinea Versicolor.  NCBI Bookshelf2022.

15. Nazzaro-Porro M, Passi S. Identification of tyrosinase inhibitors in cultures of Pityrosporum. The Journal of investigative dermatology. 1978;71(3):205-8.

16. Sparber F, LeibundGut-Landmann S. Host Responses to Malassezia spp. in the Mammalian Skin. Frontiers in immunology. 2017;8:1614.

17. Grimes P, Bhawan J, Howell M, Desai S, Coryell E, Einziger M, et al. Histopathological Changes Induced by Malassezin: A Novel Natural Microbiome Indole for Treatment of Facial Hyperpigmentation. Journal of drugs in dermatology : JDD. 2022;21(2):141-5.

18. Kao H-J, Wang Y-H, Keshari S, Yang JJ, Simbolon S, Chen C-C, et al. Propionic acid produced by Cutibacterium acnes fermentation ameliorates ultraviolet B-induced melanin synthesis. Scientific Reports. 2021;11(1):11980.

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