“Without fungi humans could not exist.”
Lynne Boddy MBE FRSB FLSW. Professor of Microbial Ecology at Cardiff University.
Fungi first appeared over one billion years ago, and are fundamental for the breakdown of organic matter and recycling of nutrients[1]. There is a tendency to think of fungi as a group of not-so-nice spore-producing organisms that feed on organic matter. However, in reality, fungi are far more yin and yang species.
Fungi yin and yang
Some fungi appear to us as very dark – so very yin – as they smell unpleasant and can even be poisonous and deadly, or may be responsible for skin ailments such as ringworm and athlete’s foot[3]. On the other hand, an example of a yang fungi is a truffle – the fruiting body of the subterranean Ascomycetes fungi – some of which are sort after as valuable gastronomic delicacies.
However, fungi are much more than the large mushroom and toadstool fruiting bodies. Fungal genera also include moulds and yeasts, such as Malassezia and Candida. Penicillium mould, for example, has proven to be very yang. Without Saccharomyces cerevisiae there would be no fine wine to compliment the taste of truffle and arguably, as nature’s digesters of keratin, many keratinophilic moulds are also yang. In the cosmetic world, the yeast Candida albicans and mould Aspergillus brasiliensis are yang when used to test preservative efficiency in the ‘challenge test’[2], but yin when they are the cause of product spoilage or infection.
Skin mycobiome
Fungi are ubiquitous but, interestingly, they are only found in low abundance when present on and within humans. Fungi comprise just 0.001–0.1% of the gut microbiome, but they do represent a more significant percentage of metagenomic sequences on human skin, at 5–10%[4]. One study identified 7 fungi phyla and 112 genera; Basidiomycota phylum was the most prolific at 83.75%, of which Malassezia made up 80.3%[5]. Malassezia is another well-documented member of the human skin microbiome that is normally innocuous but has a critical role in skin conditions such as dandruff, seborrhoeic dermatitis (including baby’s cradle cap), tinea versicolor, and fungal acne[6]. It has been estimated that in total, around 10 million Malassezia globosa can be found living on our heads.
The persistence of fungi – even at the low levels found in the gut – suggests that they have evolved and adapted to exist by conferring an advantage, but whether the advantage benefits both the host and the fungi, or just the fungi, is unclear. Being such a tiny part of the gut microbiome, it is hard to believe that they play a crucial role. However, the greater presence observed in the skin microbiome does suggest their existence has an important function.
One key area of interest is the fungi life cycle. For example, keratinophilic fungi can use keratin as their sole source of carbon and nitrogen. This group includes 40 species of dermatophytes, which depend on keratin for growth[6]. Keratinophilic fungi can be transmitted through contact, picked up from soil, and from many other surfaces. The affinity of these fungi for keratin keeps them localized on hair, nails, and the outer skin. When sufficient in number, they cause dermatophytosis and trigger symptoms such as rashes, itching, and scaling. In response to itching, we scratch and so detach and return the fungi, complete with their keratin, to the environment[7]. As the average human sheds 4 kg of skin cells every year, it is easy to see how certain keratinophilic fungi could have strategically evolved to encourage us to scratch so that they can harvest their food from us, rather than having to live within the skin microbiome. Keratinophilic fungi could, therefore, be thought of as fundamental for the breakdown of detached skin cells and so are essential players in biodegradation and the recycling of nutrients[8]. This means that they may not necessarily be essential for maintenance of a healthy skin microbiome.
Malassezia
There are 14 members of the Malassezia genus (formerly known as Pityrosporum): M. furfur, M. pachydermatis, M. sympodialis, M. globosa, M. obtusa, M. restricta, M. slooffiae, M. equina, M. dermatis, M. japonica, M. nana, M. capre, M. yamatoensis and M. cuniculi. The 13 lipophilic Malassezia include both commensal and pathogenic species. Malassezia species are the largest population of non-host eukaryote cells that live in the skin microbiome[11]. They require a source of fatty acids to survive, as they are unable to synthesize their own. They depend on lipids for growth so, unsurprisingly, flourish near sebaceous glands found on the core body, arms, face and scalp. Virulence factors of Malassezia include high affinity for oily surfaces and the ability to produce biofilms. Malassezia species use a number of different lipases and phospholipases to break down sebum (which includes complex oils and waxes such as triglycerides, squalene, cholesterol and cholesterol esters, and wax esters)[9]. It is the products of these enzymes that induce inflammation and make Malassezia an exacerbating factor, but not necessarily the primary cause, of seborrheic dermatitis.
Malassezia is also associated with hypo- and hyper-pigmentation, such as in pityriasis versicolor (tinea versicolor), as well as dandruff and fungal acne. M. globosa and M. restricta are the scalp microbes most commonly associated with dandruff. However, M. furfur can contribute to a mild form of seborrheic dermatitis on the scalp, which can then lead to the symptoms of dandruff[10]. Dandruff is seen when rapid growth of the microbes triggers faster desquamation. Interestingly, dandruff severity relates not so much to the species of fungi, but more to the balance of bacteria (Cutibacterium and Staphylococcus) and thus to bacterial responses to host factors, such as sebum quality and moisture. In the battle for survival and supremacy on the scalp, Cutibacterium produces bacteriocins to suppress the growth of Staphylococcus, while Staphylococcus busily tries to out-populate Cutibacterium. Sebum, transformed by Malassezia, feeds these armies. Research shows that the severest dandruff occurs when Staphylococcus gets the upper hand[12].
Fungal acne
Malassezia is responsible for fungal acne, which is the rarer form of acne known to persist throughout typical acne treatments. Fungal acne occurs when Malassezia infects the pilosebaceous unit (that is, the hair shaft, hair follicle and sebaceous gland). The sebaceous glands become inflamed, forming large numbers of fine pustules (bumps with characteristic white heads). Fungal acne is often misdiagnosed as acne vulgaris or comedonal acne (blocked pores). Although fungal acne appears similar to acne vulgaris, which develops mainly on the face and upper body and manifests as breakouts of varying size that include both whiteheads and blackheads, fungal acne exhibits uniform red bumps that appear mostly on the upper body and arms, as well as the upper face (foreheads and temples). Sufferers may also have seborrhoeic dermatitis and dandruff. The Malassezia species typically involved in fungal acne are M. globosa, M. sympodialis and M. restricta. As mentioned previously, these yeasts are also members of healthy skin microbiota.
As with many skin ailments, factors that change the balance of microbes within the microbiome also trigger fungal acne. For example, malnutrition, taking immunosuppressors or antibiotics, using oily creams and the very humid conditions that occur following exercise can all trigger or exacerbate fungal acne. Fortunately, once correctly diagnosed, most sufferers can rebalance the skin microbiome and thus control fungal acne, with oral antifungals combined with acne treatments.
That Malassezia is present in dandruff, acne vulgaris and fungal acne, but is the main protagonist only in fungal acne, emphasizes further the interdependence of members of the skin microbiome and the consequences of their constant fight for survival. It seems some Malassezia species are Staphylococcus enablers in the fight for supremacy against C. acnes[12]. It has therefore been proposed, perhaps counter to traditional beliefs, that just as thehostility of C. acnes towards Staphylococcus modulates the microbiomes associated with severe dandruff and acne vulgaris[13], acne inflictions may be relieved by encouraging C. acnes to outcompete Staphylococcus and Malassezia. In the case of fungal acne, where Malassezia species have more fully infected the pilosebaceous unit, turning Malassezia from an exacerbating factor into the actual cause of the acne, could encouraging its usual competitors be a way of helping suffers fend off fungal acne?
Lynne Boddy’s quote on our dependence on fungi refers mainly to the yang role of fungi in recycling nutrients and their specialized relationship with plants, which is critical for food production. There is also no doubt that without the keratinophilic fungi, the 4 kg of skin cells shed every year by each of the 7.7 billion humans on our planet would be accumulating globally. However, sufferers of fungal acne experience the yin side of fungi. Their fungal yin troubles begin when the fine balance held within their healthy microbiome is disrupted to the advantage of Malassezia species.
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References
1. Loron, C.C. et al. Early fungi from the Proterozoic era in Arctic Canada. Nature 570, 232–235 (2019).
2. Guidelines: Cosmetic products: Notes of guidance for testing of cosmetic ingredients for their safety evaluation. The Rules Governing Cosmetic Products in the European Vol. 3 (Europa, 2000).
3. Havlickova, B., Czaika. V. A. & Friedrich, M. Epidemiological trends in skin mycoses worldwide. Mycoses 52, 95 (2008).
4. Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).
5. Scientists Complete Genome Sequence of Fungus Responsible for Dandruff, Skin Disorders (Science Daily, Spectrum Science Public Relations, 2007); https://www.sciencedaily.com/releases/2007/11/071106101200.htm
6. McBain, A. J., O’Neill, C. A. & Oates, A. Skin Microbiology – Reference Module in Biomedical Sciences
(Elsevier, 2016); https://www.sciencedirect.com/science/article/pii/B9780128012383992171
7. Keum H. L. et al. Structures of the skin microbiome and mycobiome depending on skin sensitivity. Microorganisms 8, 1032 (2020).
8. Sharma, R. & Rajak, R. Keratinophilic fungi: nature’s keratin degrading machines! Resonance 8, 28–40 (2003).
9. Park, M., Park, S. & Jung, W. H. Skin commensal fungus Malassezia and its lipases. J. Microbiol. Biotechnol. 2021 31, 637–644.
10. Rudramurthy, S. M. et al. Association of Malassezia species with dandruff. Indian J. Med. Res. 139, 431–437 (2014).
11. Thayikkannu, A. B., Kindo, A. J. & Veeraraghavan, M. Malassezia: can it be ignored? Indian. J. Res. Dermatol. 60, 332–339 (2015).
12. Xu, Z. et al. Dandruff is associated with the conjoined interactions between host and microorganisms. Sci. Rep. 6, 24877 (2016).
13. Kim, J. et al. Inferences in microbial structural signatures of acne microbiome and mycobiome. J Microbiol. 59, 369–375 (2021).
