634 Address all correspondence to Thomas Dawson, thomas_dawson@asrl.a-star.edu.sg The Role of the Scalp Microbiome in Health and Disease: Malassezia, Friend or Foe? THOMAS L. DAWSON, JR A*Star Skin Research Laboratories, Skin Research Institute, Singapore, Singapore Department of Drug Discovery, Medical University of South Carolina, USA (T.L.D.) Synopsis The human microbiome has soared to scientific celebrity status, while the skin microbiome has been somewhat dragging behind. We now understand that microbiomes are central to humanity, with the human body consisting of more microbes than human cells and the microbes both being essential for maintenance of life and regulating diverse functions such as digestion, obesity, blood pressure, skin disease, and even brain function, mood, and personality. While the skin microbiome has lagged in investigation and understanding, we now know it influences many facets of skin health, including acne, seborrheic dermatitis (dandruff), psoriasis, atopic dermatitis, and rarer disorders, including pityriasis versicolor and folliculitis. Bacteria rule the gut microbiome, but fungi play an important role in skin, particularly the dominant eukaryote Malassezia yeast. Malassezia are present on all humans (and all warm-blooded animals), including healthy and diseased skin. The Malassezia clade consists of 18 species with numerous functionally distinct subspecies and strains, and it remains unclear how the functional differences are involved in skin health. Historically, Malassezia have been considered “commensal” organisms, defined as those who derive a benefit from their host (humans, as their food source) but have no impact, either positive or negative. A “mutualistic” relationship is one in which both partners benefit, and a “pathogenic” one in which one benefits and one is harmed. Hence, commensalism is the default situation where there is limited data. Now, with more evidence, it is becoming clear that Malassezia likely have all three roles in human skin. INTRODUCTION Why would a talk on skin microbiome be important in a hair care conference? In this case, it results from the internal divisions of consumer care companies, with vertical sections based on product form. As dandruff is most commonly treated with shampoos, dandruff is a hair care issue, despite it being a disorder and treatment paradigm relating to the skin microbiome. It is obvious why we have skin—it keeps bad things out and necessary things, like water, in. Skin is our “space suit” protecting us from a hostile environment. But the skin is also completely different from a space suit, as it is a living entity replenished every 14 to 21 days and covered in a microbial “skin” of its own. As skin is complicated and this audience is focused on hair, skin warrants a bit of introduction. J. Cosmet. Sci., 72, 634–642 (November/December 2021)

635 THE ROLE OF THE SCALP MICROBIOME IN HEALTH AND DISEASE SKIN BIOLOGY Skin is a multilayered covering consisting of a “permanent” nonrenewing dermis covered by a continually renewing epidermis. The dermal layer is 2–3 mm thick, the epidermal layer 0.1–0.2 mm thick, and the overlying stratum corneum 10–20 μm. As the dermis is a nonrenewable layer, it ages along with our body and is primarily responsible for aging issues such as wrinkles and sagging. At the dermal or epidermal junction are stem cells that divide and differentiate into the tough outer stratum corneum, the sort of plastic wrap that covers our body. The entire epidermis will renew itself about every two months, but the stratum corneum should renew itself every 14 days. In “hyper proliferative” skin disorders such as dandruff, instead of renewing every 14 days, the stratum corneum will renew itself in only six or seven days (1). It is generally accepted that the microbiology on skin resides in the stratum corneum (2,3). However, skin consists of many different environmental niches. Forearm skin is dry, it does not have sebum, and it can be considered desert wasteland and challenging environment for microorganisms. But when we consider the scalp, we have heavy sebaceous secretions and hair occluding and holding in water. Thus, on the scalp, there is an optimal environment for microbiology (4,5). Another important consideration is we think of skin as a singular organ. If one were to remove the skin and spread it out, it would be about 2 m2, and, for many years, that is how it was considered. But if one considers the topography, follicular openings, invaginations, and ridges, the surface area is closer to 25 m2, on par with the gut and lung as a surface area for host–microbe communication (6). SKIN MICROBIOLOGY First, a few terms should be defined. A “microbiome” refers to the collection of microbial genomes present in a system. Hence, the “microbiome” does not do anything it is a means of identifying what organisms are present. The “microbial community” is the collection of organisms, living and dead, that functionally interact with the host environment, and each other. What is the microbiology living on or skin? There are on the order of 1–10 million microorganisms per cm2. One reason skin microbiology is considered an easier research is because it is easier to sample. You can use a swab, tape strip, cup scrub, or even a q-tip and sample right off the skin’s microbiome. It is also complicated by the specific environment, immune system, and sex, and many sites are completely structurally different. As one reads and learns about the skin microbiome, it is imperative to understand where people are sampling, what they are looking at, and how they are looking at it (3,7). After sampling, the primary method for microbiome analysis is nonculture-based next- generation DNA sequencing, usually by one of two methods: amplicon or metagenomic. In amplicon sequencing, DNA is isolated from the sample and amplified via PCR to isolate unique microbial genomic regions. The resulting sequences are compared to existing databases to identify and count the different genomes. The primary insufficiencies with amplicon sequencing are that there may be microbes that are not amplified, as they are too different, fall out of consideration because of amplification bias, or do not exist in the