The skin microbiome
The “human microbiome” is among the biggest scientific and popular stories of the last decade. The “human microbiome” is the population of microbes living on and in us, now known to be essential for life and bodily function. As the microbiome underlies human health, it is of considerable interest in both medicine and consumer care (all those non-medical products like soap, laundry detergent, and diapers). Together, microbe-mediated technologies will impact more than $400 billion USD/year in consumer and medical spending. This leads to a lot of research interest.

Sampling skin is difficult due to dirt, oils, washing habits, and differences between people’s skin.  This led early studies to focus on gut (sampling feces is easier than you think). Also, skin is populated by different microbes, with a larger fraction being eukaryotes called fungi (and on skin, yeasts). Fungi have more complex genomes (a nucleus and chromosomes) and lifestyles than bacteria and are more complicated to study. To learn more about bacteria versus fungi, look here. These difficulties left the majority of human microbiome studies on gut and bacteria, leaving much unknown about skin and skin fungi. 

What is dandruff?
“Dandruff” and “Seborrheic Dermatitis” are the same, just different severity, with flaking and itching. More than 50% of people over 15 get it, but very few children.  Normal scalp skin is smooth. Dandruff is loosely attached flakes with itching, is only on scalp, and has no obvious redness (inflammation). Seborrheic dermatitis is more severe, with piled adherent flakes sometimes in beard, moustache, and eyebrows, often over reddened skin.   Dandruff requires three factors: fungi, sebum, and an “individual susceptibility” (meaning some people get it and others do not). 

The microbiome and “Koch’s Postulates”
Early disease research was based on “Koch’s Postulates”, developed in 1890, which defined disease as caused by “germs” (microbes):1.   The microbe must be found in all organisms with the disease, but not in healthy organisms.2.   The microbe must be isolated from a diseased organism and grown in pure culture.3.   The cultured microbe should cause disease when introduced into a healthy organism.4.   The microbe must be re-isolated from the inoculated, diseased experimental host and identified as identical to the original microbe.Koch’s postulates led a renaissance of discovery and understanding and provided the framework for modern microbiology and germ theory. However, new technologies have upped the game, unlocking a world of unknown complexity, including “unculturable” organisms and insight into interactions between microbes and with the host. Further, it is no longer considered ethical to infect “healthy” humans with known pathogens. This complexity led to difficulties with application of Koch’s postulates. 

Fungi – the “forbidden kingdom”
One difficulty with Koch’s postulates is fungi. The same fungus can be benign, helpful, or cause disease. An example is aspergillus. Aspergillus particles are ubiquitous and we inhale them with every breath. However, few healthy individuals develop pulmonary aspergillosis. Fungi are notoriously difficult to culture, and their similarity to human cells makes design of anti-fungal treatments complex. Hence, research into fungi and disease lags behind that of bacteria and infection.

Malassezia
The vast majority of evidence supports a role of Malassezia in scalp health. While all humans have Malassezia, experiments in the 1960’s and ‘70’s clearly support fungal involvement. Nystatin, an anti-fungal with low anti-bacterial activity, was compared to neomycin or tetracycline, specific anti-bacterial agents. They show removal of fungi decreases dandruff, removal of bacteria does not, removal of both is the same as antifungal treatment alone, and reintroduction of resistant Malassezia causes dandruff to return. 

These data fulfill 3 of 4 of Koch’s postulates. Only postulate 1 is not fulfilled, as all humans carry Malassezia. Even Koch himself knew postulate 1 could remain unfulfilled, as he observed in asymptomatic cholera carriers.

Individual susceptibility
Malassezia are on all humans, even those without dandruff. This led to the hypothesis of “host susceptibility”, proven by a study where dandruff and non-dandruff individuals were treated with a Malassezia metabolite, oleic acid. Oleic acid induced dandruff in susceptible individuals but not non-susceptible. This defines an underlying “susceptibility” predisposing dandruff, likely due to differences in skin permeability. 

Sebum
The need for sebum is supported by: 1) correlation with sebaceous gland activity, 2) dandruff occurrence exclusively on sebum rich areas, and 3) a model of dandruff showing a requirement for both sebum and Malassezia.

Sebum is a mixture of triglycerides, fatty acids, wax and sterol esters, cholesterol, and squalene. When secreted, sebum is triglycerides and esters which are then broken down by microbes into glycerol and free fatty acids. Sebum is also responsible for the stress and hormone related increase in dandruff, it being well known they effect sebum secretion and impact dandruff.

Summary
It is now clear that scalp Malassezia negatively impact scalp health, breaking down sebum into toxic unsaturated fatty acids which induce flaking and inflammation in susceptible individuals. This classifies them as “pathogens” or as “commensal opportunistic pathogens”.More research is required on Malassezia to fully elucidate the role of the microbiome and immunity in microbe-mediated disease. As new pathways are found, new intervention targets arise. The new, groundbreaking research in microbiomes, commensalism, and pathogenesis will enable new treatment technologies which may not depend on broad spectrum antifungals. 

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