What's going on with all the microbes on our skin?
The paper in Nature online is here: http://go.nature.com/2BqvWUS
A dermatologist, a chemist, and an immunologist start a conference call. No, it isn’t a nerdy joke but how this review came to be. Recently, the human microbiome has become so commonplace that my patients talk about it. The idea that all of us harbor vibrant, dynamic ecosystems of microbes on our bodies, skin, mucosal, and gastrointestinal surfaces, with us since birth, is remarkable. These microbes are intimately associated with the epithelial surfaces where they reside and we are starting to understand how our resident microbes influence epithelial health, the immune system, and organs far away from epithelial sites, e.g. the brain.
There are many aspects to host microbiota interactions under investigation. For example, what are the identities of the different viruses, bacteria, fungi, and archaea that live on our bodies? How does microbiota composition change with time, geography, and personal habits? What interactions between different organisms determine the overall microbial composition? While these questions, and others, are valuable, we focused on one aspect of the skin microbiome– how do resident microbes interact with their host, and vice versa?
Early in the planning for this review, the three of us slipped into traditional categories of symbiotic associations and began to list examples of resident microbes that acted like mutualists, commensals, or pathogens. For a long time, most of us termed resident microbes, i.e. Cutibacterium (formerly Propionibacterium) acnes, Staphylococcus epidermidis, and Corynebacterium accolens, as commensals since they benefit from the nutrients on our skin but don’t seem to do much to us. However, C. acnes actually stimulate sebocytes to produce antimicrobial peptides, C. accolens produces a lipase that inhibits the growth of a common respiratory pathogen Streptococcus pneumonia, and S. epidermidis stimulates IL17A-producing CD8+ T cells that enhance wound healing. Therefore, recent work shows that these commensals microbes turn out to be mutualists.
However, bacteria that seem to be mutualists don’t always benefit the host. While S. epidermidis generally does, it is also a leading cause of death in premature infants and nosocomial infections. Conversely, we often think of Staphylococcus aureus as a professional pathogen due to diverse virulence factors and since it is one of the most frequent causes of skin and soft tissue infections, but >30% of healthy individuals are colonized asymptomatically by S. aureus, making it a commensal to these individuals.
Numerous examples of host-resident microbes blurring the boundaries between pathogens and mutualists led us to idea of contextual pathogenicity, which is the lens by which we discuss the examples in our review. Instead of “good bugs” and “bad bugs”, there is actually a continuum of pathogenicity and mutualism. Many factors, including the microbe’s genetics, interactions with other microbes, and host/environmental factors, determine the aggressiveness or mutualism of a microbe. We hope future work will aim to understand the mechanisms governing a microbe’s tendencies toward cooperation or aggression. This will help us understand the microbial rules governing human health and disease, and this could also allow us to engineer microbes to deliver therapeutics to specific, activated immune cell populations across an intact skin barrier.
This post was written with the help of Drs. Fischbach, Belkaid, and O’loughlin.