RESEARCH FROM LABS AROUND THE WOLD

The ‘microbiome’ is a trending concept these days – and just as the gut hosts a large population of beneficial microbes, so, too, there is a normal skin microbiome. Of course, it has been known for decades that our outer skin layer, the stratum corneum, supports the residence of certain species of bacteria, its so-called ‘normal flora’.

These normal commensals provide skin with a host of benefits. The most important of these is their ability to successfully out compete – at least most of the time – certain species of ‘bad bugs’, like Staph. aureus.

In essence the good bacteria on our skin keep the bad ones from taking up residence and causing problems.

But only a minority of the bugs that inhabit our skin could be identified by the culture methods that were the only means available to the scientists of yore. The recent revolution in microbial genetics has circumvented this need to grow out a microbial species in order to identify it. Using these new, DNA-based techniques, a vast array of additional microbes that also inhabit our skin have been identified – literally myriads of species that had gone undetected in the past.

Just as a whole host of organisms form the gut microbiome, the skin too possesses a vast microbiome. In fact, the sheer burden of these organisms is mind-boggling – it turns out that we are only about 43% human, with much of the rest of us consisting of microorganisms – an average of 39 trillion bugs in all! While we humans only possess about 20,000 genes, our resident microbes, in the gut, skin and elsewhere, display from 2 to 20 million genes!

It is now clear that the microbiome of the skin and the gut are very different – not only in their profile of species but also in their ecology.

In a plenary lecture that kicked off the recent 2018 IID meeting in Orlando, Rob Knight, Ph.D., from the Department of Pediatrics at the University of California San Diego, described how the total burden and diversity of organisms that reside on our skin differ greatly from individual to individual, and also totally differ from the organisms that inhabit the gut. The skin’s microbiome can also change within a day or two, and is influenced greatly by our lifestyles, including where we live.

For example, in rural areas, we pick up a lot of organisms from the soil, to form a kind of Earth-Soil-Skin biosystem.

Changes in external temperature and humidity also alter the skin microbiome, explaining, for example, the differences in the bugs that inhabit our moist body folds, such as our arm pits or groins, vs. the rest of our skin. And of course, oral antibiotics can drastically alter the microbiomes of both the skin and the gut, with still uncertain consequences for our health.

Returning to the gut, Knight then described how the gut microbiome is now implicated in a host of diseases, including obesity, inflammatory bowel diseases, and, increasingly, with disorders of the nervous system, like autism. It is now envisioned that vaccines, prepared from the gut microbiome, could be used to treat or prevent obesity, anxiety disorders, and even the consequences of excessive stress.

Few scientists know more about the skin’s microbiome than Richard L. Gallo, Chairman of the Department of Dermatology at the University of California San Diego. Gallo has discovered certain strains of Staphyloccos aureus in the normal skin flora (another term for our microbiome) that are not bad actors like the rest of their family. Instead, these good strains of Staph. produce antimicrobial peptides, which can fend off the bad bugs – most importantly, they inhibit growth of those bad kinds of Staph. aureus, which can trigger recurrent episodes of atopic dermatitis.

One cardinal feature of atopic dermatitis is that it is deficient in a key antimicrobial peptide, which may explain why the disease is often flares when the skin becomes colonized by harmful strains of Staph.

At the recent IID meeting, Gallo described initial studies with topical applications of a ‘soup’ prepared from organisms that had been isolated from the skin of patients with atopic dermatitis while their disease was in remission. First in mice, and then in a small group of patients with atopic dermatitis, his group showed that this soup, which he terms ‘extended biotherapy’, displaces the bad bugs, and improves the inflammatory component of the disease.

Also of importance is that this form of therapy appears to be safe – no side effects were observed in the 41 patients who participated in this study. This raises hope that this form of therapy could be safely used in infants and young children. Because our prior studies have shown that the permeability and antimicrobial barriers are intimately linked (i.e., change one function for the better or worse, and the other will change in parallel), we suspect that this microbial soup will also improve barrier function in patients with atopic dermatitis – a possibility that we hope Dr. Gallo and his coworkers will explore in their future studies.

As a result of these favorable initial studies, larger trials already are underway at both UCSD and National Jewish Medical Center in Denver. Indeed, a ‘biosoup’ for the topical therapy of atopic dermatitis is presently under development by MatrySis Bioscience. Stay tuned for further developments on this promising front!