Updates in AD: Overview of Skin Microbiome

In this episode, Nathan Bowers, MD, reviews the role of the skin microbiome in atopic dermatitis and therapeutic options that target this aspect of the disease.

Dr Bowers is a resident with the department of dermatology at Wake Forest School of Medicine in Winston-Salem, NC.

Transcript

Melissa: Hello, everyone. In this episode of “Updates in Atopic Dermatitis,” I’ll be speaking with Dr Bowers, resident at Wake Forest School of Medicine in Winston-Salem, North Carolina about the role of the skin microbiome in atopic dermatitis. Thank you for joining us again today, Dr Bowers.

Dr Nathan Bowers: Thank you for having me.

Melissa: What is known about the role of the skin microbiome in the development and severity of atopic dermatitis?

Dr Bowers: Recent evidence suggests, or strongly supports, the concept that the skin immune system works together with specific microbes within the skin microbiome to protect against overgrowth of opportunistic pathogens.

Environmental factors, including pH, temperature, skin dryness, host genetics, antibiotic use, and hygiene practices actually play a critical role in the maintenance and stability of our microbiome. Dysregulation of these systems can disrupt the structure of the microbial community, a condition that is dysbiosis, which often reflects dominance by one microbe and a decrease in the richness and diversity of microbes.

In many cases, this can actually trigger the disruption of skin homeostasis and the development of disease. This phenomenon is well-characterized in atopic dermatitis. In particular, subjects with atopic dermatitis are highly colonized by Staph aureus and show a loss of bacterial diversity of the skin.

Staph aureus exhibits skin or causes skin inflammation and exacerbates it through really multiple mechanisms, including diverting both the adaptive and innate immune response, the release of bacterial toxins, and the disruption of proteolytic balance within the skin, which can contribute to barrier dysfunction. Collectively, these mechanisms have been demonstrated to contribute to exacerbations and severity of atopic disease.

Actually, interestingly, there’s been a recent study that showed that colonization by Staph aureus strains isolated from patients with severe atopic dermatitis elicits more inflammation in mouse skin than that by strains isolated in patients with less severe atopic dermatitis suggesting that the capacity of Staph aureus to exacerbate atopic dermatitis may actually be strain-dependent and specific.

Melissa: Could you elaborate more on how addressing the skin microbiome is thought to improve AD?

Dr Bowers: Yeah, absolutely. There’s a lot we can talk about, but I’m going to focus in particular on the role of Staph aureus by highlighting just a couple studies that demonstrate that, by decreasing the abundance of over-colonization with Staph aureus in the skin, this can correlate with improvement of skin inflammation.

Kobayashi published a paper in 2015 in Cell’s journal Immunity demonstrating that, in a mouse model, dysbiosis drives atopic dermatitis, and that decreasing Staph aureus burden can improve disease in their model.

In another article, that was by Julie Segre’s lab, demonstrated that in children with atopic dermatitis the proportion of Staph bacterial sequences, particularly Staph aureus, was greater during disease flares than at baseline or post-treatment and correlated with worsening disease severity.

Another interesting study that came out recently was by Colin, et al, demonstrating the treatment-associated changes in skin bacterial diversity, suggesting that atopic dermatitis treatments diversify skin bacteria. Interestingly, in this study, they noted that this diversification of bacteria actually precedes improvement in disease activity.

Collectively, these studies suggest that addressing dysbiosis in atopic dermatitis – in particular, Staph aureus over-colonization – and restoring bacterial diversity is important when we think about how addressing the microbiome of the skin can improve atopic dermatitis.

Melissa: To date, which therapeutic options that target the skin microbiome or being developed or studied, and what is the efficacy of these options?

Dr Bowers: Yeah, great question. There’s really existing and emerging therapeutics in atopic dermatitis that are targeted toward the inflammatory response of active disease that can actually have an effect on skin microbiomes.

Established therapies have already been shown to influence the skin microbiota and improve disease outcomes. Specifically, in atopic dermatitis, the use of narrow-band ultraviolet-B therapy has been shown to significantly reduce the concentration of Staph aureus and decrease superantigen production through an effect on pro-inflammatory peptides.

When we think about more recent data in this area, there’s been studies in atopic dermatitis that have focused on the clinical utility of modulating the microbiota. There was a paper by Nakayetsu. They looked at treating five patients with strains of Staph epidermidis and Staph hominis with antimicrobial properties against Staph aureus.

These strains were formulated into a vehicle and applied topically to lesions, and they actually saw a significant decrease in the abundance of Staph aureus at the application site.

This group, Miles, et al, showed that the topical transplantation of a specific bacteria, Roseomonas mucosa, in 10 adults with no preexisting gram-negative bacilli was associated with a clinical improvement in both adult and pediatric patients with atopic dermatitis.

These preliminary studies really provide a basis and rationale for the development of bacterial therapy, or therapies specifically targeted at the microbiome. There’s actually a couple topical medications in trial right now.

There’s one looking at a specific bacteriolysin that targets Staph aureus, and then there’s another that looks at allogeneic targeted microbiome transplants in patients with atopic dermatitis. We’re still waiting to see some of the data in those areas.

Melissa: In addition, what other research is needed for improving the understanding of the skin microbiome and developing those treatment options?

Dr Bowers: With next generation sequencing, that’s really allowed for the detection and characterization of numerous components of the cutaneous microbiome. However, ongoing research focused on understanding how these complex communities function is still in its early stage.

Although we’ve learned a lot, there are still questions around how the microbiome affects skin immunity, how that interaction plays a role on the initiation of atopic disease, the exacerbation of disease, and the role it plays in the chronicity of atopic dermatitis.

As we learn more about the function of the cutaneous microbiome, it’s become clear that these complex do play a fundamental role in the inflammatory skin disease we see in atopic dermatitis.

Melissa: Do you have any final thoughts or key takeaways you would like to leave the audience?

Dr Bowers: Yeah, I think in this area in particular, it’s interesting to think that in the not-so-distant future, there may be a change in dermatology clinical practice with the advent of new treatment paradigms reliant on an appreciation of the role of the cutaneous microbiome in chronic conditions.

This could change the way patients presenting with common skin conditions, such as atopic dermatitis, are managed. Things like bacterial therapy, improved probiotics and prebiotics, and perhaps even skin microbiota transplants could one day be incorporated into our treatment arsenal for atopic dermatitis, which is really an interesting thing to think about.

Melissa: Thank you so much.

Dr Bowers: No, thank you for having me.