The Microbiome and Atopic Dermatitis

Heidi H. Kong, MD, MHSc, head of the cutaneous microbiome and inflammation section, dermatology branch, NIAMS/NIH.

Researchers have been aware that patients with atopic dermatitis (AD) have unique bacterial footprints, both in their gastrointestinal tracts and on their skin, for decades. Recently, however, an explosion of scientific interest in the collective assortment of microorganisms that live throughout the body, known as the human microbiome, has shed more light on the role those bacteria may play in the development, and eventually, management, of AD.  

The Dermatologist spoke with Heidi H. Kong, MD, MHSc, a board-certified dermatologist and head of the cutaneous microbiome and inflammation section at the National Institute of Arthritis and Musculoskeletal and Skin Diseases/National Institutes of Health (NIAMS/NIH), about what is currently known about this complex relationship. 

Q. The microbiome refers to every living organism collectively throughout the body. Is what happens on skin or in skin different from what happens elsewhere?  

A. The Human Microbiome Project¹ looked at five different sites: nares, oral cavity, skin, gastrointestinal tract, and vaginal mucosa. We found that the microbial communities in those areas differed from each other. We also showed that the skin microbial communities can vary from person to person. There are some commonalities, likely based on skin physiology. Foreheads tend to have much more Cutibacterium acnes, for example, because we have many more oil glands on our foreheads, and creases and folds like armpits may have more Corynebacterium bacteria because there is more sweat in those areas. In fact, your forehead and my forehead swabs are more likely to be similar to each other than my forehead to my own arm or foot. 

Q. Can you discuss how you used genomics to examine some of these microbes in patients with AD? 

A. If there are difficult-to-culture bacteria, for example, then sequencing would be able to help us identify that bacteria more easily than culture-based studies. Our research showed that Staphylococcus aureus and Staphylococcus epidermidis is increased in the skin of children who have flares of their skin disease.² We also showed that there were particular strains of S aureus that appeared to increase in certain patients.

Q. Do you have any theories about what distinguished the patients who did show an increase in those bacteria from those who did not?

A. In our small cohort, patients who had more severe AD tended to have primarily one particular strain that increased significantly during their flares.² We didn’t see this as much in children who had less severe AD flares. Interestingly, the strains of S aureus were different for each of the patients we studied, likely suggesting that there is a component of the host involved. That involvement could potentially be related to the host’s immune system, genetics, skin barrier, or a combination of all those different factors playing a role in shaping which strains are on their skin and which ones may bloom during flares. 

Q. You were focusing primarily on children in your studies. Do you have enough data to say whether you feel the same would be true in adults? 

A. That is complicated. There are conflicting views on whether adults who have severe eczema are classically defined as having AD. Altered skin flora has been reported in adult patients, so there may be altered host-microbial crosstalk in adults too. 

Q. Your research indicates a definite difference between chronic and mild forms of the disease. Do you have any theories as to why AD might affect some people more significantly, and whether bacteria play a role in that? 

A. I don’t think we know why some people have more severe disease than others. At the NIH Clinical Center, there are many investigators who have cohorts of patients with primary immunodeficiency who also have eczematous dermatitis. These patient cohorts provide us a way of trying to tease that apart. 

We know in these primary immunodeficiency syndromes, particularly, some have defined genetic mutations, and then they have severe skin disease, severe eczema. Last year, for example, we published on a cohort of patients with DOCK-8 deficiency.³ These patients with DOCK-8 deficiency can have extremely severe eczema. In their microbiomes, we found that viruses were much higher, and predominated over bacteria and fungi. That suggests that it is not necessarily all just environment, but something about the host helping to define or shape what microbes are present on the skin.

Q. What other factors have you found may play a role? 

A. There have been studies where different types of S aureus have been cultured and examined. In one study with mice, we showed that some strains of S aureus did not result in the same type of skin thickening and inflammation that we saw with the strains that we’ve collected from our patients with severe AD, suggesting that there are bacterial strain differences.² That demonstrates the importance of studying the strains of the bacteria (or whatever microbes you’re examining) on patients, and not completely relying on lab strains. Different strains may have different biological activity.

There has also been lab work showing that the host immune response to the same bacteria differs depending on when exposure occurred, during the neonatal period vs adult period.⁴ So even the timing of when a host organism becomes exposed to microbes may be important.

Q. What is understood about the microbiome’s relationship to immunity? 

A. Early on, studies pointed to the importance of microbes to the host’s immune system. They used what were known as “germ-free mice,” which were delivered sterilely by C section and raised in a germ-free environment. In those mice, organs do not develop completely and their immune systems do not function normally. That suggests that microbes are important in immune system development. Then you have research with these immunodeficient patients showing the importance of the immune system in shaping what microbes can be present on a person’s skin.³ There is this bidirectional communication between microbes and host immunity that likely keeps both those things in check.

Q. What do you feel is the next step in terms of research? 

A. We still need more evidence that the specific bacterial strains do influence skin disease. Other epidemiologic research suggests that certain exposures to environments as well as the microbiota in those environments may help or may contribute to the development of the disease—factors such as rural vs urban environments, the number of siblings an individual has, or exposures to, say, farms or pets. In that case, it would be important to see if certain microbes in the environment indeed affect the development of a disease like AD. There isn’t sufficient research yet, nor sufficient data to know these answers.

Q. How could this kind of research ultimately impact the way we treat AD?

A. That is an incredibly complicated question because the data that has been published suggests that AD is multifactorial, where the host factors such as genetics, birth mode, and even home family environment all potentially contribute to the disease. Early studies have described that topical application of some bacteria (eg, Staphylococcus hominis or Roseomonas mucosa) may reduce severity of AD; more studies are needed.^5,6 

Having one treatment likely will not help everybody’s AD. Understanding more about the phenotypes or the subgroups of AD may be helpful in trying to find which types of patients may respond better to a particular treatment. Because there is so much heterogeneity within a disease like AD, a single approach may not be enough. It may be frustrating that we can’t point to one thing and say, “This definitely will help all patients,” but we are continuing to develop ways to better understand how the microbiome potentially influences diseases like AD. 

References

1. Human Microbiome Project. National Institutes of Health website. https://hmpdacc.org. Accessed June 25, 2019.

2. Byrd AL, Deming C, Cassidy SKB, et al. Staphylococcus aureus and Staphylococcus epidermidis strain diversity underlying pediatric atopic dermatitis. Sci Transl Med. 2017;137(3):561-568. doi.org/10.1016/j.jid.2016.10.033

3. Tirosh O, Conlan S, Deming C, et al. Expanded skin virome in DOCK8-deficient patients.  Nat Med. 2018;24(12):1815-1818. doi:10.1038/s41591-018-0211-7

4. Scharschmidt TC, Vasquez KS, Truong HA, et al. A wave of regulatory T cells into neonatal skin mediates tolerance to commensal microbes. Immunity. 2015;43(5):1011-1021. doi:10.1016/j.immuni.2015.10.016

5. Paller AS, Kong HH, Seed P, Naik S, et al. The microbiome in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(1):26-35. doi.org/10.1016/j.jaci.2018.11.015

6. Nakatsuji T, Chen TH, Narala S, et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med. 2017;9(378). doi:10.1126/scitranslmed.aah4680