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The Role of Skin Microbiome in Atopic Dermatitis
The skin microbiome is complex but is a key component of the pathogenesis in atopic dermatitis (AD).1 Research has shown that certain microbes are associated with AD and, therefore, may be the key to treatment.2 However, more research is needed to elu-idate the association between the skin microbiome and AD disease activity and heterogeneity.
To answer these questions, The Dermatologist reached out to Peter A. Lio, MD, who is a clinical assistant professor of dermatology and pediatrics at the Feinberg School of Medicine at Northwestern in Chicago, Illinois.
The Dermatologist: What is the importance of the skin microbiome in AD?
Dr Lio: We continue to learn about the tremendous importance of the skin microbiome in AD. During my training, it seemed the dominant mode of thinking was that Staphylococcus aureus was more of a colonizer and opportunist. However, and I trace it back largely to the landmark 2012 study by Kong and colleagues, this conceptualization has changed to favor the notion that S aureus very directly can cause flare ups and act as an independent disease driver.3
Now, a decade later, I think we have a deeper understanding that the microbiome is actually a functional part of the skin barrier and that if any aspect of the barrier becomes compromised, such as the chemical barrier, the physical barrier, or the immune barrier, then dysbiosis can occur. This imbalance then allows for S aureus (and perhaps other pathogens) to further advance inflammation and skin barrier damage.4
The Dermatologist: How does the skin microbiome change over the course of treatment?
Dr Lio: We now understand that even treatments that do not appear to directly affect the microbiome can have indirect effects on it. For example, we have seen that topical corticosteroids— known to have adverse effects on the skin barrier when used over time and are used to decrease the local immune response—paradoxically improve the microbiome! This seems strange at first but can be reconciled by the fact that when there is too much inflammation with subsequent barrier damage, decreasing the inflammation allows for balance to be regained. As a rule, I would argue, part of the definition of effective treatment is to see a normalization of the microbiome, so it really is fundamental.5,6
The Dermatologist: In what ways does severity of disease impact the skin microbiome?
Dr Lio: It seems that disease severity is associated with the degree of dysbiosis: the more severe the disease, the more abnormal the skin microbiome. However, we still have a lot to learn about this, and it probably is not truly universal. Some patients seem to be much more prone to dysbiosis, at least as far as we can tell clinically. Some patients, even on the milder side, can have many recurrent Staphylococcus skin infections, while others, some even very severe, seem less likely to develop these infections. That said, there are probably several factors that can influence this, including the genetic background of the patient, their particular microbiome composition, and environmental aspects. For example, I have had patients move to warmer climates like Florida and report back that the eczema had changed in character, sometimes actually getting worse. It is known that external factors such as humidity and temperature, as well as internal ones such as psychological stress, can affect the skin microbiome.
The Dermatologist: How does knowing more about the skin microbiome inform clinical practice and patient care?
Dr Lio: We are still in the early days of using this information to help patients. In fact, if anything, we have learned that some interventions that were thought to work via the microbiome actually may not directly affect it much at all. The “poster child” for this is perhaps dilute bleach baths. When the landmark paper was published in 2009, it was thought to be antibacterial against Staphylococcus.7 However, we now have a number of independent studies that convincingly suggest that dilute bleach baths, at least the way they are being used in AD, are not actually affecting the microbiome directly. However, that does not mean they do not work. Indeed, there is still a signal that they are helpful to some patients, and it may be via anti-inflammatory, anti-itch, or skin- barrier-repairing mechanisms.8 So, for now, I think that it means we continue to explore this space! From newer products that contain anti-staphylococcal enzymes (eg, endolysin), to treatments that appear to decrease the colonization of Staphylococcus on the skin, such as coconut oil.9 With lots of ongoing research, I am optimistic that we will have some exciting things to report in this space in the coming years!10
The Dermatologist: What future research is needed to better understand the skin microbiome in AD?
Dr Lio: I think we need to better understand the unique “signature” or “fingerprint” of an individual’s microbiome. We need to better understand how prebiotics (“food” that supports the growth of good bacteria), probiotics (viable organisms), and postbiotics could be harnessed both for the skin and for the gut.
What makes it very complex is that people are different, environments are different, personal routines are different, and there are seemingly infinite combinations of things that could potentially work. So, some of this may be a “big data” problem: it is possible that large and rapid screens of combinations of bacteria, perhaps along with machine learning, can help us better understand—and hopefully manipulate—this complex ecosystem on our skin.
1. Koh LF, Ong RY, Common JE. Skin microbiome of atopic dermatitis. Allergol Int. 2022;71(1):31-39. doi:10.1016/j.alit.2021.11.001
2. Khadka VD, Key FM, Romo-González C, et al. The skin microbiome of patients with atopic dermatitis normalizes gradually during treatment. Front Cell Infect Microbiol. 2021;11:720674. doi:10.3389/fcimb.2021.720674
3. Kong HH, Oh J, Deming C, et al. Temporal shifts in the skin microbiome associated with disease flares and treatment in children with atopic dermatitis. Genome Res. 2012;22(5):850-859. doi:10.1101/gr.131029.111
4. Strugar TL, Kuo A, Seité S, Lin M, Lio P. Connecting the dots: from skin barrier dysfunction to allergic sensitization, and the role of moisturizers in repairing the skin barrier. J Drugs Dermatol. 2019;18(6):581.
5. Olesen CM, Ingham AC, Thomsen SF, et al. Changes in skin and nasal microbiome and staphylococcal species following treatment of atopic dermatitis with dupilumab. Microorganisms. 2021;9(7):1487. doi:10.3390/microorganisms9071487
6. Gonzalez ME, Schaffer JV, Orlow SJ, et al. Cutaneous microbiome effects of fluticasone propionate cream and adjunctive bleach baths in childhood atopic dermatitis. J Am Acad Dermatol. 2016;75(3):481-493.e8. doi:10.1016/j.jaad.2016.04.066
7. Huang JT, Abrams M, Tlougan B, Rademaker A, Paller AS. Treatment of Staphylococcus aureus colonization in atopic dermatitis decreases disease severity. Pediatrics. 2009;123(5):e808-e814. doi:10.1542/peds.2008-2217
8. Sawada Y, Tong Y, Barangi M, et al. Dilute bleach baths used for treatment of atopic dermatitis are not antimicrobial in vitro. J Allergy Clin Immunol. 2019;143(5):1946- 1948. doi:10.1016/j.jaci.2019.01.009
9. Rustad AM, Nickles MA, Lio PA. Atopic dermatitis and Staphylococcus aureus: a complex relationship with therapeutic implications. J Dermatol Nurses’ Assoc. 2021;13(3):162-167. doi:10.1097/JDN.0000000000000619
10. Noor Bilimoria S, Lio P. Staphylococcus aureus and atopic dermatitis: unweaving a tangled web. Pract Dermatol. 2019;61-66.
