Atopic Dermatitis and the Role of the Skin Microbiome in Choosing Prevention, Treatment, and Maintenance Options

October 2020 | Volume 19 | Issue 10 | Original Article | 935 | Copyright © October 2020


Published online October 2, 2020

Hilary Baldwin MDa, Crystal Aguh MDb, Anneke Andriessen PhDc, Latanya Benjamin MD FAAP FAADd, Aaron S. Ferberg MDe, Deirdre Hooper MD FAADf, Joseph L. Jarizzo MDg, Peter A. Lio MDh, Brook Tlougan MD FAADI, Heather C. Woolery-Lloyd MDj, Joshua Zeichner MD FAADk

aAcne Treatment and Research Center, Brooklyn, NY bEthnic Skin Program, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD cRadboud University Medical Center, Nijmegen, The Netherlands; Andriessen Consultants, Malden, The Netherlands dFlorida Atlantic University, Boca Raton, FL eArkansas Dermatology Skin Cancer Center, Arkansas Research Trials, Little Rock, AR; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY fAudubon Dermatology; Tulane and Louisiana State Universities, New Orleans, LA gWake Forest School of Medicine and Weill Cornell Medical College, Winston Salem, NC, and New York, NY hDepartment of Dermatology, Feinberg School of Medicine, Northwestern University; Medical Dermatology Associates of Chicago, Chicago, IL iWestmed Medical Group, Purchase, NY; Columbia University Irving Medical Center, Manhattan, New York, NY jFrost Department of Dermatology and Cutaneous Surgery, Miller University of Miami School of Medicine, Miami, FL kDepartment of Dermatology, Mount Sinai Hospital, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY

does not completely address all aspects of the flawed physiology of the cutaneous barrier. Furthermore, the durability of effect is relatively short lived. As such, they offer only partial and temporary restoration of the skin’s barrier function.36 Utilizing barrier repair creams with physiologic lipids help to address the shortcomings of conventional everyday moisturizers.

Restoring the Diversity of Skin Microbiota in AD Patients
Skin microbes play a critical role in maintaining skin health (eg, suppressing pathogenic species, priming the immune system, preventing inflammation and infection). Microorganisms require water to thrive, and the amount of available water in particular areas partially determines which type of bacteria can inhabit that location. In such a way, water can be viewed as both a culture medium and a prebiotic.41 Dry environments favor the growth of S. aureus and inhibit the growth of beneficial commensal organisms such as coagulasenegative staphylococci.29 Commensal bacteria thus compete with pathogenic bacteria for the same ecological niche. In unfavorable environmental conditions, (ie, dry skin), this can become problematic as commensal bacterial are an integral part of the healthy innate immune system and provide protection against inflammation and infection.29 Therefore, maintaining the skin’s moist barrier and homeostatic microbiota is necessary to reduce the promotion of pathogenic species and the chronic persistence of AD symptoms.

Through overpopulation of pathogenic organisms comes a loss of the skin's barrier and, subsequently, increased susceptibility to chronic inflammation. This understanding of the critical role of the cutaneous barrier in the pathogenesis of AD has led to recent advances in barrier repair therapies. Many topical treatments have been found to restore the skin's barrier in AD36,42,43 and some have been found to diversify bacteria preceding the observed improvements in skin barrier function and disease severity.34 This has led to the hypothesis that the regulation of bacterial populations is necessary to restore skin homeostasis in AD. While emollients can restore barrier function, experts agreed that this is not sufficient to treat ADaffected skin. Instead, they proposed that regulation of bacterial populations to restore homeostasis is required.

The effect of supplementation with probiotics on AD development and severity has been studied in various clinical trials with controversial results.44-48 Some studies have evaluated the application of prebiotics to "feed" the bacteria, which are part of the healthy epidermis. Following promising preclinical results,49,50 a treatment formula containing lysates from the Gram-negative bacterium Vitreoscilla filiformis, grown in a LRPThermal Spring Water (TSW), significantly improved AD severity in a randomized trial.51

Post-biotic Aqua Posae Filiformis
The post-biotic Aqua Posae Filiformis (APF), a biomass of Vitreoscilla filiformis, a non pathogenic bacteria grown in a medium containing La Roche Posay Themal spring water (LRPTSW) has been shown to act on the balance of the microfloral balance, without the use of antibiotics.50 LRP-TSW exhibits both pre- and probiotic properties that enhance the diversity of the skin microbiome.52 A recent review was undertaken to explore the role of LRP-TSW as a topical pre- and probiotic therapy in improving the diversity of the skin microbiota and reducing dryness and pruritus in inflammatory skin diseases.52 Investigators concluded that the concentration of minerals (eg, selenium) and nonpathogenic microbes in crude LRP-TSW is thought to explain its therapeutic benefit when used for inflammatory skin diseases at the thermal center of LRP. Clinical studies have shown topical LRP-TSW treatments stimulate the growth of Gram-negative bacteria at the expense of Grampositive bacteria, which improves skin microbial diversity.52 This results in an improvement in both non-diseased dry skin and inflammatory skin conditions. These findings support the historical use of thermal spa waters to treat inflammatory disorders. LRP balneotherapy has been shown to effectively treat AD through optimizing microbial diversity to decrease the severity of active lesions.52

Recently, it was found that applying an emollient containing LRP-TSW and the biomass of APF (Lipikar Balm AP+, La Roche- Posay Pharmaceutical Laboratories, France), to AD-affected skin was able to return the compositional balance of the microbiome to that of nearby unaffected skin. The composition of this LRPTSW and APF emollient has been described previously and is summarized in Table 1.54 In this pivotal study, AD symptoms improved for over 70% of the subjects, with a concurrent increase of bacterial diversity and a decrease in the abundance of Staphylococcus on the affected skin.54 This trial was significant for confirming the importance of a reduction in the composition of microbial communities in AD flares. For the first time, investigators demonstrated that the topical application of a prebiotic could be used as a therapeutic approach to modulate or balance the immune system and normalize the cutaneous microbiota. Moreover, these results were found to last for at least one month following the discontinuation of the treatment.55

DISCUSSION AND CONSENSUS

Guidelines for the topical treatment of AD have not changed significantly over the past ten years with the exception of the introduction of crisaborole.4,8,34,36 However, treatment of more severe AD has changed dramatically due to the development of agents that target immune responses and inhibit T cells and target Th1, Th2, Th22, phosphodiesterase-4 (PDE4), IL-4, and IL- 31.56 The traditional paradigm of using steroid and antimicrobial strategies to control AD flares is shifting towards a more holistic approach, which encourages optimizing the microbiome through regulatory factors.30-32 Advisors agreed that the skin microbiota plays a key role in dermatologic health and disease and that skin barrier repair is imperative to AD management.2,3,21,23 As such,