Microbiome-containing Moisturizers in Atopic Dermatitis: Hope or Hype

Madam, Skin is composed of a variety of niches selecting for colonization by specific microorganisms. The common cutaneous bacterial commensals are Staphylococcus epidermidis, Propionibacterium acnes, and Corynebacterium in wet areas sebaceous follicles, Actinobacteria, Proteobacteria, Firmicutes, and Bacteriodetes in dry areas (forearm, buttock, and hand) and fungal skin commensals are Malassezia, Rhodotorula, Debaromyces, Cryptococcus, and Candida. The microbiome is defined as the sum of microbes, their genomes, and interactions in a given ecological niche.[1] Host factors, for example, sex, age, and environmental exposures, also affect the niches and microbiome communities. The alteration of the skin and microbial composition is called dysbiosis. A recent review defined the bidirectional relationship between dysbiosis and skin barrier dysfunction. Hence, dysbiosis leads to barrier dysfunction, and barrier dysfunction results in aberrant microbiome.[1] Glimpse of Atopic Dermatitis It is a common chronic pruritic inflammatory skin disorder. Atopy is defined as an inherited tendency to produce immunoglobulin E antibodies in response to minute amounts of common environmental proteins such as pollen, house dust mites, and food allergens. The disorder exhibits periods of exacerbation and remission. Genetic (filaggrin gene mutation), immune (Th2 differentiation of naive CD4+ T-cells), and environmental factors (hygiene hypothesis) interact in a complex fashion to contribute to disease expression. Currently, it is widely accepted that a defective skin epidermal barrier results in increased transepidermal water loss as well as increased colonization and penetration by microorganisms and allergens, evoking inflammatory responses. Atopic dermatitis (AD) commonly presents in infancy (early onset) or childhood (20%) but can also occur in adults (late onset). Clinically, AD presents as xerotic, erythematous, scaly skin, and early onset of pruritic lesions localized at typical sites (face and extensors in infants and flexures of elbows, knees, wrist, and ankles in children and adults) [Figures 1 and 2].Figure 1: Erythematous, scaly and itchy lesions around both eyes along with Dennie Morghan folds in a childFigure 2: Hyperpigmented to erythematous itchy lesions over both popliteal fossa of childRole of Microorganism in Pathogenesis of Atopic Dermatitis As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for the function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. S. aureus species grow poorly in acidic conditions, as seen in healthy stratum corneum, but grow much better in higher pH conditions, which are often seen in patients with AD.[1]S. aureus α-toxin is a cytotoxin critical to the formation of the S. aureus biofilm. Flares of the disease are associated with an expansion of S. aureus on lesional skin and a substantial loss of biodiversity in skin microbiome. In contrast to healthy skin, AD skin is permissive for S. aureus colonization. The antimicrobial peptides LL-37, β-defensins, and dermcidin are present at reduced levels in AD skin. One mechanism underlying this effect is the known inhibition of interleukin (IL)-4 and IL-13 on human β-defensin 2 and 3 gene expression.[2] It has been assumed that small intestine permeability may be increased in AD patients. Intestinal permeability is one factor in acquired food allergy. Intestinal microbiome is dynamic during the first 3 years of life before stabilizing. In contrast to skin microbiome, intestinal microbiome demonstrates heritability.[3] Disturbances in intestinal microbiome could be a risk factor for further AD development.[3] Potential Role of Biotherapy for the Treatment of Atopic Dermatitis The current methods of surface microbial restoration come in four general forms: prebiotics, probiotics, parabiotics, and postbiotics. Probiotics are the viable commensal microorganisms. Prebiotics are food components that promote commensal bacterial growth but are not digested by humans. Synbiotics refer to a combination of probiotics and prebiotics, delivering both the organism and its substrate for growth. Postbiotics and parabiotics are both nonviable. Postbiotics are the chemical byproducts of bacteria that are either secreted by live bacteria or released following bacterial lysis. Conversely, parabiotics are intact but inactivated probiotic cells. Microbiome-containing Moisturizers in Atopic Dermatitis Moisturizers help in barrier repair and reduce transepidermal water loss. Hence, moisturizers are an important and inexpensive prevention and treatment tactic. Guidelines recommend liberal application of moisturizer on lesional and nonlesional skin, ideally at least twice daily in AD patients.[4] The shift from traditional moisturizers to those with bioactive ingredients, anti-inflammatory agents, and microbiome-modulating effects opens a realm of possible therapeutic options.[5] Not all moisturizers are beneficial, some negatively impact skin function, and in doing so, they risk inducing or exacerbating inflammation in patients with AD.[5] The evidence exists to suggest that gastrointestinal probiotics and prebiotics may offer benefit in preventing and reducing the severity of AD. Specifically, Lactobacillus rhamnosus was effective in the long-term prevention of AD development. γ-Linolenic acid reduced the severity of AD. Supplementation with prebiotics and blackcurrant seed oil (γ-linolenic acid and ω-3 combination) was effective in reducing the development of AD.[6] Low diversity in the gut microbiota during early infancy has been associated with the development of atopic eczema later in life. The manipulation of gut microbiota through probiotics, prebiotics, or microbiota transplant has a great potential in the treatment and/or prevention of skin diseases such as AD.[7] A new concept of the pathogenesis of AD has emerged, which considers the microbiome, barrier function, and AD as an interplaying trinity. Many topical treatments have been found to restore the skin barrier in AD and some have been found to diversify bacteria preceding the observed improvements in skin barrier function and disease severity. This has led to the hypothesis that the regulation of bacterial populations is necessary to restore skin homeostasis in AD.[8] While emollients can restore barrier function, this is not sufficient to treat AD-affected skin. Instead, 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.[9] Following promising preclinical results, a treatment formula containing lysates from the Gram-negative bacterium Vitreoscilla filiformis, grown in a La Roche Posay (LRP) thermal spring water (TSW), significantly improved AD severity in a randomized trial.[10] The postbiotic Aqua Posae Filiformis, a biomass of Vitreoscilla filiformis, a nonpathogenic bacteria grown in a medium containing LRPTSW has been shown to act on the balance of the microfloral balance, without the use of antibiotics. LRP balneotherapy has been shown to effectively treat AD through optimizing microbial diversity to decrease the severity of active lesions.[11] Conclusion A working group of clinicians, all experienced in managing patient populations with AD, convened for a 1-day meeting in New York City on November 2, 2019. To optimize clinical outcomes in AD, the panel reviewed literature surrounding the topic of the skin microbiome in patients with AD and developed and discussed clinical recommendations related to the prevention, treatment, and maintenance of AD. Guidelines for the topical treatment of AD have not changed significantly over the past 10 years with the exception of the introduction of crisaborole. The common consensus in various reviews and clinical trials concludes that skin microbiota plays a key role in dermatologic health and disease and skin barrier repair is imperative to AD management. Overall, experts agreed that maintaining microbial homeostasis is a crucial component of AD therapies.[12] Currently, AD management program that includes reduction of pathogenic organisms, optimizing the re-population of the healthy diversified microbiome, and restoring the skin barrier. As the microbiome plays a role in the prevention of AD and also in the active phase of the disease, a product displaying pre- and postbiotic activity may prove beneficial although more data are required to reach the conclusion whether it is hope or hype. Declaration of consent The authors certify that they have obtained all appropriate consent forms, duly signed by the parent(s)/guardian(s) of the patient. In the form, the parent(s)/guardian(s) has/have given his/her/their consent for the images and other clinical information of their child to be reported in the journal. The parents understand that the names and initials of their child/children will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.