Assessing the effects of common topical exposures on skin bacteria associated with atopic dermatitis

Abstract

Background: While patients and families struggling with atopic dermatitis (AD) have documented concerns for a contributory role of skin care products in AD pathology, nearly all the skin microbiome studies to date have asked participants to avoid topical products (such as soaps or select medications) for the preceding days to weeks prior to sample collection. Thus, given the established role of the microbiome in AD, the interactions between topical exposures, dysbiosis and AD remains underrepresented in the academic literature. Objectives: To address this knowledge gap, we expanded our previous evaluations to test the toxicological effects of a broader range of common chemicals, AD treatment lotions, creams and ointments using both healthand AD-associated strains of Roseomonas mucosa and Staphylococcus spp. Methods: Use of in vitro culture techniques and mouse models were deployed to identify chemicals with dysbiotic or pre-biotic potential. A proof-of-concept study was subsequently performed in healthy volunteers to assess global microbiome shifts after exposure to select chemicals using dermatologic patch testing. Results: Numerous chemicals possessed antibiotic properties, including many not marketed as anti-microbials. Through targeted combination of potentially beneficial chemicals, we identified combinations which promoted the growth of health-associated isolates over disease-associated strains in bacterial culture and enhanced microbe-specific outcomes in an established mouse model of AD; the most promising of which was the combination of citral and colophonium (often sold as lemon myrtle oil and pine tar). Additional studies would likely further optimize the combination of ingredients use. Similar results were seen in the proof-of-concept human studies. Conclusions: Our results could offer a systematic, multiplex approach to identify which products carry dysbiotic potential and thus may guide formulation of new topicals to benefit patients with AD. | INTRODUCTIONAtopic dermatitis (AD) is an inflammatory disease of the skin associated with reduced quality of life and increased risk for developing asthma, allergic rhinitis and food allergies. 1 The microbiome is increasingly recognized as both a significant contributor to AD pathology 2 and a potential therapeutic target. [3][4][5][6] This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Exposure to isocyanates predicts atopic dermatitis prevalence and disrupts therapeutic pathways in commensal bacteria

“…Building upon prior open-label safety and activity of topical R. mucosa ( 8 , 9 ) a 15-site, placebo-controlled phase IIb trial in 154 patients aged 2 to 70 years was performed under a National Institutes of Health (NIH) license by Forte Biosciences Inc. ( Table 1 ). In the 2-week lead before enrollment, patients were provided a moisturizer regimen with minimal dysbiotic potential ( 16 ) and instructed to discontinue topical corticosteroids (TCS) throughout the study. Then, patients were treated three times per week for 4 months, followed by a 1-month washout in which both topical steroids and the preset moisturizers were withheld (fig.…”

“…Although not indicative of prescription approval, under a consideration of over-the-counter use, we tested an encapsulated probiotic form of Rm HV for stability (fig. S7D) and expanded our prior evaluation of products ( 16 ) into which Rm HV could be viably reconstituted (fig. S7E).…”

“…For our clinical results, failure to reach statistical significance during active treatment, in part, was due to overperformance of the placebo arm compared to a priori powering expectations. This overperformance may have been caused by the addition of a vehicle effect stemming from protocol requirements for twice-daily moisturization using a ceramide-containing regimen optimized to avoid inducing dysbiosis ( 16 ) combined with potential prebiotics effects of the sucrose in the placebo formulation.…”

“…S9E), PM2.5 ( 61 ), NO 2 (fig. S4A) ( 62 ), and dysbiotic skin care products ( 16 ). Given the reported benefit of air purifiers in AD ( 63 ), our experiments demonstrating partial reduction of TDI levels using a common air purifier (fig.…”

“…Our mechanistic evaluations demonstrated that the Rm HV improved outcomes via lipid mediators, which operate through potentiation of tumor necrosis factor receptor 2 (TNFR2) to induce established pathways of epithelial repair and inhibit the allergic mediators interleukin-13 (IL-13) and thymus and activation-regulated cytokine (TARC) ( 8 ). We further elucidated a potential direct role for topical skin care products in the development of AD-associated dysbiosis related to both Rm HV and commensal isolates of Staphylococcus ( 16 ).…”