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      Microbiome of the Skin and Gut in Atopic Dermatitis (AD): Understanding the Pathophysiology and Finding Novel Management Strategies

      review-article
      1 , 2 , 3 , *
      Journal of Clinical Medicine
      MDPI
      atopic dermatitis, microbiota, microbiome, skin, gut, therapeutic implications

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          Abstract

          Atopic dermatitis (AD) is a long-standing inflammatory skin disease that is highly prevalent worldwide. Multiple factors contribute to AD, with genetics as well as the environment affecting disease development. Although AD shows signs of skin barrier defect and immunological deviation, the mechanism underlying AD is not well understood, and AD treatment is often very difficult. There is substantial data that AD patients have a disturbed microbial composition and lack microbial diversity in their skin and gut compared to controls, which contributes to disease onset and atopic march. It is not clear whether microbial change in AD is an outcome of barrier defect or the cause of barrier dysfunction and inflammation. However, a cross-talk between commensals and the immune system is now noticed, and their alteration is believed to affect the maturation of innate and adaptive immunity during early life. The novel concept of modifying skin and gut microbiome by applying moisturizers that contain nonpathogenic biomass or probiotic supplementation during early years may be a preventive and therapeutic option in high risk groups, but currently lacks evidence. This review discusses the nature of the skin and gut flora in AD, possible mechanisms of skin–gut interaction, and the therapeutic implications of microbiome correction in AD.

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          Most cited references123

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          Interactions between commensal intestinal bacteria and the immune system.

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            The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch.

            Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin that affects one in ten people. Patients suffering from severe AD eventually progress to develop asthma and allergic rhinitis, in a process known as the "atopic march." Signaling between epithelial cells and innate immune cells via the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the atopic march. Here, we report that epithelial cells directly communicate to cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT calcium signaling pathway as an essential regulator of TSLP release from keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors. Our results support a model whereby calcium-dependent TSLP release by keratinocytes activates both primary afferent neurons and immune cells to promote inflammatory responses in the skin and airways. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Low diversity of the gut microbiota in infants with atopic eczema.

              It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P = .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P = .02 and P = .01) and the phylum Proteobacteria at 12 months of age (P = .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R [edgeR] test: P = .008, q = 0.02). Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                02 April 2019
                April 2019
                : 8
                : 4
                : 444
                Affiliations
                [1 ]Department of Dermatology, St. Paul’s Hospital, The Catholic University of Korea, Seoul 06591, Korea; mdkjeun@ 123456naver.com
                [2 ]Department of Dermatology, Incheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
                [3 ]Department of Biomedicine & Health Sciences, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea
                Author notes
                [* ]Correspondence: hazelkimhoho@ 123456gmail.com ; Tel.: +82-32-280-5105
                Author information
                https://orcid.org/0000-0003-1670-0995
                https://orcid.org/0000-0003-0576-0474
                Article
                jcm-08-00444
                10.3390/jcm8040444
                6518061
                30987008
                98c78719-d4b8-45da-91ee-db1f314670f1
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 February 2019
                : 28 March 2019
                Categories
                Review

                atopic dermatitis,microbiota,microbiome,skin,gut,therapeutic implications

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