A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review

Dermatol Ther (Heidelb) (2020) 10:53–61 https://doi.org/10.1007/s13555-020-00352-4 REVIEW A Calm, Dispassionate Look at Skin Microbiota in Atopic Dermatitis: An Integrative Literature Review Pengjie Wan . Ji Chen Received: November 20, 2019 / Published online: January 20, 2020 Ó The Author(s) 2020 ABSTRACT Atopic dermatitis (AD) is a chronic common inflammatory skin disorder with clinical characteristics of pruritic, dry, and recurrent flares that involve the whole body. Recent studies have demonstrated that the skin microbiota, characterized by an overgrowth of Staphylococcus aureus (S. aureus), plays a critical role in the manifestation of AD. There is striking evidence that skin microbiota can modulate the development and progression of AD. Therefore, more and more therapeutic approaches are adopted for modifying skin microbiota. Here we discuss the role of skin microbiota in the etiology and maintenance of AD; furthermore, we summarize the effects of therapeutic treatments on skin microbiota in AD based on published literature. With the help of the theoretical guidance suggested by microbial metagenome analysis, the reconstitution of microbiota should be a promising way to harness the pathogens of AD and could be used as a brandnew therapeutic strategy in clinical trials. We believe that the targeted therapy of dysbiosis in Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.11494461. P. Wan
J. Chen (&) Department of Dermatology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China e-mail: AD may possibly become a unique approach to an integrated treatment program in the near future. Keywords: Atopic dermatitis; Skin microbiome; Skin microbiota; Staphylococcus aureus; Therapy Key Summary Points Skin microbiota is a complex ecosystem composed of bacteria, fungi, and viruses. Integrity of the diverse microbes plays essential role in maintaining homeostasis and preventing pathogens from invading skin. Recently, researchers found that increased colonization of Staphylococcus aureus (S. aureus) plays a critical role in the pathogenesis of atopic dermatitis (AD). In this review, we summarize the clinical features of imbalanced skin microbiota associated with AD, and we emphasize the effects of each therapeutic treatment and their influences on skin microbiota. Besides traditional treatment approaches, such as emollient, antibacterial treatment, tacrolimus, narrowband UVB, coal tar, biological therapy, and contact with nature, we also discuss novel treatments that are targeting specific strains of human microbiota. Intriguingly, the targeted therapy of dysbiosis in AD has the potential to become an integrated treatment in the near future. 54 INTRODUCTION Skin microbiota is a complex ecosystem composed of bacteria, fungi, and viruses. Balance and integrity of the diverse microbes play an essential role in preventing pathogens from invading skin [1], while the skin microbiome refers to the composition of all microbial genes in the skin’s community [2]. Atopic dermatitis (AD), a worldwide heterogeneous, recurrent, chronic pruritic disease due to epithelial barrier dysfunction, immune dysregulation, and skin inflammation with dysbiosis of skin microbiota and colonization by the predominant pathogen S. aureus, shows an increasing tendency [3, 4]. Many studies have found alterations in the composition of the microbiome in patients with AD compared with that of healthy individuals, and microbiota differs between lesional skin and non-lesional skin [5, 6]. AD can also affect the skin of any part of the body, but it generally shows age-related morphological and distributional characteristics [7]. With the development of new technology, the application of whole genome sequencing (WGS) allows access to all genes of virtually all inflammation with dysbiosis of skin microbiota. Next-generation sequencing (NGS) technology in clinical bacteriology has been interrogating thousands of 16S ribosomal RNA gene amplicons from bacteria to archaea in floras from a patient with AD [8, 9]. Currently, exploration of the skin microbiome in AD is attracting more and more attention from researchers. Dysbiosis in microbiota has been universally considered an important factor in the pathogenesis of AD, and how to achieve and maintain a balance between skin microbiota and the host has become a hot research topic in the field of AD treatment [10]. Although traditional treatments including topical glucocorticoid and calcineurin inhibitors can inhibit inflammation, the recurrence of AD continues. Focusing on microbiota therapy is currently being developed to revise skin dysbiosis related to AD, with the expectation of obtaining long-term remission. In this review, we give a brief introduction on clinical features of AD, then discuss the pathogenesis of skin microbiota in AD, and finally discuss the Dermatol Ther (Heidelb) (2020) 10:53–61 treatment strategies based on the skin microbiome by reviewing literature published till October 2019. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. CLINICAL FEATURES OF AD AND SKIN MICROBIOME The consistent increment in the prevalence of AD in both developing and developed countries has depicted a global trend in the burden of AD, and the picture in the developing world may soon resemble that in developed countries [11], where 15–20% of children have been affected [12, 13]. Nearly 70% of children with AD show disappearance of symptoms or spontaneous remission during puberty even in individuals with genetic heterogeneity of filaggrin mutations [14]. However, about 2–5% of adults worldwide can be affected and present as adultonset AD or infantile/childhood AD, and the dermatitis symptoms may persist or recur over many years [15, 16]. Newborns generally carry an adequately uniform microbiome. The microbial community composition of newborns is initially determined by the manner of delivery, i.e., newborns delivered naturally obtain bacteria in their mother’s vagina that are dominated by Lactobacillus, while those born by Caesarean section should inherit microbiota resembling those on their mothers’ skin [17]. Although the skin lesions of infants are rather diffuse, it should be noted that most of the lesions occur on their faces and extensor sides of extremities [18]. Skin lesions on adults vary from a small localized plaque to a widespread lichenification, and even erythroderma. Shi et al. in 2016 identified that the skin microbiome of AD was significantly different between young children and adults–teenagers [14]. The skin microbiome during AD flares was investigated at species level by Byrd et al. [9]; dynamics of the microbial community from the pediatric AD group was consecutively monitored throughout the course of the disease. Eventu (...truncated)