Citation: Rinaldi, F.; Trink, A.; Papale, A.; Giuliani, G.; Pinto, D. Clinical Translation of Microbiome Research in Alopecia Areata: A New Perspective? Cosmetics 2022, 9, 55. https://doi.org/10.3390/ cosmetics9030055 Academic Editor: Enzo Berardesca Received: 1 April 2022 Accepted: 23 May 2022 Published: 30 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 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 (https:// creativecommons.org/licenses/by/ 4.0/). cosmetics Review Clinical Translation of Microbiome Research in Alopecia Areata: A New Perspective? Fabio Rinaldi , Anna Trink, Angela Papale, Giammaria Giuliani and Daniela Pinto * Human Advanced MicrobiomeProject-HMAP, 20129 Milan, Italy; fabio.rinaldi@studiorinaldi.com (F.R.); anna.trink.1881@gmail.com (A.T.); apapale@giulianipharma.com (A.P.); ggiuliani@giulianipharma.com (G.G.) * Correspondence: dpinto@giulianipharma.com Abstract: The continuous research advances in the microbiome field is changing clinicians’ points of view about the involvement of the microbiome in human health and disease, including autoimmune diseases such as alopecia areata (AA). Both gut and cutaneous dysbiosis have been considered to play roles in alopecia areata. A new approach is currently possible owing also to the use of omic techniques for studying the role of the microbiome in the disease by the deep understanding of microorganisms involved in the dysbiosis as well as of the pathways involved. These findings suggest the possibility to adopt a topical approach using either cosmetics or medical devices, to modulate or control, for example, the growth of overexpressed species using specific bacteriocins or postbiotics or with pH control. This will favour at the same time the growth of beneficial bacteria which, in turn, can impact positively both the structure of the scalp ecosystem on the host’s response to internal and external offenders. This approach, together with a “systemic” one, via oral supplementation, diet, or faecal transplantation, makes a reliable translation of microbiome research in clinical practice and should be taken into consideration every time alopecia areata is considered by a clinician. Keywords: alopecia areata; microbiota; omics; postbiotics 1. Alopecia Areata and Microbiota—A Short History Alopecia areata (AA) is the second most common type of hair loss disorder in humans, with a reported lifetime incidence risk of higher than 2% [1,2]. It is classified as a non-scarring autoimmune hair disorder that manifests itself as a conse- quence of many etiological drivers mainly genetic, environmental, and immunological [3,4]. In particular, immunity is reported to play a pivotal role [5,6]. Immune privilege (IP) collapse of the hair follicle (HF) was first described by Billing- ham and Silvers in 1971 [7], by the suggestion that human HFs represent an IP site. Fol- lowing this, Kang et al. [8] demonstrated the downregulation of the expression of several genes important for the immunosuppressive environment in AA subjects. Currently, the central role of IP collapse in AA pathobiology has become widely accepted in the field, with current evidence suggesting that IP in the anagen HF can sequester antigens that are produced in hair bulbs from immune recognition [9,10]. The IP collapse is a recognised prerequisite for the development of AA [11], and the mechanisms behind have been highlighted [12]. One important key factor is the upregulation of MICA or ULBP3 which are NKG2D-activating ligands [13–16]. The continuous research advances in the microbiome field are changing clinicians’ points of view about the involvement of the microbiome in human health and disease, including autoimmune diseases such as AA. Recently, Scharschmidt et al. [17] suggested an involvement also of the HF’s micro- biome on IP given the modulatory activity of the microbiome itself on the balance between chemokine secreted by keratinocytes and IP guardian secretion. Cosmetics 2022, 9, 55. https://doi.org/10.3390/cosmetics9030055 https://www.mdpi.com/journal/cosmetics