# Dermatological Health in the Light of Skin Microbiome Evolution

Diala Haykal, Hugues Cartier, Brigitte Dréno

<figure><img src="image_1.png" /></figure>

## To cite this version:

Diala Haykal, Hugues Cartier, Brigitte Dréno. Dermatological Health in the Light of Skin Microbiome Evolution. Journal of Cosmetic Dermatology, 2024, 10.1111/jod.16557. hal-04753380

HAL Id: hal-04753380

https://nantes-universite.hal.science/hal-04753380v1

Submitted on 26 May 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_3.png" /></figure>

REVIEW ARTICLE

OPEN ACCESS

# Dermatological Health in the Light of Skin Microbiome Evolution

Diala Haykal¹ | Hugues Cartier² | Brigitte Dréno³

¹Centre Laser Palaiseau, Palaiseau, France | ²Centre Médical Saint Jean, Arras, France | ³Department of Dermato-Cancerology, CHU Nantes—Hôtel-Dieu CRCINA, Nantes, France

**Correspondence:** Diala Haykal (docteur.haykal@gmail.com)

**Received:** 10 June 2024 | **Revised:** 12 August 2024 | **Accepted:** 20 August 2024

**Funding:** The authors received no specific funding for this work.

**Keywords:** bacteriotherapy | dysbiosis | microorganisms | phages | probiotic | skin aging | skin conditions | skin microbiome | skin microbiota | skin transplantation

## ABSTRACT

**Background:** The complex ecosystem of the skin microbiome is essential for skin health by acting as a primary defense against infections, regulating immune responses, and maintaining barrier integrity. This literature review aims to consolidate existing information on the skin microbiome, focusing on its composition, functionality, importance, and its impact on skin aging.

**Methods:** An exhaustive exploration of scholarly literature was performed utilizing electronic databases including PubMed, Google Scholar, and ResearchGate, focusing on studies published between 2011 and 2024. Keywords included "skin microbiome," "skin microbiota," and "aging skin." Studies involving human subjects that focused on the skin microbiome's relationship with skin health were included. Out of 100 initially identified studies, 70 met the inclusion criteria and were reviewed.

**Results:** Studies showed that aging is associated with a reduction in the variety of microorganisms of the skin microbiome, leading to an increased susceptibility to skin conditions. Consequently, this underlines the interest in bacteriotherapy, mainly topical probiotics, to reinforce the skin microbiome in older adults, suggesting improvements in skin health and a reduction in age-related skin conditions. Further exploration is needed into the microbiome's role in skin health and the development of innovative, microbe-based skincare products. Biotherapeutic approaches, including the use of phages, endolysins, probiotics, prebiotics, postbiotics, and microbiome transplantation, can restore balance and enhance skin health. This article also addresses regulatory standards in the EU and the USA that ensure the safety and effectiveness of microbial skincare products.

**Conclusion:** This review underscores the need to advance research on the skin microbiome's role in cosmetic enhancements and tailored skincare solutions, highlighting a great interest in leveraging microbial communities for dermatological benefits.

## 1 | Introduction

Human skin, as big as 2m², is the largest organ. The skin microbiome, consisting of a wide range of microorganisms, has a crucial function in preserving skin health and balance. The skin microbiome has been significantly transformed by recent progress in sequencing technologies, leading to a profound enhancement in our comprehension of its composition, diversity, and function [1, 2]. The human skin microbiome is a diverse and ever-changing

ecosystem made up of a variety of microorganisms that live in different areas of the skin [2]. It is essential for skin health as it supports the skin's barrier function and immune system. The microbiome is formed in infancy and is shaped by genetics, environmental influences, and lifestyle decisions. Imbalance in the skin microbiota, known as dysbiosis, can result in a range of skin conditions such as infections, allergies, and autoimmune diseases [3]. Comprehending the structure and behavior of the skin microbiome is crucial for creating methods to enhance skin well-being

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.

© 2024 The Author(s). *Journal of Cosmetic Dermatology* published by Wiley Periodicals LLC.
and address aging skin [4, 5]. Current research seeks to clarify the
complex connection between the skin microbiome and host phys-
iology, leading to new approaches in skincare and dermatology.
The objective of this literature review is to consolidate existing
information on the skin microbiome, with a specific emphasis on
its composition, functionality, importance, and impact on skin
aging. This piece addresses the evolution of skin microbiome from
early life until old age, casting light on the most influential factors
in its changes. Aging skin microbiome undergoes several types of
changes depending on external and internal factors such as phys-
iological age, lifestyle, diseases, exposome, etc. These changes
verify the results of different therapeutic strategies. These ther-
apies often go through some regulatory principles which require
further improvement.

## 2 | Methods

An exhaustive exploration of scholarly literature was performed utilizing electronic databases including PubMed, Google Scholar, and ResearchGate. Relevant studies published between 2011 and 2024 were identified using keywords: “skin microbiome,” “skin microbiota,” and “aging skin.” Studies were included if they involved human subjects, focused on the skin microbiome and its relationship with skin health, and provided clear definitions and measurements of dermatological health. A total of 100 studies were initially identified through this search process. Out of the 100 identified studies, 12 duplicates were excluded, resulting in 88 studies that were screened based on their titles and abstracts. During this screening process, an additional six studies were excluded due to irrelevance with preliminary inclusion criteria. Subsequently, 82 studies were assessed for full-text eligibility. Upon further review, 12 studies were excluded owing to divergence of their content from the main topic of the present study. Finally, 70 studies met the criteria for relevance with skin microbiome and skin wellness and were thus considered eligible for inclusion in the review (Figure 1).

The included studies were categorized based on a holistic approach to the evolution of the skin microbiome. With this perspective in mind, the present review is composed of five sections,

<figure><img src="image_4.png" /><figcaption>**FIGURE 1** | Flowchart.</figcaption></figure>

covering various aspects of skin microbiome and its impact on
overall skin health, in addition to regulatory frameworks and
future perspectives (Table 1).

3 | Results

**3.1 | Skin Microbiome Composition**

The skin microbiome consists mainly of bacteria, fungi, and viruses making up a wide range of microbial species. A single square centimeter contains up to one million microorganisms. The skin microbiome, consisting of fungi, viruses, archaea, and mites, starts forming at birth and experiences substantial transformations over human lifetime [6]. During birth, the skin is first inhabited by germs from the mother's microbiota and the nearby surroundings. Early colonization is affected by factors such as delivery method (vaginal birth or cesarean section), infant food (breastfed or formula-fed), and antibiotic use. Infants delivered vaginally acquire their initial microbiota from their mothers' vaginal and fecal flora, fostering a microbial community that supports healthy immune and metabolic development. Conversely, cesarean-delivered infants often have a microbiome more reflective of skin and hospital environments, which may predispose them to allergies, asthma, and obesity. The nature of an infant's diet also shapes their gut microbiome; breastfed infants generally harbor a microbiome rich in beneficial bacteria like *Lactobacillus* and *Bifidobacterium*, supported by human milk oligosaccharides that promote a protective gut environment. Formula-fed infants, however, tend to develop a more varied microbiota from an earlier age, which can impact immune function differently by potentially reducing the abundance of beneficial bacteria such as *Bifidobacterium* and *Lactobacillus*, leading to an increased risk of allergies, asthma, and obesity due to less optimal development of the gut and skin immune systems [7, 8]. Additionally, antibiotic use during early life can disrupt these microbial communities, reducing diversity and depleting key bacterial populations which can have lasting effects on the child's health, increasing susceptibility to infections and possibly influencing lifelong health outcomes [9].

The skin microbiome changes as we get older due to genetic
factors, environmental exposures, lifestyle choices, and phys-
iological changes in the body as well. Genetic predispositions
influence skin reactions and microbial resilience, while envi-
ronmental factors like UV radiation and pollution can alter
microbial habitats and introduce harmful species. Lifestyle
choices, including diet and skincare routines, directly impact
microbial balance; for example, high-fat diets and harsh soaps
can disrupt this balance, whereas nutrient-rich foods and
gentle skincare products support it [10]. Additionally, physio-
logical changes such as decreased sebum production, thinner
skin, and altered pH levels provide a different environment
that affects microbial growth, potentially leading to skin con-
ditions linked to aging. Hormonal changes throughout pu-
erty can impact the skin's sebum production and microbial
composition, resulting in disorders such as acne. During ma-
turity, the microbiome reaches a stable state but remains sus-
ceptible to exposome and influences including food, hygiene
habits, skincare products, and exposure to contaminants [11].
Consequently, imbalances in the skin microbiome have been
<table><caption>TABLE 1 | Summary.</caption><thead><tr><td>References</td><td>Authors</td><td>Year</td><td>Findings</td><td>Type of research</td></tr></thead><tbody><tr><td>1</td><td>Eisenstein</td><td>2020</td><td>Describes the complex ecosystem of the skin microbiome and its importance for skin health</td><td>Review</td></tr><tr><td>2</td><td>Grice et al.</td><td>2011</td><td>Explores the skin microbiome and its interactions with the human host</td><td>Review</td></tr><tr><td>3</td><td>Skowron et al.</td><td>2021</td><td>Examines the impact of intrinsic and extrinsic factors on skin microbiota composition</td><td>Review</td></tr><tr><td>4</td><td>Smythe et al.</td><td>2023</td><td>Reviews research on skin microbiome and its effects on aging</td><td>Review</td></tr><tr><td>5</td><td>Harris-Tyon et al.</td><td>2022</td><td>Discusses the role of the microbiota in maintaining skin barrier function</td><td>Review</td></tr><tr><td>6</td><td>Habeebuddin et al.</td><td>2022</td><td>Investigates the potential benefits of topical probiotics for balanced skin microbiota</td><td>Review</td></tr><tr><td>7</td><td>Serghiou et al.</td><td>2023</td><td>Provides insights into recent research on early life skin microbiome</td><td>Review</td></tr><tr><td>8</td><td>Scharschmidt et al.</td><td>2013</td><td>Explores the ecology, genomics, and therapeutic potential of the skin microbiome</td><td>Review</td></tr><tr><td>9</td><td>Xu et al.</td><td>2019</td><td>Analyzes the relationship between acne, the skin microbiome, and antibiotic treatment</td><td>Review</td></tr><tr><td>10</td><td>Moitinho-Silva et al.</td><td>2022</td><td>Studies the association between host genetic factors and skin microbiota composition</td><td>Observational study</td></tr><tr><td>11</td><td>Boxberger et al.</td><td>2021</td><td>Highlights the role of intrinsic and extrinsic factors in shaping the bacterial communities of skin microbiome</td><td>Review</td></tr><tr><td>12</td><td>Yang et al.</td><td>2022</td><td>Summarizes recent advances in digital microfluidic-based platforms in evaluating skin microbiome</td><td>Review</td></tr><tr><td>13</td><td>Gallo et al.</td><td>2017</td><td>Discusses the role of the skin as an epithelial surface for microbial interaction</td><td>Commentary</td></tr><tr><td>14</td><td>Callewaert et al.</td><td>2020</td><td>Examines how changes in lifestyle and living environment can impact the skin microbiome and skin health and disease in humans</td><td>Review</td></tr><tr><td>15</td><td>Zhu et al.</td><td>2023</td><td>Analyzes the balance between health and disease in human skin bacterial microbiota</td><td>Review</td></tr><tr><td>16</td><td>McCarthy et al.</td><td>2022</td><td>Investigates the altered skin and gut microbiome in hidradenitis suppurativa</td><td>Observational study</td></tr><tr><td>17</td><td>Chambers et al.</td><td>2020</td><td>Reviews the impact of aging on skin barrier immunity</td><td>Review</td></tr><tr><td>18</td><td>Baldwin et al.</td><td>2017</td><td>Discusses the importance of maintaining cutaneous microbiota harmony for skin health</td><td>Review</td></tr><tr><td>19</td><td>Johnson et al.</td><td>2018</td><td>Explores new molecular targets to promote wound healing through the cutaneous microbiome</td><td>Review</td></tr><tr><td>20</td><td>Demessant-Flavigny et al.</td><td>2023</td><td>Reviews the role of Staphylococcus aureus in atopic dermatitis and skin microbiome dysbiosis</td><td>Review</td></tr><tr><td>21</td><td>Dessinioti et al.</td><td>2024</td><td>Analyzes perspectives for treating acne through the microbiome</td><td>Review</td></tr><tr><td>22</td><td>Myers et al.</td><td>2023</td><td>Identifies potential microbial features associated with skin aging</td><td>Multi-study analysis</td></tr></tbody></table>

(Continues)
<table><caption>TABLE 1 | (Continued)</caption><thead><tr><td>References</td><td>Authors</td><td>Year</td><td>Findings</td><td>Type of research</td></tr></thead><tbody><tr><td>23</td><td>Ratanapokasatit et al.</td><td>2022</td><td>Analyzes the skin interactome role in skin aging and skin health</td><td>Review</td></tr><tr><td>24</td><td>Nakatsuji et al.</td><td>2021</td><td>Explores mechanisms for controlling skin immune function through the microbiome</td><td>Review</td></tr><tr><td>25</td><td>Hurlow et al.</td><td>2011</td><td>Reviews the issue of dry skin in older adults</td><td>Review</td></tr><tr><td>26</td><td>Jugé et al.</td><td>2018</td><td>Examines shifts in skin microbiota composition across aging in Western European women</td><td>Research study</td></tr><tr><td>27</td><td>Dréno et al.</td><td>2016</td><td>Updates dermatologists on the healthy skin microbiome</td><td>Review</td></tr><tr><td>28</td><td>Byrd et al.</td><td>2018</td><td>Provides a comprehensive overview of the human skin microbiome</td><td>Review</td></tr><tr><td>29</td><td>Kano et al.</td><td>2013</td><td>Shows that fermented milk containing <i>Bifidobacterium breve</i> benefits skin condition in healthy adult women</td><td>Clinical trial</td></tr><tr><td>30</td><td>Woo et al.</td><td>2024</td><td>Reviews the interaction between the microbiota and the skin barrier in aging skin</td><td>Review</td></tr><tr><td>31</td><td>Sharma et al.</td><td>2016</td><td>Explores anti-aging effects of probiotics on the skin</td><td>Review</td></tr><tr><td>32</td><td>Dimarzio et al.</td><td>2008</td><td>Shows that topical application of bacterial sphingomyelinase increases skin-ceramide levels in aged subjects</td><td>Clinical trial</td></tr><tr><td>33</td><td>Notay et al.</td><td>2020</td><td>Analyzes the cosmetic improvement of facial wrinkles using topical <i>Nitrosomonas eutropha</i></td><td>Clinical trial</td></tr><tr><td>34</td><td>Weyrich et al.</td><td>2015</td><td>Examines associations between altered microbial communities and skin diseases</td><td>Review</td></tr><tr><td>35</td><td>Rocha et al.</td><td>2018</td><td>Explores the relationship between skin barrier function and the microbiome in acne</td><td>Review</td></tr><tr><td>36</td><td>Kang et al.</td><td>2009</td><td>Shows antimicrobial activity of enterocins against <i>Propionibacterium acnes</i></td><td>Experimental study</td></tr><tr><td>37</td><td>Lee et al.</td><td>2019</td><td>Provides a comprehensive review of the potential role of the microbiome in acne</td><td>Review</td></tr><tr><td>38</td><td>Thio et al.</td><td>2018</td><td>Discusses the microbiome perspective in psoriasis and psoriatic arthritis</td><td>Review</td></tr><tr><td>39</td><td>França et al.</td><td>2021</td><td>Reviews the use of topical probiotics in dermatological therapy and skincare</td><td>Review</td></tr><tr><td>40</td><td>Guéniche et al.</td><td>2006</td><td>Shows improvement in atopic dermatitis symptoms by <i>Vitreoscilla filiformis</i> bacterial extract</td><td>Clinical trial</td></tr><tr><td>41</td><td>Guéniche et al.</td><td>2008</td><td>Demonstrates improvement in seborrheic dermatitis with <i>Vitreoscilla filiformis</i> biomass</td><td>Clinical trial</td></tr><tr><td>42</td><td>Chen et al.</td><td>2013</td><td>Discusses current perspectives and future challenges in skin microbiome research</td><td>Review</td></tr><tr><td>43</td><td>Carvalho et al.</td><td>2023</td><td>Reviews the impact of cosmetic products on the skin microbiota</td><td>Review</td></tr><tr><td>44</td><td>Bouslimani et al.</td><td>2019</td><td>Analyzes the dynamics of skin chemistry and microbiome with the use of skincare products</td><td>Observational Study</td></tr></tbody></table>

(Continues)
<table><caption>TABLE 1 | (Continued)</caption><thead><tr><td>References</td><td>Authors</td><td>Year</td><td>Findings</td><td>Type of research</td></tr></thead><tbody><tr><td>45</td><td>Wallen-Russell et al.</td><td>2019</td><td>Explores the effects of everyday cosmetics on the skin microbiome using biodiversity as a measure</td><td>Observational study</td></tr><tr><td>46</td><td>Ch'ng</td><td>2024</td><td>Shows the effectiveness of an emollient "plus" in rebalancing the skin microbiome for managing atopic dermatitis.</td><td>Clinical trial</td></tr><tr><td>47</td><td>Sarasati et al.</td><td>2023</td><td>Investigates the potential of plant-derived exosome-like nanoparticles for biomedical and regenerative applications</td><td>Experimental study</td></tr><tr><td>48</td><td>Bai et al.</td><td>2024</td><td>Examines clinical applications of exosomes in cosmetic dermatology</td><td>Review</td></tr><tr><td>49</td><td>Ghasemian</td><td>2021</td><td>Explores the application of exosome-derived mesenchymal stem cells in treating fungal diseases</td><td>Experimental study</td></tr><tr><td>50</td><td>Dagnelie et al.</td><td>2020</td><td>Highlights the role of bacterial extracellular vesicles in inflammatory dermatoses</td><td>Review</td></tr><tr><td>51</td><td>Hendricks et al.</td><td>2019</td><td>Discusses the knowns, unknowns, and emerging trends of skin bacterial transplants in atopic dermatitis</td><td>Review</td></tr><tr><td>52</td><td>Natarelli et al.</td><td>2023</td><td>Explores the role of bacteriophages and the phageome in dermatology</td><td>Review</td></tr><tr><td>53</td><td>Özal et al.</td><td>2022</td><td>Provides a systematic review of bacteriophages and endolysins for reducing microorganisms</td><td>Systematic review</td></tr><tr><td>54</td><td>Castillo-González et al.</td><td>2022</td><td>Discusses the therapeutic potential of bacteriotherapy with human skin commensals in atopic dermatitis</td><td>Review</td></tr><tr><td>55</td><td>Dewi et al.</td><td>2023</td><td>Examines the possibilities of bacteriotherapy for skin aging and atopic dermatitis</td><td>Review</td></tr><tr><td>56</td><td>Smirnova et al.</td><td>2023</td><td>Reviews new bacteriotherapy approaches for inflammatory skin diseases</td><td>Review</td></tr><tr><td>57</td><td>Ito et al.</td><td>2022</td><td>Shows the effect of emollients containing vegetable-derived lactobacillus in treating atopic dermatitis symptoms</td><td>Review</td></tr><tr><td>58</td><td>Park et al.</td><td>2014</td><td>Studies the transfer of skin microbiota between dissimilar autologous microenvironments</td><td>Clinical trial</td></tr><tr><td>59</td><td>Perin et al.</td><td>2019</td><td>Investigates the effects of human skin microbiota transplantation in models of atopic dermatitis</td><td>Pilot study</td></tr><tr><td>60</td><td>Myles et al.</td><td>2016</td><td>Discusses regulatory aspects of probiotics and microbial products in skincare</td><td>Experimental study</td></tr><tr><td>61</td><td>Wright et al.</td><td>2020</td><td>Reviews the role of regulatory agencies in pharmaceuticals and cosmetics</td><td>Review</td></tr><tr><td>62</td><td>Yingling et al.</td><td>2000</td><td>Explores the evolving use of probiotics and postbiotics in cosmetics and their regulatory aspects</td><td>Review</td></tr><tr><td>63</td><td>Arora et al.</td><td>2023</td><td>Analyzes the applications of machine learning and deep learning in microbiome research</td><td>Review</td></tr><tr><td>64</td><td>Hernández et al.</td><td>2022</td><td>Reviews challenges and best practices in applying machine learning to microbiome research</td><td>Review</td></tr><tr><td>65</td><td>Papoutsoglou et al.</td><td>2023</td><td>Highlights the potential of biosensors and AI in dermatology</td><td>Review</td></tr></tbody></table>

(Continues)
<table><caption>TABLE 1 | (Continued)</caption><thead><tr><td>References</td><td>Authors</td><td>Year</td><td>Findings</td><td>Type of research</td></tr></thead><tbody><tr><td>66</td><td>Haykal</td><td>2024</td><td>Introduces biosensors and their applications</td><td>Review</td></tr><tr><td>67</td><td>Bhalla et al.</td><td>2016</td><td>Explores the use of flexible and printable integrated biosensors for monitoring skin conditions</td><td>Review</td></tr><tr><td>68</td><td>Wang et al.</td><td>2023</td><td>Discusses dermal tattoo biosensors and their potential applications</td><td>Experimental study</td></tr><tr><td>69</td><td>Dhond et al.</td><td>2023</td><td>Reviews the impact of modern environments on skin microbiome, barrier integrity, and immune programming</td><td>Review</td></tr><tr><td>70</td><td>Prescott et al.</td><td>2017</td><td>Highlights the role of modern environments on skin microbiome and health</td><td>Review</td></tr></tbody></table>

associated with a range of skin disorders such as eczema, psoriasis, acne, and rosacea. It is essential to comprehend the evolution and alterations in the skin microbiome from infancy to old age to enhance skin health and address dermatological issues effectively [12].

## 3.2 | Role of the Skin Microbiome in Dermatological Health

The common notion that human skin has an average surface area of 2 m² fails to acknowledge the complexity of the skin, which includes approximately 5 million appendages, potentially elevating the total surface area to approximately 25 m², making it the largest organ [13]. The 2–3 mm deep outer layer of the skin not only serves as an immunological barrier that protects the body from environmental factors, injuries, and infections, but also regulates temperature, prevents water loss, and facilitates vitamin D synthesis, highlighting the crucial role of the skin microbiome in maintaining overall skin health [2]. Skin health, in the field of dermatology within broad terms, refers to the optimal functioning and appearance of the skin, encompassing its protective barrier functions, temperature regulation, and support for overall bodily health. From a holistic approach, skin health is seen as the harmonious balance of all skin components, including the skin microbiome, immune system, and structural integrity, which work together to maintain the skin's resilience and its ability to protect against environmental stressors and infections. Accumulating evidence indicates that the skin microbiome has a vital function in preserving the balance of the skin and defending against harmful microorganisms. Commensal microorganisms engage in competition with potential pathogens for colonization sites and nutrients, thereby inhibiting the excessive growth of pathogenic species [14, 15]. Furthermore, the skin microbiome plays a role in controlling nearby immune reactions (innate immunity), impacting pathways related to inflammation and defense against microorganisms [3, 16]. The skin microbiome itself is integral to the modulation of these immune activities [17]. Commensal bacteria on the skin contribute to the education and regulation of the immune system including both innate and adaptive immunity, teaching immune cells to tolerate beneficial microbes while remaining vigilant against

pathogens [18]. The imbalance of the skin microbiome has been linked to several dermatological conditions, such as acne vulgaris, atopic dermatitis (AD), psoriasis, wound infections, and skin aging [19–23].

## 3.3 | Microbiome Diversity in Aging Skin: Impact on Aging Process and Dermatological Diseases Development

Research examining the relationship between aging skin and the skin microbiome has yielded insightful findings. This includes studying the impact of microbial metabolites, immune modulation, and tissue remodeling on age-related changes in the skin [24]. To be specific, as the skin microenvironment changes by age, so does the skin microbial composition. To name a few of these changes, small blood vessels, sebaceous glands, and sweat glands shrink over time along with a decrease in nutrient supply [25]. In this regard, Jugé et al. [26] conducted a study revealing age-related changes in microbial diversity, noting a decline with age and an increase in certain pathogenic species such as Proteobacteria and *Corynebacterium* spp. To investigate the impact of skin microbiome on different aging processes, Dréno et al. conducted a longitudinal investigation that explored the impact of chronological aging and photoaging on the skin microbiome, revealing distinct microbial signatures associated with different aging processes. They found that the skin microbiome changes significantly with age. This shift in microbiome composition is linked to decreased sebum production, thinner skin, and altered pH levels, creating a more favorable environment for pathogenic species and contributing to age-related skin conditions. In younger individuals, there's a higher diversity of bacteria, including more *Cutibacterium* species, which thrive in oily skin. As skin ages, microbial diversity decreases, with an increase in species like *Staphylococcus* and *Corynebacterium*, linked to reduced sebaceous activity and immune changes. Photoaging further alters the microbiome, increasing species associated with dry, less resilient skin. These microbial shifts may contribute to the clinical signs of aging skin, such as dryness and reduced elasticity [27]. Furthermore, review articles by Byrd et al., Kano et al., and Woo et al. provided comprehensive overviews of the impact of the skin microbiome on age-associated skin conditions and explored the effects of probiotic supplementation on the skin
microbiome of elderly individuals, respectively [28–30]. Byrd, Belkaid, and Segre [28] refer to the diversity of microbial derma-tological disease drivers in diabetic and obese elderly. Kano et al. [29] have referred to certain diets such as yogurt intake to have direct positive effect on adult females with chronic constipation and dry skin. Woo and Kim [30] point out that gut dysbiosis is directly involved in the skin microbiome and various dermato-logical conditions such as acne, eczema, rosacea, prurigo nodu-laris, and skin cancer. Collectively, these studies highlight the intricate interplay between aging skin and the skin microbiome, suggesting potential avenues for interventions to maintain skin health and mitigate age-related skin changes. Other investiga-tions conducted by Habeebuddin et al., Chambers et al., Sharma et al., Dimarzio et al., and Notay et al. shed light on the potential of topical probiotics to improve skin health and modify the skin microbiome among the elderly, thereby indicating the efficacy of therapeutic cosmetic treatments [6, 17, 31–33]. Their results suggest that a topical probiotic at a high concentration effec-tively reduces the severity of facial wrinkles in contrast to lower concentrations. Overall, these studies emphasize the dynamic relationship between aging skin and the skin microbiome, un-derscoring the importance of microbial dysbiosis in age-related skin changes and highlighting avenues for further research and intervention development. Additionally, research by Weyrich et al. [34] focused on the role of the skin microbiome in age-related inflammatory skin conditions, demonstrating dysbiosis and alterations in microbial metabolites in elderly individuals with dermatitis. Furthermore, several research investigated the direct relationship between skin microbiome dysbiosis and der-matological conditions such as rosacea, acne vulgaris, psoriasis, and AD [12, 35–42]. Moreover, changes in the microbiome com-position can influence systemic immune responses, potentially affecting overall health and susceptibility to other diseases. This compromised barrier function can lead to an increased suscep-tibility to skin infections and colonization by potentially patho-genic microorganisms. For instance, older adults are more prone to infections like cellulitis, fungal foot infections, and shingles, which are caused by the reactivation of the varicella-zoster virus.

Overall, the skin interactome combines the genome, microbiome, and exposome, impacting skin aging and health [14]. We must now focus on the maintenance of ideal skin conditions through reducing the negative impacts of factors affecting the skin interactome to prevent premature aging. Although there is a lack of sufficient clinical research on skin anti-aging treatments, the increasing interest in this developing field highlights the need for more investigation, which could lead to future therapeutic breakthroughs.

**3.4 | Microbiome-Mediated Responses to Cosmetic Procedures**

There is a critical need for more comprehensive, long-term studies to investigate the impact of cosmetic skincare products and procedures, including laser therapy, chemical peels, and injectables, on the skin microbiome. However, emollients containing prebiotics have been shown to support the growth of beneficial skin bacteria, maintaining the skin barrier and microbial balance. Furthermore, understanding how changes in the microbiome affect treatment outcomes and post-procedure complications is

essential for grasping the intricate dynamics of microbiome alterations, highlighting a crucial area of focus in healthcare [43]. In addition, there is a need to create prediction algorithms that may customize therapies according to individual microbiome profiles to improve safety and effectiveness. There are several studies highlighting the effects of cosmetic procedures and products on the skin microbiome, revealing various outcomes based on the nature of the products used and the specifics of the procedures involved. One study explored the dynamics of the skin microbiome over a 9-week period involving regular use of different personal care products like deodorants and moisturizers. This research demonstrated that these products alter the microbial diversity of the skin through the persistence of product ingredients like polyethylene glycol in the skin's microbiome [44]. Another research focused on the impact of everyday cosmetics on skin health, particularly how synthetic ingredients might damage the skin microbiome. This study used different types of face washes, including those with synthetic ingredients versus completely natural ones, to evaluate their effects on skin's microbial diversity, pH, moisture, and trans-epidermal water loss. The findings suggested a potential link between synthetic cosmetics and reduced microbiome biodiversity, which might impair skin health and thereby accelerate aging [45]. Another study explores the critical role of the skin microbiome in managing AD, emphasizing that dysbiosis can exacerbate the condition by disrupting the skin barrier and immunity. It highlights the effectiveness of an emollient “plus,” which includes active ingredients such as *Vitreoscilla filiformis* and microresyl, designed to rebalance the skin microbiome and reduce inflammation. This type of emollient has been shown to modulate the skin microbiome more effectively than standard emollients, thereby improving AD symptoms and reducing disease severity [46]. Additionally, exosomes, small extracellular vesicles crucial for cell communication, have been researched for their potential impact on the skin microbiome, with studies suggesting that they significantly contribute to skin health. By facilitating communication between cells by transferring proteins, lipids, and genetic materials, exosomes can affect the behavior and composition of the skin microbiota. This interaction could help enhance skin barrier functions, modulate immune responses, and directly affect microbial composition, promoting a healthier skin environment. Both plant and human-derived exosomes contribute uniquely to skin health through their interactions with the skin microbiome, each leveraging their molecular properties to support skin integrity and function. Specifically, plant-derived exosomes provide immediate, surface-level benefits such as enhanced protection and hydration, while human-derived exosomes contribute to deeper, more systemic improvements in skin health and cellular communication [47, 48]. Although the precise mechanisms and outcomes of these interactions remain under active investigation, preliminary findings suggest that dermatological treatments utilizing exosomes hold promise for maintaining or restoring a balanced skin microbiome, thus opening new pathways for innovative therapeutic strategies [49, 50].

**3.5 | The Impact of Bacteriophages, Endolysins, Probiotics, and Skin Transplantation on the Microbiome**

The current section will review the transformative potential of bacteriotherapy in dermatology, focusing on its efficacy in
managing the skin microbiome and enhancing skin health amidst aging. Biotherapeutic approaches include using phages, endolysins, probiotics, prebiotics, postbiotics, and microbiome transplantation to restore balance and enhance skin health. Research has shown reassuring results in using targeted bacterial therapies to combat pathogenic bacteria and reinforce the skin's natural defenses [51–53].

Bacteriophages and endolysins are assessed for their targeted antimicrobial actions which could selectively eliminate pathogenic bacteria, thereby restoring a balanced skin microbial environment. The review by Ito and Amagai dives into the implications of skin microbiota for health and therapeutic strategies, emphasizing the reliability of bacteriotherapy to treat skin conditions. Bacteriotherapy involves using live bacteria or their products to modify the skin microbiome, aiming to restore balance and enhance skin health. This approach is particularly highlighted in the context of treating skin diseases such as AD, where specific beneficial bacteria or their enzymes are applied to the skin to improve barrier function and reduce pathogenic bacteria [54–56]. The therapeutic potential of these strategies is substantial, given their ability to harness the natural properties of the skin's microbiota. However, the review does not specifically focus on aging but rather on broader applications, suggesting that further research is needed to explore and optimize these bacterial therapies for various skin health aspects, potentially including aging in future studies [57].

The roles of pro-, pre-, and postbiotics are explored in terms of their ability to foster a beneficial microbial flora, enhance skin barrier functions, and potentially reverse the effects of aging. Probiotics introduce beneficial bacteria to the skin, improving its natural defenses and barrier integrity, while prebiotics nourish these beneficial bacteria, promoting a balanced microbiome that supports overall skin health [58]. Postbiotics offer additional benefits such as anti-inflammatory and antioxidant properties, which are essential for repairing skin damage and reducing signs of aging. Together, these biotic elements create a synergistic approach to skincare, aiming to maintain skin resilience, hydration, and youthful appearance through advanced bioactive ingredients [33].

Another emerging scientific consensus points out that the skin microbiome plays a fundamental role in both the success of skin transplants and the management of skin diseases. Skin transplantation, especially in the context of burn injuries or chronic wounds, can significantly interact with and alter the skin microbiome. The transplanted skin not only brings its own microbiome but also needs to integrate with the recipient's existing microbial communities [59]. This integration is crucial for the success of the transplant, as a balanced microbiome can promote better wound healing and reduce infection risks. Furthermore, research suggests that understanding and potentially modifying the microbiome at the site of transplantation may enhance graft survival and overall skin health. The study of the skin microbiome's role in transplantation is still evolving; at the same time, it puts new horizons at sight in the field of microbiome-focused therapies in transplantations. Building on this concept, a study conducted by Myles et al. focuses on the role of skin transplantation in AD. In this experimental research, the team transplanted human skin microbiota into murine models to study its

influence on disease development. The findings suggest that altering the skin's microbial community can affect inflammation and disease outcome, indicating a potential therapeutic avenue for treating AD through microbiota manipulation. This study contributes to the growing understanding of skin transplantation and microbiome's role in immune responses and inflammatory diseases [60]. It suggests an approach that could lead to the development of microbiota-based therapies targeted at the underlying microbial imbalances, offering a personalized treatment option for patients suffering from various skin conditions.

## 3.6 | Regulatory Aspects

Probiotics and microbial products used in skin care and health applications are regulated by a comprehensive framework developed majorly within the European Union (EU) and the USA, ensuring consumer safety, efficacy, and truthful marketing on a global scale. Products are classified into distinct regulatory pathways determined by their intended use and associated health claims. These pathways may involve authorization at the EU level or notification by the US member states. The classification process is carried out under the supervision of the European Food Safety Authority and the European Medicines Agency. The jurisdiction in the USA where product classification and pre-market approval are regulated is the Food and Drug Administration. These frameworks exemplify cohesive and rigorous strategies for regulating microbial products and probiotics, with a focus on ensuring consumer safety, utilizing scientific evidence to support health claims, and adhering to ethical marketing standards [61, 62]. Within these frameworks, skincare products fall into various regulatory categories based on the type of the claim that are associated with them and whether they are administrated systemically or topically [63].

## 3.7 | Future Directions

The integration of predictive models and machine learning techniques significantly enhances our understanding of the complex relationships within the skin microbiome. These tools can meticulously analyze extensive data from longitudinal studies, pinpointing how variables like diet, lifestyle, and cosmetic consumption interact with the microbiome to influence skin aging [64, 65].

Future research on microbiome-mediated cosmetic responses covers several key areas. First, longitudinal studies are needed to understand the temporal dynamics of microbiome changes after different cosmetic interventions to better understand microbial resilience and recovery. In the future, integrating biosensors with the skin microbiota will transform healthcare. The advanced sensors will monitor biomarkers for disease detection and analyze interactions within the skin microbiome, offering personalized insights into skin health and wellness [66]. They can also reveal the microbial community's structure, function, and metabolic activity before and after procedures. Studying microbial biomarkers predictive of treatment outcomes and complications will enable personalized treatment strategies and risk assessment for cosmetic surgery patients. Utilizing this technology will enable individuals to actively oversee their well-being
with unprecedented precision and understanding [67-69]. Additionally, the development and use of 3D skin models can offer invaluable insights into how cosmetic treatments affect the skin microbiome in a controlled, replicable environment, enhancing our understanding of microbial interactions with skin tissues [11, 70]. Moreover, studying the skin microbiome and host immune responses post-treatment can reveal microbiome-mediated effects on treatment efficacy and adverse events [4, 23]. Finally, studies on microbiome-targeted interventions like probiotics or microbiome-modulating skincare products may improve cosmetic dermatology treatment outcomes and reduce post-procedural complications. In the light of the infinite potentials that the field of dermatology holds with regard to skin microbiota, future research should focus on the complex relationship between the skin microbiome and cosmetic procedures to develop personalized skin health and aesthetics treatments.

## 4 | Conclusion

The correlation between changes in the skin microbiota and the aging process is a significant area of focus in dermatological research, reflecting the complex interplay between microbial shifts and skin health over time. Evidence suggests that aging can lead to alterations in the skin environment, such as reduced lipid production and compromised barrier function, which in turn may favor the growth of certain microbial species while inhibiting others. These changes in the microbial landscape can influence the overall health and appearance of the skin, potentially exacerbating signs of aging. Conversely, emerging research also supports the idea that modifications in the skin microbiota itself might contribute directly to the aging process. For instance, an imbalance in microbial diversity or the overgrowth of pathogenic bacteria can provoke inflammatory responses, lead to oxidative stress, and cause tissue damage, all of which are key factors in the aging of skin. This suggests a potentially cyclical relationship where not only does aging affect microbial composition, but also changes in the microbiota may accelerate aging-related skin deterioration. However, several limitations in our review must be acknowledged. The observational nature of the reviewed studies prevents a definitive establishment of causality between the skin microbiota and aging. Additionally, the variability in study designs, populations, and methodologies introduces a degree of uncertainty regarding the generalizability of the findings. Finally, the dynamic nature of the skin microbiota, influenced by a wide range of external and internal factors such as diet, lifestyle, and cosmetic use, adds further complexity to isolating the specific effects of microbiota changes on skin aging. These factors must be meticulously addressed in future studies to provide more holistic insights on developing aging skin treatment strategies. However, the current study builds a bulk of literature review that can contribute to future perspectives in this field.

### Author Contributions

Diala Haykal wrote the manuscript, and Hugues Cartier and Brigitte Dréno reviewed it.

### Ethics Statement

The authors have nothing to report.

### Conflicts of Interest

The authors declare no conflicts of interest.

### Data Availability Statement

All information is included in the manuscript.

### References

1. M. Eisenstein, "The Skin Microbiome," *Nature* 588, no. 7838 (2020): S209, https://doi.org/10.1038/d41586-020-03523-7.

2. E. A. Grice and J. A. Segre, "The Skin Microbiome," *Nature Reviews. Microbiology* 9, no. 4 (2011): 244-253, https://doi.org/10.1038/nrmicro2537.

3. K. Skowron, J. Bauza-Kaszewska, Z. Kraszewska, et al., "Human Skin Microbiome: Impact of Intrinsic and Extrinsic Factors on Skin Microbiota," *Microorganisms* 9, no. 3 (2021): 543, https://doi.org/10.3390/microorganisms9030543.

4. P. Smythe and H. N. Wilkinson, "The Skin Microbiome: Current Landscape and Future Opportunities," *International Journal of Molecular Sciences* 24, no. 4 (2023): 3950, https://doi.org/10.3390/ijms24043950.

5. T. A. Harris-Tryon and E. A. Grice, "Microbiota and Maintenance of Skin Barrier Function," *Science* 376, no. 6596 (2022): 940-945, https://doi.org/10.1126/science.abo0693.

6. M. Habeebuddin, R. K. Karnati, P. N. Shiroorkar, et al., "Topical Probiotics: More Than a Skin Deep," *Pharmaceutics* 14, no. 3 (2022): 557, https://doi.org/10.3390/pharmaceutics14030557.

7. I. R. Serghiou, M. A. Webber, and L. J. Hall, "An Update on the Current Understanding of the Infant Skin Microbiome and Research Challenges," *Current Opinion in Microbiology* 75 (2023): 102364, https://doi.org/10.1016/j.mib.2023.102364.

8. T. C. Scharschmidt and M. A. Fischbach, "What Lives On Our Skin: Ecology, Genomics and Therapeutic Opportunities of the Skin Microbiome," *Drug Discovery Today: Disease Mechanisms* 10, no. 3 (2013): e83-e89, https://doi.org/10.1016/j.ddmec.2012.12.003.

9. H. Xu and H. Li, "Acne, the Skin Microbiome, and Antibiotic Treatment," *American Journal of Clinical Dermatology* 20, no. 3 (2019): 335-344, https://doi.org/10.1007/s40257-018-00417-3.

10. L. Moitinho-Silva, F. Degenhardt, E. Rodriguez, et al., "Host Genetic Factors Related to Innate Immunity, Environmental Sensing and Cellular Functions Are Associated With Human Skin Microbiota," *Nature Communications* 13, no. 1 (2022): 6204, https://doi.org/10.1038/s41467-022-33906-5.

11. M. Boxberger, V. Cenizo, N. Cassir, and B. La Scola, "Challenges in Exploring and Manipulating the Human Skin Microbiome," *Microbiome* 9, no. 1 (2021): 125, https://doi.org/10.1186/s40168-021-01062-5.

12. Y. Yang, L. Qu, I. Mijakovic, and Y. Wei, "Advances in the Human Skin Microbiota and Its Roles in Cutaneous Diseases," *Microbial Cell Factories* 21, no. 1 (2022): 176, https://doi.org/10.1186/s12934-022-01901-6.

13. R. L. Gallo, "Human Skin Is the Largest Epithelial Surface for Interaction With Microbes," *Journal of Investigative Dermatology* 137, no. 6 (2017): 1213-1214, https://doi.org/10.1016/j.jid.2016.11.045.

14. C. Callewaert, K. Ravard Helffer, and P. Lebaron, "Skin Microbiome and Its Interplay With the Environment," *American Journal of Clinical Dermatology* 21, no. 1 (2020): 4-11, https://doi.org/10.1007/s40257-020-00551-x.

15. Y. Zhu, X. Yu, and G. Cheng, "Human Skin Bacterial Microbiota Homeostasis: A Delicate Balance Between Health and Disease," *mLife* 2, no. 2 (2023): 107-120, https://doi.org/10.1002/mlf2.12064.

16. S. McCarthy, M. Barrett, S. Kirthi, et al., "Altered Skin and Gut Microbiome in Hidradenitis Suppurativa," *Journal of Investigative Dermatology* 137, no. 6 (2023): 107-120, https://doi.org/10.1002/jid.202300006.
Dermatology 142, no. 2 (2022): 459–468.e15, https://doi.org/10.1016/j.jid.2021.05.036.

17. E. S. Chambers and M. Vukmanovic-Stejic, "Skin Barrier Immunity and Ageing," *Immunology* 160, no. 2 (2020): 116–125, https://doi.org/10.1111/imm.13152.

18. H. E. Baldwin, N. D. Bhatia, A. Friedman, R. M. Eng, and S. Seite, "The Role of Cutaneous Microbiota Harmony in Maintaining a Functional Skin Barrier," *Journal of Drugs in Dermatology* 16, no. 1 (2017): 12–18.

19. T. R. Johnson, B. I. Gómez, M. K. McIntyre, et al., "The Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing," *International Journal of Molecular Sciences* 19, no. 9 (2018): 2699, https://doi.org/10.3390/ijms19092699.

20. A. L. Demessant-Flavigny, S. Connétable, D. Kerob, M. Moreau, L. Aguilar, and A. Wollenberg, "Skin Microbiome Dysbiosis and the Role of Staphylococcus Aureus in Atopic Dermatitis in Adults and Children: A Narrative Review," *Journal of the European Academy of Dermatology and Venereology* 37, no. Suppl 5 (2023): 3–17, https://doi.org/10.1111/jdv.19125.

21. C. Dessinioti and A. Katsambas, "The Microbiome and Acne: Perspectives for Treatment," *Dermatologic Therapy* 14, no. 1 (2024): 31–44, https://doi.org/10.1007/s13555-023-01079-8.

22. T. Myers, A. Bouslimani, S. Huang, et al., "A Multi-Study Analysis Enables Identification of Potential Microbial Features Associated With Skin Aging Signs," *Frontiers in Aging* 4 (2023): 1304705, https://doi.org/10.3389/fragi.2023.1304705.

23. Y. Ratanapokasatit, W. Laisuan, T. Rattananukrom, A. Petchlorian, I. Thaipisuttikul, and M. Sompornrattanaphan, "How Microbiomes Affect Skin Aging: The Updated Evidence and Current Perspectives," *Life* 12, no. 7 (2022): 936, https://doi.org/10.3390/life12070936.

24. T. Nakatsuji, J. Y. Cheng, and R. L. Gallo, "Mechanisms for Control of Skin Immune Function by the Microbiome," *Current Opinion in Immunology* 72 (2021): 324–330, https://doi.org/10.1016/j.coi.2021.09.001.

25. J. Hurlow and D. Z. Bliss, "Dry Skin in Older Adults," *Geriatric Nursing (New York, N.Y.)* 32, no. 4 (2011): 257–262, https://doi.org/10.1016/j.gerinurse.2011.03.003.

26. R. Jugé, P. Rouaud-Tinguely, J. Breugnot, et al., "Shift in Skin Microbiota of Western European Women Across Aging," *Journal of Applied Microbiology* 125, no. 3 (2018): 907–916, https://doi.org/10.1111/jam.13929.

27. B. Dréno, E. Araviiskaia, E. Berardesca, et al., "Microbiome in Healthy Skin, Update for Dermatologists," *Journal of the European Academy of Dermatology and Venereology* 30, no. 12 (2016): 2038–2047, https://doi.org/10.1111/jdv.13965.

28. A. L. Byrd, Y. Belkaid, and J. A. Segre, "The Human Skin Microbiome," *Nature Reviews. Microbiology* 16, no. 3 (2018): 143–155, https://doi.org/10.1038/nrmicro.2017.157.

29. M. Kano, N. Masuoka, C. Kaga, et al., "Consecutive Intake of Fermented Milk Containing Bifidobacterium Breve Strain Yakult and Galacto-Oligosaccharides Benefits Skin Condition in Healthy Adult Women," *Bioscience of Microbiota, Food and Health* 32, no. 1 (2013): 33–39, https://doi.org/10.12938/bmfh.32.33.

30. Y. R. Woo and H. S. Kim, "Interaction Between the Microbiota and the Skin Barrier in Aging Skin: A Comprehensive Review," *Frontiers in Physiology* 15 (2024): 1322205, https://doi.org/10.3389/fphys.2024.1322205.

31. D. Sharma, M. M. Kober, and W. P. Bowe, "Anti-Aging Effects of Probiotics," *Journal of Drugs in Dermatology* 15, no. 1 (2016): 9–12.

32. L. Dimarzio, B. Cinque, F. Cupelli, C. De Simone, M. G. Cifone, and M. Giuliani, "Increase of Skin-Ceramide Levels in Aged Subjects Following a Short-Term Topical Application of Bacterial Sphingomyelinase From *Streptococcus thermophilus*," *International Journal of Immunopathology and Pharmacology* 21, no. 1 (2008): 137–143, https://doi.org/10.1177/039463200802100115.

33. M. Notay, S. Saric-Bosanac, A. R. Vaughn, et al., "The Use of Topical Nitrosomonas eutropha for Cosmetic Improvement of Facial Wrinkles," *Journal of Cosmetic Dermatology* 19, no. 3 (2020): 689–693, https://doi.org/10.1111/jocd.13060.

34. L. S. Weyrich, S. Dixit, A. G. Farrer, A. J. Cooper, and A. J. Cooper, "The Skin Microbiome: Associations Between Altered Microbial Communities and Disease," *Australasian Journal of Dermatology* 56, no. 4 (2015): 268–274, https://doi.org/10.1111/ajd.12253.

35. M. A. Rocha and E. Bagatin, "Skin Barrier and Microbiome in Acne," *Archives of Dermatological Research* 310, no. 3 (2018): 181–185, https://doi.org/10.1007/s00403-017-1795-3.

36. B. S. Kang, J. G. Seo, G. S. Lee, et al., "Antimicrobial Activity of Enterocins From *Enterococcus faecalis* SL-5 Against *Propionibacterium acnes*, the Causative Agent in Acne Vulgaris, and Its Therapeutic Effect," *Journal of Microbiology* (Seoul, Korea) 47, no. 1 (2009): 101–109, https://doi.org/10.1007/s12275-008-0179-y.

37. Y. B. Lee, E. J. Byun, and H. S. Kim, "Potential Role of the Microbiome in Acne: A Comprehensive Review," *Journal of Clinical Medicine* 8, no. 7 (2019): 987, https://doi.org/10.3390/jcm8070987.

38. H. B. Thio, "The Microbiome in Psoriasis and Psoriatic Arthritis: The Skin Perspective," *Journal of Rheumatology. Supplement* 94 (2018): 30–31, https://doi.org/10.3899/jrheum.180133.

39. K. França, "Topical Probiotics in Dermatological Therapy and Skin-care: A Concise Review," *Dermatologic Therapy* 11, no. 1 (2021): 71–77, https://doi.org/10.1007/s13555-020-00476-7.

40. A. Guéniche, A. Hennino, C. Goujon, et al., "Improvement of Atopic Dermatitis Skin Symptoms by *Vitreoscilla filiformis* Bacterial Extract," *European Journal of Dermatology* 16, no. 4 (2006): 380–384.

41. A. Guéniche, A. C. Cathelineau, P. Bastien, et al., "*Vitreoscilla filiformis* Biomass Improves Seborrheic Dermatitis," *Journal of the European Academy of Dermatology and Venereology* 22, no. 8 (2008): 1014–1015, https://doi.org/10.1111/j.1468-3083.2007.02508.x.

42. Y. E. Chen and H. Tsao, "The Skin Microbiome: Current Perspectives and Future Challenges," *Journal of the American Academy of Dermatology* 69, no. 1 (2013): 143–155.e3, https://doi.org/10.1016/j.jaad.2013.01.016.

43. M. J. Carvalho, A. L. S Oliveira, S. Santos Pedrosa, M. Pintado, I. Pinto-Ribeiro, and A. R. Madureira, "Skin Microbiota and the Cosmetic Industry," *Microbial Ecology* 86, no. 1 (2023): 86–96, https://doi.org/10.1007/s00248-022-02070-0.

44. A. Bouslimani, R. da Silva, T. Kosciolek, et al., "The Impact of Skin Care Products on Skin Chemistry and Microbiome Dynamics," *BMC Biology* 17, no. 1 (2019): 47, https://doi.org/10.1186/s12915-019-0660-6.

45. C. Wallen-Russell, "The Role of Every-Day Cosmetics in Altering the Skin Microbiome: A Study Using Biodiversity," *Cosmetics* 6, no. 1 (2019): 2, https://doi.org/10.3390/cosmetics6010002.

46. C. C. Ch'ng, "Rebalancing of the Skin Microbiome With an Emollient "Plus" for Effective Management of Atopic Dermatitis: A Mini Review," *Medical Journal of Malaysia* 79, no. 2 (2024): 203–205.

47. A. Sarasati, M. H. Syahruddin, A. Nuryanti, et al., "Plant-Derived Exosome-Like Nanoparticles for Biomedical Applications and Regenerative Therapy," *Biomedicine* 11, no. 4 (2023): 1053, https://doi.org/10.3390/biomedicines11041053.

48. G. Bai, T. M. Truong, G. N. Pathak, L. Benoit, and B. Rao, "Clinical Applications of Exosomes in Cosmetic Dermatology," *Skin Health and Disease* (2024): e348, https://doi.org/10.1002/ski2.348.

49. S. O. Ghasemian, "Application of Exosomes-Derived Mesenchymal Stem Cells in Treatment of Fungal Diseases: From Basic to Clinical Sciences," *Frontiers in Fungal Biology* 2 (2021): 736093, https://doi.org/10.3389/ffunb.2021.736093.
50. M. A. Dagnelie, S. Corvec, A. Khammari, and B. Dréno, "Bacterial Extracellular Vesicles: A New Way to Decipher Host-Microbiota Communications in Inflammatory Dermatoses," *Experimental Dermatology* 29, no. 1 (2020): 22–28, https://doi.org/10.1111/exd.14050.

51. A. J. Hendricks, B. W. Mills, and V. Y. Shi, "Skin Bacterial Transplant in Atopic Dermatitis: Knowns, Unknowns and Emerging Trends," *Journal of Dermatological Science* 95, no. 2 (2019): 56–61, https://doi.org/10.1016/j.jdermsci.2019.07.001.

52. N. Natarelli, N. Gahoonia, and R. K. Sivamani, "Bacteriophages and the Microbiome in Dermatology: The Role of the Phageome and a Potential Therapeutic Strategy," *International Journal of Molecular Sciences* 24, no. 3 (2023): 2695, https://doi.org/10.3390/ijms24032695.

53. D. Özal, A. Arndt, and M. Thomé, "Bacteriophages and Related Endolysins for Reduction of Microorganisms in the Human Body – A Systematic Review," *GMS Hygiene and Infection Control* 17 (2022): Doc01, https://doi.org/10.3205/dgkh000404.

54. R. Castillo-González, I. Fernández-Delgado, and P. Comberiati, "Bacteriotherapy With Human Skin Commensals in Atopic Dermatitis," *Allergy* 77, no. 4 (2022): 1331–1333, https://doi.org/10.1111/all.15162.

55. D. A. R. Dewi, A. Perdiyana, N. M. Wiliantari, et al., "Managing the Skin Microbiome as a New Bacteriotherapy for Inflammatory Atopic Dermatitis," *Cureus* 15, no. 11 (2023): e48803, https://doi.org/10.7759/cureus.48803.

56. I. Smirnova, K. Khazhomiya, P. Ptashnikova, and O. Smirnova, "Skin Microbiome and Possibilities of Bacteriotherapy (On Example of Skin Aging and Atopic Dermatitis)," *Medical Alphabet* no. 24 (2023): 20–26, https://doi.org/10.33667/2078-5631-2023-24-20-26.

57. Y. Ito and M. Amagai, "Controlling Skin Microbiome as a New Bacteriotherapy for Inflammatory Skin Diseases," *Inflammation and Regeneration* 42, no. 1 (2022): 26, https://doi.org/10.1186/s41232-022-00212-y.

58. S. B. Park, M. Im, Y. Lee, et al., "Effect of Emollients Containing Vegetable-Derived *Lactobacillus* in the Treatment of Atopic Dermatitis Symptoms: Split-Body Clinical Trial," *Annals of Dermatology* 26, no. 2 (2014): 150–155, https://doi.org/10.5021/ad.2014.26.2.150.

59. B. Perin, A. Addetia, and X. Qin, "Transfer of Skin Microbiota Between Two Dissimilar Autologous Microenvironments: A Pilot Study," *PLoS One* 14, no. 12 (2019): e0226857, https://doi.org/10.1371/journal.pone.0226857.

60. I. A. Myles, K. W. Williams, J. D. Reckhow, et al., "Transplantation of Human Skin Microbiota in Models of Atopic Dermatitis," *JCI Insight* 1, no. 10 (2016): e86955, https://doi.org/10.1172/jci.insight.86955.

61. A. von Wright, "Regulatory Aspects of Probiotics and Other Microbial Products Intended for Skin Care," in *Skin Microbiome Handbook*, ed. N. Dayan (Hoboken, NJ: Wiley, 2020), 321–341.

62. G. L. Yingling and S. Onel, "Regulatory Agencies, Pharmaceuticals and Cosmetics," in *Kirk-Othmer Encyclopedia of Chemical Technology*, ed. Kirk-Othmer (Hoboken, NJ: John Wiley & Sons, Ltd, 2000).

63. R. Arora, R. Kaur, R. Babbar, S. Dhingra, A. K. Dhingra, and A. S. Grewal, "Evolving Advances in the Cosmetic Use of Probiotics and Postbiotics: Health, Regulatory and Marketing Aspects," *Current Pharmaceutical Biotechnology* 25 (2023): 1349–1361, https://doi.org/10.2174/1389201024666230703115732.

64. R. Hernández Medina, S. Kutuzova, K. N. Nielsen, et al., "Machine Learning and Deep Learning Applications in Microbiome Research," *ISME Communications* 2, no. 1 (2022): 98, https://doi.org/10.1038/s43705-022-00182-9.

65. G. Papoutsoglou, S. Tarazona, M. B. Lopes, et al., "Machine Learning Approaches in Microbiome Research: Challenges and Best Practices," *Frontiers in Microbiology* 14 (2023): 1261889, https://doi.org/10.3389/fmicb.2023.1261889.

66. D. Haykal, "Unleashing the Power of Biosensors and AI in Dermatology," *Aesthetic Surgery Journal Open Forum* 6 (2024): ojae030, https://doi.org/10.1093/asjof/ojae030.

67. N. Bhalla, P. Jolly, N. Formisano, and P. Estrela, "Introduction to Biosensors," *Essays in Biochemistry* 60, no. 1 (2016): 1–8, https://doi.org/10.1042/EBC20150001.

68. Y. Wang, W. Zhou, C. Shen, G. Jiang, and C. Yang, "Flexible and Printable Integrated Biosensors for Monitoring Sweat and Skin Condition," *Analytical Biochemistry* 661 (2023): 114985, https://doi.org/10.1016/j.ab.2022.114985.

69. K. Dhond, Y. Hu, and A. K. Yetisen, "Dermal Tattoo Biosensors," *Dermatologie (Heidelberg, Germany)* 74, no. 10 (2023): 819–821, https://doi.org/10.1007/s00105-023-05195-6.

70. S. L. Prescott, D. L. Larcombe, A. C. Logan, et al., "The Skin Microbiome: Impact of Modern Environments on Skin Ecology, Barrier Integrity, and Systemic Immune Programming," *World Allergy Organization Journal* 10, no. 1 (2017): 29, https://doi.org/10.1186/s40413-017-0160-5.