Advancements in skin microbiome that are redefining cosmetics

LAURICE FLOWERS1, JAIDE V.K. JENSEN2*

*Corresponding author

1. Senior Scientist II - Skin Microbiome, Arcaea, Boston, USA

2. Head of Biotechnology, Arcaea, Boston, USA

ABSTRACT:This article delves into the intricate relationship between the human microbiome and skin health, highlighting the transformative impact of emerging technologies like CRISPR-Cas systems and artificial intelligence (AI) in delivering efficacious solutions designed with the skin microbiome in mind. It explores the critical role of the skin microbiome in immune regulation, protection against pathogens, and overall health, while addressing historical and current challenges in managing skin conditions through microbiome manipulation. The convergence of new technologies promises a future of personalized solutions, tailored to individual microbiome profiles and addressing emerging consumer needs.

The Microbial Landscape of Human Skin

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“A study in healthy women providing probiotic yogurt for four weeks showed an improvement in emotional responses as measured by brain scans”

Figure 1. Skin Section with Microbiome. Most microorganisms live in the superficial layers of the stratum corneum and in the upper parts of the hair follicles. Some reside in the deeper areas of the hair follicles and are beyond the reach of ordinary disinfection procedures. There bacteria are a reservoir for recolonization after the surface bacteria are removed.

Materials and methods

Studies of major depressive disorder have been correlated with reduced Lactobacillus and Bifidobacteria and symptom severity has been correlated to changes in Firmicutes, Actinobacteria, and Bacteriodes. Gut microbiota that contain more butyrate producers have been correlated with improved quality of life (1).


A study in healthy women providing probiotic yogurt for four weeks showed an improvement in emotional responses as measured by brain scans (2). A subsequent study by Mohammadi et al. (3) investigated the impacts of probiotic yogurt and probiotic capsules over 6 weeks and found a significant improvement in depression-anxiety-stress scores in subjects taking the specific strains of probiotics contained in the yogurt or capsules. Other studies with probiotics have indicated improvements in depression scores, anxiety, postpartum depression and mood rating in an elderly population (4-7).


Other studies have indicated a benefit of probiotic supplementation in alleviating symptoms of stress. In particular, researchers have looked at stress in students as they prepared for exams, while also evaluating other health indicators such as flu and cold symptoms (1). In healthy people, there is an indication that probiotic supplementation may help to maintain memory function under conditions of acute stress.

When designing personal care products, the human element and consumer experience is paramount. A personalized and holistic approach is essential in developing new solutions with evolving needs. This review explores the research and evolution of skin microbiome focused personal care products, uniquely highlighting how brands and scientific advancements are redefining what these products can offer consumers.


Approaching the human element on the microscopic level, the human body hosts trillions of microorganisms, outnumbering human cells by a ratio of approximately 10 to 1 (1). Despite their small physical footprint, these microorganisms form complex ecosystems and play an indispensable role in human health. They are essential to the functionality of their host and aid in digestion, enhancing brain function, regulating the immune system, and perform other vital roles (2,3).


The skin microbiome represents a fascinating and highly specialized living system comprising various microorganisms, including bacteria, fungi, viruses, and archaea (4). It provides a sophisticated layer of protection, offering chemical and biological defenses against environmental damage and pathogen colonization (5). Additionally, the skin microbiome plays a vital role in immune system regulation, offering critical feedback that supports proper immune development (6).The microorganisms within the skin microbiome interact with each other and their host, forming a delicate balance that influences skin health (7).


The microbial distribution across the body is shaped by anatomical sites, with different areas offering varying levels of nutrients, moisture, and environmental exposure. For example, sebaceous regions like the forehead and back foster distinct microbial communities compared to moist areas like the underarms or dry areas like the forearms (8). These communities are also influenced by factors such as gender, age, genetics, and environment, resulting in a unique microbiome profile for every individual.


Advances in technology and research have deepened our understanding of the skin microbiome (9) where the launch of the Human Microbiome Project in 2007 represents a significant milestone. Improvements and development of new DNA sequencing technologies came with a drop in cost and accelerated skin microbiome research (10) evidenced by the increase in publications since around 2010. Importantly, there is now a strong foundation of literature describing the skin microbiome, facilitating development of cosmetics and therapeutics.


Shifting Paradigms in Skin Microorganism Research

Historically, the focus on microorganisms inhabiting the skin was largely negative, centered on the problems and diseases they could cause and less so how to support or leverage it (11). For example, the fungal species Malassezia globosa and Malassezia restricta have been implicated in dandruff, a common scalp condition that affects millions worldwide (12). Similarly, on the face and body, Cutibacterium acnes has been associated—albeit with varying degrees of accuracy (13)—with acne development, a condition that can significantly impact self-esteem and quality of life (14). Staphylococcus aureus has been associated with skin infections and atopic dermatitis (15, 16, 17). Additionally, mixed bacterial species residing in areas like the underarms and feet are known to produce body odor, often considered socially undesirable (18, 19).


Considering these concerns, it was logical to develop cosmetic solutions targeting the skin’s microbial inhabitants. The approach to addressing these issues has been to eliminate all microorganisms in the affected areas. However, despite decades of research and the use of active antimicrobial ingredients in countless formulations, consumer satisfaction with these solutions has often fallen short. Deodorants, for example, have shown mixed results in controlling body odor, with some highly effective formulations relying on harsh chemicals that may cause irritation. Similarly, antimicrobial acne treatments often provide inconsistent results, leaving individuals in an ongoing struggle to maintain clear skin.


Scientific advancements have deepened our understanding of the complex and multifaceted nature of these problems (10). For instance, rather than simply eradicating all microorganisms, some products are now targeting approaches that restore balance to the skin microbiome. This paradigm shift acknowledges the essential roles these microorganisms play and seeks to harmonize their functions rather than disrupt them entirely. By leveraging cutting-edge research, there is growing potential to develop specialized, microbiome solutions that address skin concerns more effectively while supporting overall skin health.


Among the most popular and consumer recognized strategies are prebiotics, probiotics, and postbiotics (20). These approaches leverage the interplay between microbial communities and the skin to enhance health and appearance. Prebiotics provide nutrients that support beneficial microorganisms, probiotics introduce live beneficial microbes, and postbiotics deliver beneficial byproducts of microbial metabolism. However, despite their potential, many products currently on the market fall short of delivering measurable results. A common misstep involves repurposing pre-, pro-, and postbiotic formulations designed for gut health into topical products, often without sufficient adaptation to the unique requirements of the skin microbiome. This disconnect has limited their efficacy in delivering meaningful skin benefits.


As consumer awareness of the microbiome grows, so too does the demand for scientific rigor and demonstrable efficacy in skincare solutions. Brands are rising to meet these expectations, bringing more sophisticated and effective microbiome targeted products to market. The breadth of possibilities in microbiome research is enormous, with exciting discoveries beginning to reshape the industry. For example, specific species of Staphylococcus have been found to increase production of ceramide—lipid molecules critical for maintaining the skin barrier and preventing moisture loss (21). By formulating products with precursors that encourage ceramide production, skincare companies can amplify this benefit, delivering improvements in skin hydration and resilience.


Precision Skin Microbiome Solutions: Current and Future Potential

Recently, commercial products utilizing precision prebiotics have entered the market. One example is the brand Rulo Skin, which features a prebiotic blend that promotes production of long-chain ceramides on the skin by skin commensals. Precision prebiotics are also being used to selectively support the growth of beneficial microbial species while suppressing those responsible for undesirable effects. Arcaea has developed innovative prebiotics formulations with two distinct applications delivering tangible consumer outcomes. The first modulates armpit microbiomes to shift from an odorous underarm state to a non-odorous state. The second prebiotic blend was designed to rebalance the scalp microbiome, with the ability to modulate scalp microbiome types on scalps with flakes and/or redness to significantly reduced or eliminated, promoting scalp microbiome compositions that are associated with scalp health (22).


The use of probiotics for improving skin conditions has been explored for over two decades, with more advancements for the use in cosmetics over the past decade. A probiotic C. acnes strain for cosmetic use was developed by S-Biomedic that produces the protein RoxP with antioxidant activity for improved skin health (23). Though not yet developed as a probiotic, researchers have isolated the bacterium Pantoea eucrina from high-altitude Tibetans with the proposed ability to protect the skin through DNA repair (24). Such bacterial strain could be interesting as a probiotic to be used in sunscreens to provide protection from the harmful UVB and UVA rays of the sun.


Though some probiotics in skincare may provide benefits without colonization of the skin, for applications where skin engraftment is desired an investment in research to ensure it is required. Various factors have been demonstrated to impact engraftment including interspecies antagonism (25), metabolic niche (26), and immune response (27). Additionally, new research has demonstrated that probiotic application of select skin commensals and other strains on abrased skin increased inflammation and delayed barrier repair (28). This is an important consideration when developing and testing probiotics for use on skin that has an impaired barrier.


In another exciting area of research, phage therapy is being developed to address bacterial strains implicated in acne (29). Unlike broad spectrum antimicrobials that indiscriminately kill bacteria, phage cocktails target only the specific bacteria causing the issue, such as Cutibacterium acnes, while preserving the broader microbiome balance (29). Commercially available products containing phage cocktails addressing inflammaging and redness have been developed by Parallel Health.


Despite the promise of microbiome based solutions, they are not without challenges. The skin microbiome is unique to each individual, as a result, the effectiveness of these solutions often depends on the presence of specific microbial species within an individual’s microbiome (30). For example, products designed to enhance ceramide production require the presence of the bacteria that increase ceramide production to be effective, while phage-based acne treatments depend on the presence of specific bacterial strains as targets.


The inherent variability of the skin microbiome highlights the need for further research and broader datasets to refine and expand these solutions. Current advancements have largely relied on data from limited populations, and as microbiome studies become more feasible and widespread, the resulting diversity of data will allow for greater personalization and efficacy. The ability to tailor products to specific microbiome profiles holds immense potential, but this requires significant investment in understanding microbial diversity across global populations-work that is currently underway (31).


Emerging Technologies and their Application

Around 2012 the use of the CRISPR-Cas system for genome editing was established (32). This was a true breakthrough innovation with powerful applications. The technology also holds promise for its ability to precisely control the microbiome in situ (33). This can be achieved in a multitude of ways including by targeted killing of microbial species or even subspecies serving as a potential alternative to antibiotics, it can be used to remove genes with undesired effects such as genes encoding enzymes responsible for converting sweat molecules to odorous molecules, add genes that will give select microorganisms the ability to produce new molecules such as antioxidants that are of benefit to the skin, or manipulate gene expression resulting in a modulation of metabolite and protein production (34). As an example Eligo Bioscience has used their CRISPR-Cas system (35) to target and eliminate exclusively the C. acnes strains that contain disease associated genes, playing a key role in moderate to severe acne, while preserving the C. acnes strains that are crucial for skin health.


While leveraging CRISPR-based microbiome editing can allow truly life altering results for patients and consumers, it remains an emerging field. Depending on the desired edit(s) and target strain(s) research may be required to understand the DNA repair mechanisms of the target strains to achieve the desired edits, DNA delivery into the target strains, and achieving sufficient editing efficiency are additional potential challenges (33, 36). Moreover, as our understanding of the complex microbiome ecosystem is still limited, effects within the microbial communities as well as with the host immune system can be hard to predict (33). Lastly, regulatory frameworks and safety protocols are under development. They are important for avoiding unintended ecological and health repercussions.


Another new powerful technology, artificial intelligence (AI), promises to accelerate progress in the skin microbiome field. AI-driven analyses can rapidly process complex datasets, identify patterns, and predict interactions within the microbiome, enabling the development of precision-targeted solutions at an unprecedented scale. For instance, AI could advance our knowledge of the microbiome's role in skin health, identify novel molecules with beneficial properties, identify and support the design of efficient probiotics, optimize CRISPR and phage therapies, or design prebiotic formulations that precisely modulate microbial metabolism. The quantity and quality of whole genome sequencing data along with metadata is important for enabling AI-driven product development resulting in high performance and reducing product development timelines. Providing AI models with outcomes of human studies conducted to test products developed with its assistance will further increase its predictive power.


There are many examples of how AI is being used to advance skin microbiome research and drive new product development. For example, AI has been used to successfully predict age, skin hydration, menopausal status and smoking status from study participants' leg skin microbiome (37). A model named SkinBug was developed to predict the metabolism of any molecule by the skin microbiome. This type of model could for instance be used to develop novel prebiotics and postbiotics or to gain an understanding of how exposure to pollutants or topicals may impact the skin microbiome and skin health (38). Some companies offering skin microbiome sequencing services are leveraging AI to profile microbiome diversity, discover disease biomarkers, analyze microbiome-host interactions, evaluate the impact of cosmetic products, create suggestions for skin care routines for consumers, and develop targeted cosmetics or therapeutics. These computational approaches facilitate personalized skincare strategies, optimize product formulations, and enable predictive longitudinal monitoring of skin health.


Conclusion

As our knowledge of the skin microbiome continues to expand, we believe there are opportunities to create powerful solutions that address emerging needs, including consumers increasingly affected by climate change that can result in skin issues (39,40,41) as well as consumers experiencing peri- and menopause which historically have been neglected by the scientific community, healthcare providers, and the personal care industry.


Critical knowledge gaps still exist in understanding complex interactions between microorganisms, immune systems, and broader physiological systems, including emerging research on the 'skin-gut' and 'skin-brain' axes. Further, characterization of underexplored microbiome components like viruses, bacteriophages, and archaea may yield discoveries that can be harnessed for future products (42). One barrier for these studies is the need for advancement in sequencing technology for cost and accuracy. Expanding global diversity in microbiome research, establishing long-term longitudinal studies, and fostering interdisciplinary collaboration will be essential to translate technological capabilities into effective, personalized skin health solutions.


The future of microbiome targeted personal care topicals is undeniably exciting. With the convergence of advanced technologies and growing consumer demand, the field is primed to revolutionize how we understand and care for the skin. By embracing these innovations, we move closer to unlocking the full potential of the microbiome and achieving truly personalized and effective skincare.


Conclusion

The future of cosmetics lies in the continued evolution of holistic approaches which represents a transformative shift in the industry, merging scientific advancements, natural ingredients, and wellness principles. By understanding and embracing the interconnectedness of these elements, the cosmetics industry can cultivate products that not only enhance external beauty but also contribute to the overall well-being of individuals and the planet.


The interplay between beauty from within and topical cosmetics is the key for future products. The integration of biotechnology and green chemistry is revolutionizing cosmetic formulations, offering sustainable and biocompatible alternatives.


Developers can implement blockchain to trace the journey of ingredients from source to product. Nevertheless, the efficacy of the natural products should be scientifically proven. Marketers can communicate transparency as a brand value, and parallelly educate consumers by highlighting how specific ingredients contribute to radiant and healthy skin.


By embracing the synergy between these approaches and leveraging scientific advancements, the cosmetics industry can provide consumers with comprehensive beauty solutions that cater to both internal and external dimensions of beauty.

Surfactant Applications

The application area lends itself particularly well to the use of AI. Active today in this area is the US company Potion AI (6). The company provides AI-powered formulation tools for beauty and personal care R&D. Their offerings include Potion GPT, next generation ingredient and formula databases and AI document processing. Potion’s work could have a significant impact on the entire surfactant value chain, from raw material suppliers to end consumers. By using their GPT technology, they can help target work toward novel surfactant molecules that have optimal properties for specific applications. By using their ingredient and formula databases, they can access and analyze a vast amount of data on surfactant performance, safety, and sustainability. By using their AI document processing, they can extract and organize relevant information from patents, scientific papers, and regulatory documents. These capabilities could enable Potion AI's customers to design and optimize surfactant formulations that are more effective, eco-friendly, and cost-efficient. A particularly interesting application for this type of capability is deformulation.


Deformulation is the process of reverse engineering a product's formulation by identifying and quantifying its ingredients. Deformulation can be used for various purposes, such as quality control, competitive analysis, patent infringement, or product improvement. However, deformulation can be challenging, time-consuming, and costly, as it requires sophisticated analytical techniques, expert knowledge, and access to large databases of ingredients and formulas.


AI can potentially enhance and simplify the deformulation process by using data-driven methods to infer the composition and structure of a product from its properties and performance. For example, AI can use machine learning to learn the relationships between ingredients and their effects on the product's characteristics, such as color, texture, fragrance, stability, or efficacy. AI can also use natural language processing to extract and analyze information from various sources, such as labels, patents, literature, or online reviews, to identify the possible ingredients and their concentrations in a product.


Figure 2. Skin Section with Microbiome. Most microorganisms live in the superficial layers of the stratum corneum and in the upper parts of the hair follicles. Some reside in the deeper areas of the hair follicles and are beyond the reach of ordinary disinfection procedures. There bacteria are a reservoir for recolonization after the surface bacteria are removed.

About the Author

JAIDE JENSEN

Jaide works at the intersection of biotech and beauty, translating biological concepts to products. She has a passion for leveraging biological systems to solve today's challenges by delivering on functionality, efficacy, and sustainability. Prior to her role at Arcaea she worked at the biotech company Ginkgo Bioworks, designing microorganisms for production of industrially relevant compounds and later transitioned into business development. Jaide gained her expertise in metabolic engineering and synthetic biology from the Technical University of Denmark, Bielefeld University, and MIT.

JAIDE JENSEN

Head of Biotechnology, Arcaea, Boston, USA

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