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Often colloquially termed "fungal acne," Malassezia folliculitis (MF) is an infection of the hair follicle triggered by yeasts belonging to the Malassezia genus (formerly known as Pityrosporum). While these lipophilic yeasts are typically part of the natural skin microbiome, under specific conditions, they can become pathogenic causing acne-like symptoms. What We Know: Following birth, Malassezia typically establishes residence on the skin and is usually well-tolerated by the immune system. However, its pathogenic capabilities emerge when it infiltrates the stratum corneum under conducive conditions, such as hot and humid climates, engaging directly with the host immune system and via chemical mediators (Saunte, Gaitanis & Hay, 2020). Essentially, the transformation of Malassezia from commensal to pathogenic is driven by a complex interaction between the host and the fungus, resulting in the production of virulence factors such as indoles, reactive oxygen species, azelaic acid, hyphae formation and biofilm formation (Kurniadi, Hendra Wijaya & Timotius, 2022). The primary species linked to MF include M. furfur, M. globosa, M. restricta, M. sympodialis and M. pachydermatis (Henning et al., 2023). These species penetrate the pilo-sebaceous unit, resulting in follicular dilation and the accumulation of Malassezia cells. If follicular walls rupture, it triggers an inflammatory response. This can be misdiagnosed as acne, steroid acne, bacterial folliculitis, eosinophilic folliculitis, pustular drug eruptions or lymphomatoid papulosis (Saunte, Gaitanis & Hay, 2020). Industry Impact and Potential: While systemic antifungal monotherapy typically yields better results, topical therapy is useful in conjunction and is beneficial in situations where systemic treatment is not feasible. Topical antifungals, tretinoin, benzoyl peroxide azoles, selenium sulphide, and propylene glycol are viable topical options for managing MF (Saunte, Gaitanis & Hay, 2020). Currently, there is no internationally approved treatment guideline for managing MF. This presents an exciting opportunity to explore microbiome-focused treatment approaches, tailoring therapies to restore microbial balance and target Malassezia overgrowth effectively (Saunte, Gaitanis & Hay, 2020). Our Solution: With a vast database of over 20,000 microbiome samples and 4,000 ingredients, Sequential offers comprehensive services to tackle issues like MF. Our customisable microbiome studies and product formulation support ensure effective product development. References: Henning, M. a. S., Hay, R., Rodriguez-Cerdeira, C., Szepietowski, J.C., Piraccini, B.M., et al. (2023) Position statement: Recommendations on the diagnosis and treatment of Malassezia folliculitis. Journal of the European Academy of Dermatology and Venereology. 37 (7), 1268–1275. doi:10.1111/jdv.18982. Kurniadi, I., Hendra Wijaya, W. & Timotius, K.H. (2022) Malassezia virulence factors and their role in dermatological disorders. Acta Dermatovenerologica Alpina, Pannonica, Et Adriatica. 31 (2), 65–70. Saunte, D.M.L., Gaitanis, G. & Hay, R.J. (2020) Malassezia-Associated Skin Diseases, the Use of Diagnostics and Treatment. Frontiers in Cellular and Infection Microbiology. 10, 112. doi:10.3389/fcimb.2020.00112.

While our understanding of the microbial composition of the vulva is still evolving, it holds the potential to maintain overall genital health. Investigating how feminine hygiene products affect the vulvar microbiome is crucial for understanding and improving women's health and intimate care practices. What We Know: The vulvar microbiome displays significant diversity both within individuals and among different women, with current research having found no single species universally present (Graziottin, 2024). While opinions vary among professionals regarding the necessity of feminine care products, in instances where they are deemed beneficial, certain ingredients can offer greater advantages to the vulvar microbiome than others. Thymol, a component of thyme oil, has gained attention in feminine hygiene products for its antimicrobial and antifungal properties, effectively maintaining the beneficial microbiota. It inhibits the growth of pathogenic microbes like Candida albicans and Gardnerella vaginalis, while also possessing anti-inflammatory properties (Braga et al., 2008). The inclusion of lactic acid in feminine hygiene products helps to support the vulvar microbiome by maintaining an acidic pH (Graziottin, 2024). To manage odours, feminine washes may contain ketoglutaric acid, which is an antioxidant. These properties have the potential to oxidise amines linked to malodor, thereby providing anti-odour benefits (Graziottin, 2024). Industry Impact & Potential: Researchers have developed a cleansing wash containing thymol and an acidic pH, along with glycerin, ketoglutaric acid, and lactic acid, which has shown promise in reducing pH levels and discomfort in pregnant and postpartum women with vulvar and vaginal issues. Compared to alternative lactic acid-based washes, it better preserves skin hydration (Murina et al., 2020). Despite advancements like this, the market remains underexplored, offering opportunities for the exploration and development of microbiome-friendly products in the realm of feminine hygiene. Our Solution: In addition to vulvar microbiome analysis, we at Sequential provide services for assessing skin, scalp and oral microbiomes, and have established our company as a leader in facilitating the development of microbiome-friendly products. Our team of experts is well-equipped to support your company in formulating innovative products suitable for maintaining and improving the vulvar microbiome to support women’s health. Reference List: Braga, P.C., Culici, M., Alfieri, M. & Dal Sasso, M. (2008) Thymol inhibits Candida albicans biofilm formation and mature biofilm. International Journal of Antimicrobial Agents. 31 (5), 472–477. doi:10.1016/j.ijantimicag.2007.12.013. Graziottin, A. (2024) Maintaining vulvar, vaginal and perineal health: Clinical considerations. Women’s Health (London, England). 20, 17455057231223716. doi:10.1177/17455057231223716. Murina, F., Caimi, C., Felice, R., Di Francesco, S. & Cetin, I. (2020) Characterization of female intimate hygiene practices and vulvar health: A randomized double-blind controlled trial. Journal of Cosmetic Dermatology. 19 (10), 2721–2726. doi:10.1111/jocd.13402.

Rosacea, a chronic inflammatory skin condition, involves complex interactions between the skin microbiota and host conditions. While the exact pathophysiology is not clearly understood, research has implicated various microorganisms. What We Know: Demodex mites (generally found at the base of eyelashes) have been associated with rosacea, with higher densities found in affected individuals. Although typically harmless in small numbers, D. folliculorum and D. brevis may stimulate inflammatory pathways and compromise the skin barrier, contributing to the condition. While their exact role in rosacea remains unclear, treatments targeting Demodex have shown potential (Sánchez-Pellicer et al., 2024). Bacillus oleronius (Heyndrickxia oleronia), a bacterium originally isolated from Demodex, has been shown to exacerbate inflammation in rosacea patients. Furthermore, elevated skin temperature characteristic of rosacea patients altered the growth and protein profile of B. oleronius, resulting in increased production of its immunoreactive proteins. However, studies on rosacea have shown its presence in affected skin samples to be inconsistent (Maher, Staunton & Kavanagh, 2018). Corynebacterium kroppenstedtii, found in mutualistic symbiosis with D. folliculorumhas, has been linked to rosacea, particularly in subjects between 40 and 49 years of age. Research suggests that effective antibiotic treatment against this bacterium could potentially improve rosacea symptom management (Rainer et al., 2020). Staphylococcus epidermidis, a typically beneficial bacterium, may exhibit virulence factors in rosacea patients, contributing to the disease's pathogenesis (Sánchez-Pellicer et al., 2024). Industry Impact & Potential: Systemic antibiotics have been effective in managing rosacea. However, their specific impact on the cutaneous microbiota and bacteria related to rosacea pathophysiology requires further study (Sánchez-Pellicer et al., 2024). In addition, while the microbiological aspects of rosacea provide insights into its pathogenesis, further research is needed to elucidate the exact roles of various microorganisms and develop targeted treatments (Sánchez-Pellicer et al., 2024). Studies suggest that topical probiotics can positively impact skin health by influencing the skin microbiota and immune response. While their effectiveness for rosacea is not fully understood, probiotics may enhance skin barrier function, reduce inflammation and restore balance to the skin microbiome, making them a promising avenue for symptom management and potential treatment (Sánchez-Pellicer et al., 2024). Our Solution: Sequential offers a unique end-to-end Microbiome Testing solution that may be applied to the case of rosacea. Get in touch to collaborate with our experts to investigate topical microbiome-focused approaches to treating skin concerns and conditions, like rosacea. Reference List: Maher, A., Staunton, K. & Kavanagh, K. (2018) Analysis of the effect of temperature on protein abundance in Demodex-associated Bacillus oleronius. Pathogens and Disease. 76 (4), fty032. doi:10.1093/femspd/fty032. Rainer, B.M., Thompson, K.G., Antonescu, C., Florea, L., Mongodin, E.F., Bui, J., Fischer, A.H., Pasieka, H.B., Garza, L.A., Kang, S. & Chien, A.L. (2020) Characterization and Analysis of the Skin Microbiota in Rosacea: A Case–Control Study. American Journal of Clinical Dermatology. 21 (1), 139–147. doi:10.1007/s40257-019-00471-5. Sánchez-Pellicer, P., Eguren-Michelena, C., García-Gavín, J., Llamas-Velasco, M., Navarro-Moratalla, L., Núñez-Delegido, E., Agüera-Santos, J. & Navarro-López, V. (2024) Rosacea, microbiome and probiotics: the gut-skin axis. Frontiers in Microbiology. 14. doi:10.3389/fmicb.2023.1323644.

Many consumers use skincare products with the intention of achieving various aesthetic goals, without realising their potential impact on the skin's microbiome. Factors like ingredients and formulations can disrupt this balance, highlighting the importance of understanding how skin care choices affect skin health What We Know: Cosmetic skincare products can influence the composition and diversity of the skin's microbial community. Ingredients like carbohydrates, proteins and lipids can promote the growth of specific skin bacteria. For example, the lipid components found in moisturisers can serve as nutrients, fostering the growth of lipophilic bacteria like Staphylococcus epidermidis and Cutibacterium acnes (Skowron et al., 2021). Furthermore, emulsifiers or preservatives, such as parabens, methylisothiazolinone have the potential to disturb microbial balance by suppressing the growth of beneficial bacteria like S. epidermidis, potentially leading to dysbiosis (Fournière et al., 2020). The impact of preservatives on the skin microbiome has been debated due to their necessity to prevent contamination, but simultaneous potentially negative effects on microbiome diversity. However, more recent research established that their impact depends on factors like concentration, exposure duration and individual skin resilience (Murphy et al., 2021). Industry Impact & Potential: Research into skin microbiota and ingredients optimising skin microbiota is essential for cosmetic companies creating new cosmetic products. Initiatives and certifications to ensure that cosmetic products are free from contaminants, harmless to specific bacteria and non-disruptive to the skin's natural microbiome equilibrium are becoming more prominent in the skincare industry (Han & Kim, 2024). Skincare brands have and continue to formulate products including microbiome beneficial ingredients, like pre- and postbiotics. These include Aveeno’s CALM+RESTORE® range (with oatmeal, which contains prebiotic carbohydrate beta-glucans), Lancome’s Genifique products (containing Bifida ferment lysate, Lactobacillus ferment, postbiotic yeast extract and prebiotic alpha glucan oligosaccharide) as well as Lactoclear’s postbiotic products (containing Enterococcus Faecalis ferment) among many others (Han & Kim, 2024). Our Solution: With an extensive database comprising over 20,000 microbiome samples and 4,000 ingredients, alongside a global network of more than 10,000 testing participants, Sequential delivers thorough services for assessing product impacts and formulations. Our customisable microbiome studies offer real-world testing scenarios, while our formulation support guarantees the preservation of biome integrity in products. Thus, we stand as the optimal partner to leverage our solutions for your product development and efficacy needs. Reference List: Fournière, M., Latire, T., Souak, D., Feuilloley, M.G.J. & Bedoux, G. (2020) Staphylococcus epidermidis and Cutibacterium acnes: Two Major Sentinels of Skin Microbiota and the Influence of Cosmetics. Microorganisms. 8 (11), 1752. doi:10.3390/microorganisms8111752. Han, J.H. & Kim, H.S. (2024) Skin Deep: The Potential of Microbiome Cosmetics. Journal of Microbiology (Seoul, Korea). doi:10.1007/s12275-024-00128-x. Murphy, B., Hoptroff, M., Arnold, D., Eccles, R. & Campbell-Lee, S. (2021) In-vivo impact of common cosmetic preservative systems in full formulation on the skin microbiome. PLOS ONE. 16 (7), e0254172. doi:10.1371/journal.pone.0254172. Skowron, K., Bauza-Kaszewska, J., Kraszewska, Z., Wiktorczyk-Kapischke, N., Grudlewska-Buda, K., Kwiecińska-Piróg, J., Wałecka-Zacharska, E., Radtke, L. & Gospodarek-Komkowska, E. (2021) Human Skin Microbiome: Impact of Intrinsic and Extrinsic Factors on Skin Microbiota. Microorganisms. 9 (3), 543. doi:10.3390/microorganisms9030543.

Vitamin A and its derivatives have become essential components of mainstream skincare products, popular for their anti-aging and anti-acne benefits. Yet, as we probe further into their effects on skin well-being, their interplay with the skin microbiome emerges as an avenue for exploration, extending beyond their established properties and into new realms of understanding and application. What We Know: Vitamin A deficiency has been associated with skin infection. However, the mechanism of how vitamin A provides skin immunity is not yet well understood (Harris et al., 2019). Human skin cells naturally produce Resistin protein, while in mice, epidermal keratinocytes and sebocytes produce a similar molecule known as Resistin-like molecule α (RELMα). Research showed that when activated by the vitamin A analog isotretinoin, RELMα exhibited antimicrobial properties. This effectively prevented skin infections and may suggest a similar property of Resistin activated by vitamin A in humans (Harris et al., 2019). When administered as a 0.025% cream for topical acne treatment, retinoic acid, a potent derivative of vitamin A, demonstrated notable results for individuals with mild acne vulgaris. Following one month of use, it exhibited efficacy in reducing bacterial diversity, reshaping microbiota composition and notably decreasing Cutibacterium acnes while elevating Staphylococcus epidermidis relative abundance (Wongtada et al., 2023). Industry Impact & Potential: Vitamin A and its derivatives have immunomodulatory properties that offer protection against fungal infections caused by Candida albicans, Aspergillus spp. and Microsporum spp. This suggests that investigating vitamin A derivatives such as retinoids in clinical settings could offer a promising therapeutic approach for treating fungal infections (Joshi et al., 2023). Understanding the role of vitamin A and its derivatives on both the innate immune system and the skin microbiome is crucial for advancing translational skin biology research and devising effective therapeutic approaches (Roche & Harris, 2021). Specifically, this can provide insight on disease progression and treatment responses, particularly regarding therapies targeting innate immune signalling and antimicrobial peptide production (Roche & Harris, 2021). Our Solution: At Sequential, we specialise in comprehensive Microbiome Product Testing, which is customisable to align with your unique product development and formulation goals. With our expert guidance and tailored services, we empower businesses to pioneer innovative strategies for topical solutions, such as creating microbiome-friendly products containing vitamin A and its derivatives, ensuring efficacy and compatibility for healthier skin. Reference List: Harris, T.A., Gattu, S., Propheter, D.C., Kuang, Z., Bel, S., Ruhn, K.A., Chara, A.L., Edwards, M., Zhang, C., Jo, J.-H., Raj, P., Zouboulis, C.C., Kong, H.H., Segre, J.A. & Hooper, L.V. (2019) Resistin-like Molecule α Provides Vitamin-A-Dependent Antimicrobial Protection in the Skin. Cell Host & Microbe. 25 (6), 777-788.e8. doi:10.1016/j.chom.2019.04.004. Joshi, M., Hiremath, P., John, J., Ranadive, N., Nandakumar, K. & Mudgal, J. (2023) Modulatory role of vitamins A, B3, C, D, and E on skin health, immunity, microbiome, and diseases. Pharmacological Reports. 75 (5), 1096–1114. doi:10.1007/s43440-023-00520-1. Roche, F. & Harris, T. (2021) Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative Review. Nutrients. 13 (2). doi:10.3390/nu13020302. Wongtada, C., Prombutara, P., Asawanonda, P., Noppakun, N., Kumtornrut, C. & Chatsuwan, T. (2023) Distinct skin microbiome modulation following different topical acne treatments in mild acne vulgaris patients: A randomized, investigator-blinded exploratory study. Experimental Dermatology. 32 (6), 906–914. doi:10.1111/exd.14779.

Multiple factors are responsible for the makeup of the skin microbiome of an individual, including host genetics, age, hygiene practices, diet, nutrition, lifestyle, topical treatments and the environment. Research suggests that where we live can profoundly influence the microbial composition and overall health of our microbiomes. What We Know: Facial skin is impacted by external factors like climate, temperature, humidity, UV exposure and pollution, as it is more exposed to the environment compared to other skin (Proksch, 2008). Research that investigated the facial microbiome and metabolome across different geographic regions concluded that there were significant alterations in the abundance of multiple microorganisms between individuals (Tao et al., 2024). In a study across various regions in China, those residing in the northwest (in high altitude and dry climate) exhibited lower levels of Malassezia and bacterial diversity, as well as reduced total lipid content. However, they showed elevated levels of ceramides and fatty acids compared to individuals in southern regions (warm and wet climates) (Tao et al., 2024). Skin bacteria thrive in warm temperatures (33.2–35.0°C) with lipid-dependent organisms like Malassezia and Cutibacterium flourishing in such environments due to increased sebum secretion (Grice & Segre, 2011). Research also demonstrated that subjects living in rural areas exhibited significantly greater intra group variation in microbial community structure compared to urban subjects (Ying et al., 2015). Variations in bacterial populations across regions may be influenced by factors like humidity, UV exposure and temperature fluctuations. Higher humidity levels support greater bacterial diversity, while UV exposure alters the skin microbiome (Tao et al., 2024) Industry Impact and Potential: By analysing these aspects across geography, we can uncover climate-related influences on skin disorders, enabling tailored skincare recommendations for diverse regions (Tao et al., 2024). Increasing urbanisation correlates with higher levels of potentially pathogenic  bacteria and fungi, which may explain the urban prevalence of skin diseases like acne and atopic dermatitis. This highlights the need for urban-specific skincare, creating opportunities for specialised products and research (McCall et al., 2020). However, further research is necessary to fully elucidate the effects of environmental factors on the microbiome (Tao et al., 2024) Our Solution: Exploring environmental influence on the microbiome is a promising avenue for personalised skincare tailored to the individual needs of people globally. With three testing centres in distinct climates (New York, London and Singapore) Sequential offers comprehensive Microbiome Testing and guidance in product development and formulation, providing a toolkit for your company to delve into personalised skincare that considers our uniqueness. References: Grice, E.A. & Segre, J.A. (2011) The skin microbiome. Nature Reviews Microbiology. 9 (4), 244–253. doi:10.1038/nrmicro2537. McCall, L.-I., Callewaert, C., Zhu, Q., Song, S.J., Bouslimani, A., et al. (2020) Home chemical and microbial transitions across urbanization. Nature Microbiology. 5 (1), 108–115. doi:10.1038/s41564-019-0593-4. Proksch, E. (2008) Protection Against Dryness of Facial Skin: A Rational Approach. Skin Pharmacology and Physiology. 22 (1), 3–7. doi:10.1159/000159771. Tao, R., Li, T., Wang, Y., Wang, R., Li, R., Bianchi, P., Duplan, H., Zhang, Y., Li, H. & Wang, R. (2024) The facial microbiome and metabolome across different geographic regions. Microbiology Spectrum. 12 (1), e03248-23. doi:10.1128/spectrum.03248-23. Ying, S., Zeng, D.-N., Chi, L., Tan, Y., Galzote, C., Cardona, C., Lax, S., Gilbert, J. & Quan, Z.-X. (2015) The Influence of Age and Gender on Skin-Associated Microbial Communities in Urban and Rural Human Populations. PLOS ONE. 10 (10), e0141842. doi:10.1371/journal.pone.0141842.

Acne is a prevalent and multifactorial skin disease affecting teenagers and adults, generally stemming from an imbalance in the skin microbiome. Studies have shown that various essential oils (EOs) possess antimicrobial properties that can inhibit the growth of acne-causing bacteria strains like Cutibacterium acnes and Staphylococcus epidermidis. What We Know: Current acne treatments often involve topical or oral antibiotics, raising concerns about antibiotic resistance in C. acnes strains (Sardana et al., 2015). EOs are natural, concentrated liquids derived from plants, known for their aromatic properties and diverse biological characteristics, including bactericidal, virucidal and fungicidal properties (Cossetin et al., 2021). These include oregano, lavender, lemon grass, myrtle, lemon, thyme, eucalyptus, rosemary and tea tree EOs, which have all demonstrated anti-inflammatory, antioxidant and antimicrobial properties (Bungau et al., 2023). EOs are able to permeate the skin and facilitate the enhanced penetration of active compounds into deeper skin layers (Bungau et al., 2023). Their antimicrobial property occurs as their bioactive components target multiple cellular sites and interact with cell membranes, disrupting microbial integrity and ultimately causing cell death (Bungau et al., 2023). Industry Impact & Potential: Incorporating English lavender and peppermint EOs into gelatine nanofibers created effective topical patches for localised acne treatment by diminishing C. acnes and S. epidermidis (Uhlířová et al., 2023). Therefore, English lavender and peppermint EOs may be beneficial in the gentle and focused treatment of acne, as well as potentially other microbial-related skin conditions (Uhlířová et al., 2023). However, a challenge with EO use is their standardisation, which arises due to different cultivation conditions that produce EOs of varied quality, quantity and composition (Uhlířová et al., 2023). Methods for assessing antioxidant potential, such as determining total phenolic content, evaluating reducing power, measuring ferrous ion chelating activity, among other methods, are vital for gauging the efficacy and safety of essential oil use in acne treatment (Bungau et al., 2023). Future investigations could focus on developing innovative acne treatments incorporating essential oils and evaluating their effectiveness through large-scale clinical trials. Moreover, further research is warranted to elucidate the mechanisms of action of essential oils and identify their optimal doses and safety profiles for effective management of acne vulgaris (Bungau et al., 2023). Our Solution: At Sequential, we offer a comprehensive Microbiome Product Testing Solution, separately or in conjunction with guided product development and formulation services. This holistic approach enables your business to explore innovative methods for addressing skin conditions, like acne, using essential oils treatment strategies. Reference List: Bungau, A. F., Radu, A. F., Bungau, S. G., Vesa, C. M., Tit, D. M., Purza, A. L., & Endres, L. M. (2023). Emerging Insights into the Applicability of Essential Oils in the Management of Acne Vulgaris. Molecules (Basel, Switzerland) , 28(17), 6395. https://doi.org/10.3390/molecules28176395 Castellanos Lorduy, H. J., Pérez Cely, H. C., Casadiego Rincón, E. J., Henao Riveros, S. C., & Colorado, C. L. (2021). Cutibacterium acnes tetracycline resistance profile in patients with acne vulgaris, in a colombian dermatologic center. Actas Dermo-Sifiliográficas (English Edition), 112(10), 873-880. doi:10.1016/j.adengl.2021.09.003 Cossetin, L. F., Garlet, Q. I., Velho, M. C., Gündel, S., Ourique, A. F., Heinzmann, B. M., & Monteiro, S. G. (2021). Development of nanoemulsions containing lavandula dentata or myristica fragrans essential oils: Influence of temperature and storage period on physical-chemical properties and chemical stability. Industrial Crops and Products, 160, 113115. doi:10.1016/j.indcrop.2020.113115 Sardana, K., Gupta, T., Garg, V.,K., & Ghunawat, S. (2015). Antibiotic resistance to propionobacterium acnes: Worldwide scenario, diagnosis and management. Expert Review of Anti-Infective Therapy, 13(7), 883-896. doi:10.1586/14787210.2015.1040765 Uhlířová, R., Langová, D., Bendová, A., Gross, M., Skoumalová, P., & Márová, I. (2023). Antimicrobial Activity of Gelatin Nanofibers Enriched by Essential Oils against Cutibacterium acnes and Staphylococcus epidermidis. Nanomaterials (Basel, Switzerland), 13(5), 844. https://doi.org/10.3390/nano13050844

Elucidating the relationship between ceramides and the skin microbiome could revolutionise the treatment of skin disease. Ceramides, the lipid molecules abundant in the stratum corneum, play a crucial role in skin barrier function and alterations to their levels or profiles are associated with impaired barrier function and, in some cases, skin disease. What We Know: Ceramides are responsible for preventing water loss, maintaining skin moisture levels and ultimately maintaining skin barrier function (Baker et al., 2023). The breakdown of the skin barrier is a common feature of numerous inflammatory skin conditions and is well-understood in diseases like atopic dermatitis (AD) and psoriasis (Rajkumara et al., 2023). In the case of AD, patients generally have reduced ceramide levels (Elias et al., 2019). Regarding psoriasis, there is a reduction in the enzymes involved in ceramide biosynthesis and metabolism, causing a decrease in overall ceramides levels (Choi & Maibach, 2005). Staphylococcus epidermidis plays a role in skin barrier maintenance by secreting sphingomyelinase, an enzyme that facilitates the conversion of host cell sphingomyelin into ceramides (Zheng et al., 2022). Ceramides also play a role in maintaining the acidic mantle: a protective film that covers that surface of the skin with a pH 4.5-5.5, which is crucial for the proliferation of beneficial microorganisms like S. epidermidis (Baker et al., 2023). Industry Impact & Potential: Probiotic-type topical treatments, containing microbiota like S. epidermidis, show potential in treating skin diseases by leveraging their role in maintaining skin barrier integrity (Zheng et al., 2022). Researchers propose a targeted approach of screening the existing skin microbiome composition for deficiencies in S. epidermidis enzymes and subsequently treating the skin with strains that produce the lacking enzyme(s) in combination with direct bacterial interference mechanisms to eliminate harmful pathogens (Zheng et al., 2022). pH-optimised moisturisers enhance the chemical skin barrier by promoting optimal enzymatic activity that boosts ceramide synthesis, as well as creating favourable environments for beneficial microorganisms (Rajkumara et al., 2023). Mice models have shown that through the bacterial phenomenon of quorum sensing, commensal microbiota can inhibit Staphylococcus aureus toxin production (which is highly associated with AD symptoms), thus preventing skin barrier damage and inflammation (Williams et al., 2019). Our Solution: Sequential offers an end-to-end Microbiome Product Testing Solution, alongside guided product development and formulation services. Leveraging our expertise, we assist businesses in devising novel approaches to topical ceramide and/or probiotic-based treatments for various skin diseases and inflammatory conditions. Reference List: Baker, P., Huang, C., Radi, R., Moll, S. B., Jules, E., & Arbiser, J. L. (2023). Skin Barrier Function: The Interplay of Physical, Chemical, and Immunologic Properties. Cells, 12(23), 2745. https://doi.org/10.3390/cells12232745 Bouwstra, J. A., Helder, R. W. J., & El Ghalbzouri, A. (2021). Human skin equivalents: Impaired barrier function in relation to the lipid and protein properties of the stratum corneum. Advanced drug delivery reviews, 175, 113802. https://doi.org/10.1016/j.addr.2021.05.012 Choi, M. J., & Maibach, H. I. (2005). Role of ceramides in barrier function of healthy and diseased skin. American journal of clinical dermatology, 6(4), 215–223. https://doi.org/10.2165/00128071-200506040-00002 Elias, P. M., Wakefield, J. S., & Man, M. Q. (2019). Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis. Skin pharmacology and physiology, 32(1), 1–7. https://doi.org/10.1159/000493641 Rajkumar, J., Chandan, N., Lio, P., & Shi, V. (2023). The Skin Barrier and Moisturization: Function, Disruption, and Mechanisms of Repair. Skin pharmacology and physiology, 36(4), 174–185. https://doi.org/10.1159/000534136 Williams, M. R., Costa, S. K., Zaramela, L. S., Khalil, S., Todd, D. A., Winter, H. L., . . . Gallo, R. L. (2019). Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis. Science Translational Medicine, 11(490), eaat8329. doi:10.1126/scitranslmed.aat8329 Zheng, Y., Hunt, R. L., Villaruz, A. E., Fisher, E. L., Liu, R., Liu, Q., Cheung, G. Y. C., Li, M., & Otto, M. (2022). Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell host & microbe, 30(3), 301–313.e9. https://doi.org/10.1016/j.chom.2022.01.004

Alopecia (hair loss) can be caused by factors such as reduced physiological function, scalp tension-induced blood flow disorders, genetic predisposition and poor scalp nutrition. While microbiome-focused research into alopecia is limited, biomolecules of fermented fruits and fermenting microbes show promise as a potential solution. What We Know: Studies investigating the scalp microbiome determined that Cutibacterium spp. and Staphylococcus spp. make up approximately 90% of a healthy scalp microbiome, with the remaining 10% consisting of Corynebacterium spp., Streptococcus spp., Acinetobacter spp. and Prevotella spp (Jo et al., 2022). The scalp microbiome may impact scalp health and alopecia. Research indicates no variance in species diversity or abundance between alopecia-affected and healthy scalps. However, a study found a >10% difference in Proteobacteria and Actinobacteria distributions. Healthy scalps showed higher Proteobacteria abundance, while alopecia-affected scalps had higher Actinobacteria levels (Jo et al., 2022). Fermented aloe vera and kimchi were successfully used to treat burn wounds and improve the skin microbiota pattern, maintaining probiotic (saprophytic) bacteria, including Lactobacillus, and reducing pathogenic bacteria (such as Prevotella and Cutibacterium acnes) (Yoon et al., 2022; Park et al., 2020). Industry Impact and Potential: Hair care products containing fermented papaya and mangosteen improved hair shaft conditions and reduced hair loss compared to control groups, showing potential for alopecia (Mayer et al., 2023). These experimental products improved the scalp microbiota, correcting the alopecia-associated altered microbiota pattern by decreasing pathogen content whilst maintaining probiotic (saprophyte) levels (Mayer et al., 2023). Fermented papaya's probiotic activity may involve selectively inhibiting catalase in microbial pathogens, which they rely on for enzymatic antioxidant defence against the host's immune response (Mayer et al., 2023). Further studies are needed to explore the preclinical and clinical effects of using food-grade fermented products in cosmetics, aiming to better understand their mechanisms and potential benefits for hair health. Integrating phytochemical and biological experiments could help identify specific plant- and microbe-derived substances with hair loss prevention and hair quality enhancement properties (Mayer et al., 2023). Our Solution: With a vast database of over 20,000 microbiome samples and 4,000 ingredients, coupled with a global network of over 10,000 testing participants, Sequential offers comprehensive services to evaluate product impacts and formulations. Our customisable microbiome studies provide real-life context testing, while formulation support ensures products maintain biome integrity. Therefore, we are your ideal candidate to utilise our solutions for your product development and efficacy. References: Jo, H., Kim, S.Y., Kang, B.H., Baek, C., Kwon, J.E., Jeang, J.W., Heo, Y.M., Kim, H.-B., Heo, C.Y., Kang, S.M., Shin, B.H., Nam, D.Y., Lee, Y.-G., Kang, S.C. & Lee, D.-G. (2022) Staphylococcus epidermidis Cicaria, a Novel Strain Derived from the Human Microbiome, and Its Efficacy as a Treatment for Hair Loss. Molecules. 27 (16). doi:10.3390/molecules27165136. Mayer, W., Weibel, M., De Luca, C., Ibragimova, G., Trakhtman, I., Kharaeva, Z., Chandler, D.L. & Korkina, L. (2023) Biomolecules of Fermented Tropical Fruits and Fermenting Microbes as Regulators of Human Hair Loss, Hair Quality, and Scalp Microbiota. Biomolecules. 13 (4), 699. doi:10.3390/biom13040699. Park, D.-W., Lee, H.S., Shim, M.-S., Yum, K.J. & Seo, J.T. (2020) Do Kimchi and Cheonggukjang Probiotics as a Functional Food Improve Androgenetic Alopecia? A Clinical Pilot Study. The World Journal of Men’s Health. 38 (1), 95–102. doi:10.5534/wjmh.180119. Yoon, Y.C., Ahn, B.H., Min, J.W., Lee, K.R., Park, S.H. & Kang, H.C. (2022) Stimulatory Effects of Extracellular Vesicles Derived from Leuconostoc holzapfelii That Exists in Human Scalp on Hair Growth in Human Follicle Dermal Papilla Cells. Current Issues in Molecular Biology. 44 (2), 845–866. doi:10.3390/cimb44020058.

Sudden skin reactions to skincare products can result from various factors, such as the introduction of new allergens, shifts in skin sensitivity, and the cumulative impact of product usage. Understanding these responses involves examining the allergens in cosmetics, the mechanisms behind skin reactions, and the influence of individual skin conditions. Types of allergens in skincare products Fragrance and preservatives: Common allergens like fragrances such as hydroxyisohexyl-3-cyclohexene carboxaldehyde, and preservatives like formaldehyde, parabens are frequently associated with allergic contact dermatitis (White & Groot, 2011). These ingredients can sensitize the skin over time, making it more reactive with continued exposure. Hair dyes: Ingredients such as p-phenylenediamine, often found in hair dyes, can cause allergic reactions, including redness, swelling, and itching around the scalp and face (White & Groot, 2011). Plant and Animal Derivatives: Natural components derived from plants and animals can provoke skin reactions, especially in sensitive individuals. Examples include lanolin, often derived from sheep's wool, and botanical extracts (Verhulst & Goossens, 2016). Alcohols and Acids:   Alcohols and exfoliating agents like glycolic acid or salicylic acid are popular in skincare for their renewing properties. However, they can irritate sensitive or damaged skin, causing redness and burning sensations (Verhulst & Goossens, 2016). Mechanisms of skin reactions Immediate Contact Reactions:  Some people experience Contact Urticaria Syndrome (CUS), where symptoms such as wheals or redness appear within minutes of exposure to a certain substance (Giménez-Arnau et al., 2010). Cumulative Sensitization: Repeated exposure to certain allergens can lead to cumulative sensitization, where skin that initially tolerated a product begins to react adversely over time (Wolf et al ., 2001). Skin Barrier Dysfunction:  A compromised skin barrier, due to over-exfoliation, dehydration, or pre-existing conditions becomes more permeable to irritants and allergens, increasing the risk of reactions (Engebretsen & Thyssen, 2016). Individual Factors Influencing Reactions Skin type:  People with sensitive skin, eczema, or rosacea are more prone to adverse reactions to skincare products. These conditions make the skin barrier more fragile and reactive. Age and Hormonal Changes: Aging skin or hormonal fluctuations, such as those occurring during pregnancy or menopause, can alter the skin's physiology, making it more sensitive and less resilient. Environmental Stressors: External factors like climate changes, UV exposure, pollution, or high stress can exacerbate skin sensitivity, increasing the likelihood of adverse reactions. Conclusion Most cosmetic products are considered safe for use, and proper diagnostic tools, such as patch testing, play a crucial role in identifying specific allergens and distinguishing between allergic and irritant reactions, enabling effective management and prevention strategies (Lazzarini, Duarte & Ferreira, 2013). Understanding the intricate mechanisms behind these reactions is essential for maintaining skin health. References Engebretsen KA, Thyssen JP. Skin Barrier Function and Allergens. Curr Probl Dermatol.  2016;49:90-102. doi: 10.1159/000441548. Epub 2016 Feb 4. PMID: 26844901. Lazzarini R, Duarte I, Ferreira AL. Patch tests. An Bras Dermatol. 2013  Nov-Dec;88(6):879-88. doi: 10.1590/abd1806-4841.20132323. PMID: 24474094; PMCID: PMC3900336. Wolf, R., Wolf, D., Tuzun, B., & Tuzun, Y. (2001). Cosmetics and contact dermatitis.  Dermatologic Therapy, 14(3), 181–187. doi:10.1046/j.1529-8019.2001.01025.x  White, Jonathan & De Groot, Anton - Ton & White, Ian. (2011). Cosmetics and Skin Care  Products. 10.1007/978-3-642-03827-3_32.  Verhulst L, Goossens A. Cosmetic components causing contact urticaria: a review and  update. Contact Dermatitis. 2016 Dec;75(6):333-344. doi: 10.1111/cod.12679. Epub 2016 Sep 4. PMID: 27593503.

Testing skincare products requires a structured approach to assess the products effectiveness and safety. This involves various methods, including in vitro testing, and clinical trials. As a consumer, testing skincare requires the products compatibility with personal needs. These testing include methods such as in-store testing, and patch testing. Testing methodologies  In vitro testing In vitro testing plays a critical role in assessing the safety and efficacy of skincare products. Under the European legislation, the evaluation of individual cosmetic ingredients is essential, with a strict prohibition on animal testing for cosmetic ingredients and products since 2004 and 2009, respectively. Additionally, the sale of products containing ingredients tested on animals has been banned since 2009 (Almeida, Sarmento & Rodrigues, 2017).  To meet these regulatory requirements, the European Centre for the Validation of Alternative Methods (ECVAM) has developed and validated various in vitro models such as skin irritation potential on cultured human or mammalian cell lines, skin cytotoxicity, skin and eye corrosion and irritation, phototoxicity…etc, to predict the safety and toxicity of cosmetic ingredients. These cell-based systems are valuable tools that provide reliable alternatives to animal testing, enabling researchers to evaluate factors such as absorption, permeability, and potential toxicity  (Almeida, Sarmento & Rodrigues, 2017).  Clinical trials Clinical trials are crucial for evaluating the performance of skincare products on human subjects. They consist of different phases and each phase typically involves a significant number of participants and incorporate both subjective feedback and objective assessments.  For example, a 4-week clinical study with 176 participants tested five targeted skincare formulations addressing irritated skin, dry skin, aging skin, oily skin, and dark circles. Results from the clinical study showed significant improvements in all conditions, with the products proving effective and safe, and no adverse effects (Duschek et al ., 2022). Consumer evaluation methods In store testing This allows consumers to directly observe the immediate effects of a skincare product on their skin. By evaluating factors such as texture, absorption, and any visible improvements, such as reduced redness or smoother skin, consumers can gain insight into the product's performance. This first hand observation is important, as it provides a sense of how the product may work for their individual skin needs. Patch testing Before using a new skincare product, it's advised to do a patch test. This involves applying a small amount of the product to a small area of your skin, like behind your ear or on your wrist, and leaving it for a certain period of time (usually 24-48 hours). This allows you to check for any signs of irritation, redness, or allergic reaction before applying the product to larger areas of your skin. It's a simple way to test if the product is safe to use. Conclusion In conclusion, testing skincare products is a crucial step in ensuring the products safety, effectiveness, and suitability for individual skin needs. There are a variety of testing methods that help provide a comprehensive understanding of how products perform. While in vitro models offer an ethical alternative to animal testing and clinical trials provide valuable insights into product performance, consumer methods are crucial to allow individuals to assess the product's compatibility with their own skin.  References Almeida, A., Sarmento, B., & Rodrigues, F. (2017). Insights on in vitro models for safety and  toxicity assessment of cosmetic ingredients. International Journal of Pharmaceutics, 519(1-2), 178–185. doi:10.1016/j.ijpharm.2017.01.024  Duschek N, Cajkovsky M, Prinz V, Müller D, Hundsamer A, Baierl A, Möllhoff N, Sulovsky M,  Frank K. An open-label, 4-week, prospective clinical study evaluating the efficacy and safety of a novel targeted skin care line addressing five common skin conditions. J Cosmet Dermatol. 2022 Nov;21(11):5760-5768. doi: 10.1111/jocd.15223. Epub 2022 Jul 28. PMID: 35810352.

The reason that skin appears healthier without the use of skincare products stems from various factors, such as, over-cleansing, and certain products could contain ingredients that may irritate skin. Therefore, simplifying skincare routines could enhance the skin’s natural balance and appearance.  Over-cleansing and skin health Over-cleansing is a key factor in improved skin appearance when skincare is avoided, as excessive washing strips the skin of its natural oils, causing dryness and irritation. A study done by Sverdrup showed that dry skin which is common in fibromyalgia patients' skin worsened by cosmetic use and aggressive cleansing routines (Sverdrup, 2004). The skin's natural oils are essential for hydration and maintaining the barrier function and their excess removal can trigger increased oil production, creating a cycle of dryness and oiliness that impacts the skin's overall appearance (Güell & Schneider, 2023). Irritation from ingredients Many skincare products contain chemicals and fragrances that can irritate the skin, causing redness, breakouts, or other adverse reactions. The growing popularity of "free from" claims in cosmetics reflects concerns about allergens and irritants, with avoiding such products potentially reducing irritation and promoting clearer skin (Nobile, 2016).  Regular use of products with harsh ingredients can also increase skin sensitivity, making it more reactive to environmental factors, while minimizing product use may help restore the skin’s natural resilience. Moreover, the skin has an ability to maintain its health and appearance when allowed to function naturally. The epidermis, the skin's outermost layer, acts as a protective barrier against environmental stressors. Discontinuing the use of potentially irritating products enables the skin to restore its natural balance and operate more efficiently (Lim, 2021). A study involving different age groups and lifestyles found that ceasing the use of potentially irritating products allowed the skin to restore its natural hydration and protective barrier, resulting in noticeable improvements. Younger individuals and new mothers, who often have less time for self-care, reported significant boosts in skin appearance and self-esteem when following simple skincare routines, highlighting how excessive or misused products can sometimes overwhelm the skin (Zhang et al ., 2020). The skin's microbiome plays a vital role in maintaining skin health as well. Overuse of cleansers and other products can disrupt the delicate balance of beneficial bacteria on the skin, leading to conditions such as acne or eczema (Hwang et al ., 2021). Hence it is important to incorporate products that support the skin microbiome rather than hindering it. Conclusion While a simplified approach to skincare may improve skin appearance for some individuals by reducing irritation and allowing the skin’s natural functions to flourish, it is important to balance this approach with targeted and purposeful skincare. Over-cleansing and the use of harsh or unsuitable products can disrupt the skin barrier, leading to cycles of dryness, oiliness, and sensitivity. However, well-formulated skincare routines that incorporate gentle cleansers, moisturizers, and sun protection can enhance the skin's resilience and prevent long-term damage from environmental stressors. Ultimately, the key to healthy skin lies in understanding individual skin needs and using products that support the balance of the skin. References Güell M, Schneider MR. In preprints: progress in sebaceous gland homeostasis,  regeneration and immunomodulatory functions. Development. 2023 Aug 1;150(15):dev202177. doi: 10.1242/dev.202177. Epub 2023 Jul 31. PMID: 37522362. Hwang BK, Lee S, Myoung J, Hwang SJ, Lim JM, Jeong ET, Park SG, Youn SH. Effect of  the skincare product on facial skin microbial structure and biophysical parameters: A pilot study. Microbiologyopen. 2021 Oct;10(5):e1236. doi: 10.1002/mbo3.1236. PMID: 34713611; PMCID: PMC8494714. Lim KM. Skin Epidermis and Barrier Function. Int J Mol Sci. 2021 Mar 16;22(6):3035. doi:  10.3390/ijms22063035. PMID: 33809733; PMCID: PMC8002265. Nobile, Vincenzo. “Misleading Marketing of Cosmetics. Do the Free from Parabens and Free  from Allergenic Substances Claims Really Make Sense.” (2016). Sverdrup B. Use less cosmetics--suffer less from fibromyalgia? J Womens Health (Larchmt).  2004 Mar;13(2):187-94. doi: 10.1089/154099904322966173. PMID: 15072733. Zhang, L., Adique, A., Sarkar, P., Shenai, V., Sampath, M., Lai, R., … & Farage, M. A.  (2020). The impact of routine skin care on the quality of life. Cosmetics, 7(3), 59. https://doi.org/10.3390/cosmetics7030059