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- Hormonal Harmony: How Do the Menstrual Cycle and Hormonal Contraception Influence the Vaginal Microbiome?
While age, environment and genetics are known to affect the vaginal microbiome, the impact of hormonal fluctuations during the menstrual cycle and the use of hormonal contraceptives is less clear. Emerging research is now starting to address these influences and explore solutions for imbalances. What We Know: The vaginal microbiome is generally dominated by Lactobacillus spp. and this is thought to be regulated by oestradiol and progesterone levels. This dominance is more prevalent during reproductive years when these hormones are high. In contrast, prepubescent girls and postmenopausal women, who have lower hormone levels, typically have a more diverse vaginal microbiome with reduced Lactobacillus abundance (Krog et al., 2022) . Research has yet to explore the long term impact of fluctuating sex hormones during the menstrual cycle and the potential effects of hormonal contraception on microbiome composition (Krog et al., 2022) . Industry Impact and Potential: Hormonal contraceptives do not significantly alter the composition of the vaginal microbiome. Studies have shown that regardless of the contraceptive method used, the abundances of key species such as Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis and Prevotella spp. remain consistent (Krog et al., 2022) . However, the vaginal microbiome undergoes significant changes throughout the menstrual cycle, particularly in women not using hormonal contraceptives. During the follicular and luteal phases, there is an increase in L. crispatus , alongside a decrease in eight bacterial vaginosis-associated species. This pattern reflects a shift in microbial balance that aligns with hormonal fluctuations throughout the cycle. Notably, Lactobacillus species showed positive correlations with serum oestradiol levels and higher levels of L. iners were associated with increased oestradiol (Krog et al., 2022) . The reasons for increased microbiome diversity during menstruation, whether due to hormonal shifts, iron availability from menstrual blood or the impact of menstrual hygiene products, are still unconfirmed. However, findings suggest that menstrual products and sexual practices have only a minor effect on these microbial changes (Krog et al., 2022) . This study was the first to measure serum oestradiol levels and find a link between high oestradiol and the presence of L. crispatus , indicating that hormones help maintain this beneficial microbe (Krog et al., 2022) . Earlier this year, @Seed Health launched VS-01™, a pioneering vaginal suppository synbiotic featuring three proprietary strains of L. crispatus . Clinically validated to optimise the vaginal microbiome, VS-01™ has been shown to effectively regulate pH levels within one menstrual cycle (Microbiome Post, 2024) . Our Solution: In addition to vaginal 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 assessment and development of products that maintain microbiome integrity. Our team of experts is well-equipped to support your company in formulating innovative products suitable for maintaining and improving the vaginal microbiome to support women’s health. References: Krog, M.C., Hugerth, L.W., Fransson, E., Bashir, Z., Nyboe Andersen, A., Edfeldt, G., Engstrand, L., Schuppe-Koistinen, I. & Nielsen, H.S. (2022) The healthy female microbiome across body sites: effect of hormonal contraceptives and the menstrual cycle. Human Reproduction (Oxford, England). 37 (7), 1525–1543. doi:10.1093/humrep/deac094. Microbiome Post (2024) Seed Health introduces revolutionary vaginal microbiome product: VS-01.
- AOB for AD: Ammonium-oxidising Bacteria as an Innovative Approach to Managing Atopic Dermatitis
Atopic Dermatitis (AD) is a chronic inflammatory skin condition characterised by skin barrier dysfunction and immune dysregulation. Treatment is often difficult and multifaceted, including topical corticosteroids and moisturisers, but recent research has explored ammonium-oxidising bacteria (AOB) as a promising novel approach. What We Know: Skin microbiome dysbiosis is a common feature of AD, characterised by low bacterial diversity, high non-Malassezia fungal diversity, an increased abundance of Staphylococcus aureus and Staphylococcus epidermidis , and reduced levels of other bacterial genera, with S. aureus colonisation notably worsening disease severity (Bjerre et al., 2017) . Treating AD involves regular use of emollients, soap-free cleansers, corticosteroids for flare-ups, and broad-spectrum antibiotics targeting S. aureus. Emerging microbiome-based biotherapies, such as probiotics, microbial repopulation, phage therapies, small molecules, monoclonal antibodies, and quorum sensing inhibitors, show promise in addressing S. aureus colonization (Koh, Ong & Common, 2022). AD is driven by an uncontrolled type 2 inflammatory response involving cytokines IL-5, IL-13, and IL-4, which lead to IgE production, hypersensitivity reactions, itching, and tissue damage. Consequently, therapeutic strategies targeting type 2 cells and their cytokine mediators, such as IL-5, IL-13, and IL-4, have shown promise in managing these conditions (Maura, Elmekki & Goddard, 2021) . Research identifies Nitrosomonas eutropha D23, an ammonia-oxidizing bacteria, as a promising candidate for modulating the T2 pathway. It suppresses Th2 cell polarization and cytokine production, likely via IL-10 and dendritic cell inhibition, suggesting its potential for treating atopic skin diseases (Maura, Elmekki & Goddard, 2021). Industry Impact and Potential: AOBiome Therapeutics, Inc., has developed B244: a patented live topical biotherapeutic containing a purified strain of Nitrosomonas eutropha, originally isolated from soil samples, that may help manage AD by reducing pathogenic bacteria like S. aureus (Silverberg et al., 2023) . B244 generates nitric oxide, which helps regulate inflammation and blood vessel dilation by reducing cytokines (IL-4, IL-5, IL-13, IL-31) associated with AD symptoms. Its metabolic, antimicrobial properties, and lack of virulence make it a promising, well-tolerated topical treatment for AD (Silverberg et al., 2023). Global Phase 3 trials are imminent, with AOBiome partnering with Maruho Co., Ltd. for the treatment's commercialization. Our Solution: Sequential is an industry-leading microbiome product developing and testing company based in London, New York and Singapore. Our expertise and customisable services empower businesses to innovate confidently in formulating and investigating products that preserve microbiome integrity, ensuring their efficacy and compatibility for a healthier microbiome. References: Bjerre, R.D., Bandier, J., Skov, L., Engstrand, L. & Johansen, J.D. (2017) The role of the skin microbiome in atopic dermatitis: a systematic review. British Journal of Dermatology . 177 (5), 1272–1278. doi:10.1111/bjd.15390. Koh, L.F., Ong, R.Y. & Common, J.E. (2022) Skin microbiome of atopic dermatitis. Allergology International . 71 (1), 31–39. doi:10.1016/j.alit.2021.11.001. Maura, D., Elmekki, N. & Goddard, C.A. (2021) The ammonia oxidizing bacterium Nitrosomonas eutropha blocks T helper 2 cell polarization via the anti-inflammatory cytokine IL-10. Scientific Reports . 11 (1), 14162. doi:10.1038/s41598-021-93299-1. Silverberg, J.I., Lio, P.A., Simpson, E.L., Li, C., Brownell, D.R., Gryllos, I., Ng-Cashin, J., Krueger, T., Swaidan, V.R., Bliss, R.L. & Kim, H.D. (2023) Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. eClinicalMedicine . 60. doi:10.1016/j.eclinm.2023.102002.
- What can be done to support the infant microbiome?
Infant skin is sensitive, becoming easily irritated by harsh chemicals and textures. As parents become more aware of the importance of the cutaneous microbiome for their child’s health, the greater demand for a range of safe & effective brands that work to strengthen & support infant skin. Many microbiome-based solutions have emerged for the effective treatment of neonatal conditions and maintenance of a healthy skin microbiome. What we know: The infant skin microbiota is as diverse and complex as adults. These communities work to protect the skin from infection and maintain healthy function, yet can still be influenced by external factors like mode of delivery/feeding, home environment and skin care products (Murphy et al 2023). The infant is first heavily colonised by Streptococcus & Acinetobacter, while the population of C. acnes & Malassezia remains quite low until sebaceous gland maturation takes place for them to feed from. These species may contribute to skin acidification following birth through lactic acid production, with this acid mantle forming an additional protective layer over the skin (Murphy et al 2023) Studies have shown skin microbiome dysbiosis in infants can influence skin health, shifts towards Pseudomonas & gut-derived Enterococcus observed in infants with diaper dermatitis (DD) - likely the result of the moist & anaerobic diaper microenvironment, alongside its proximity to the intestinal tract (Zheng et al 2019) Other factors of DD include faecal exposure, sweat, friction and skin pH that can promote selective growth of intestinal microbes and pathogens that thrive in these environments. Besides bacteria, this also includes fungi like Candida & Cladosporium that trigger rashes & inflammation (Teufel et al 2021) Erythema toxicum neonatorum is a neonatal skin condition that may be influenced by the establishment of the infant skin microbiome. Usually involving penetration of bacteria into the hair canal, triggering the immune system into producing an inflammatory response. Some studies have reported various species of Staphylococcus bacteria being present in these lesions (Marchini et al 2005) Industry impact & potential: A Tapir's Tale's child-friendly skin care brand makes use of natural plant-derived ingredients to offer gentle products suitable for infants with sensitive & atopic skin conditions. Kiss Kiss Goodnight’s plant-based yellow star prebiotic jelly-to-milk cleanser contains prebiotics supporting the infant microbiome in the diaper area to nourish & protect skin from irritation & diaper rash. Our solution: Here at Sequential we care about providing the best invivo testing for your brand, especially when considering something as delicate as an infant’s skin. Our detailed clinical microbiome reports allow us to characterise your formulation with great precision to support with delivering on its promise. References: Marchini G, Nelson A, Edner J, Lonne-Rahm S, Stavréus-Evers A, Hultenby K. Erythema toxicum neonatorum is an innate immune response to commensal microbes penetrated into the skin of the newborn infant. Pediatr Res. 2005 Sep;58(3):613-6. doi: 10.1203/01.pdr.0000176836.27156.32. PMID: 16148082. Murphy B, Hoptroff M, Arnold D, Cawley A, Smith E, Adams SE, Mitchell A, Horsburgh MJ, Hunt J, Dasgupta B, Ghatlia N, Samaras S, MacGuire-Flanagan A, Sharma K. Compositional Variations between Adult and Infant Skin Microbiome: An Update. Microorganisms. 2023 Jun 2;11(6):1484. doi: 10.3390/microorganisms11061484. PMID: 37374986; PMCID: PMC10304506. Teufel A, Howard B, Hu P, Carr AN. Characterization of the microbiome in the infant diapered area: Insights from healthy and damaged skin. Exp Dermatol. 2021 Oct;30(10):1409-1417. doi: 10.1111/exd.14198. Epub 2020 Oct 13. PMID: 32974911; PMCID: PMC8518357. Zheng Y, Wang Q, Ma L, Chen Y, Gao Y, Zhang G, Cui S, Liang H, Song L, He C. Shifts in the skin microbiome associated with diaper dermatitis and emollient treatment amongst infants and toddlers in China. Exp Dermatol. 2019 Nov;28(11):1289-1297. doi: 10.1111/exd.14028. Epub 2019 Sep 16. PMID: 31472099.
- Green Guardians: Exploring Plant-Derived Antifungals in Skincare Innovation
Plants possess a multitude of naturally evolved mechanisms to help prevent and protect against fungal infection, and humans have been using them for thousands of years to help treat skin conditions. Scientific innovation has now made it possible to discover specific plant-derived ingredients responsible for driving these antifungal effects for use in further cosmetic formulation. What we know: Plant extracts (PEs) from species like Phytolacca tetramera, Clematis flammula & Fraxinus angustifolia have the potential to improve skin microbiome modulation in response to dysbiotic fungal infections by strains of Candida spp by targeting the destruction of yeast cells and inhibiting the formation of biofilms exacerbate fungal growth and intensity of infection (Butassi et al., 2019; Ourabah et al., 2019) One study investigating the efficacy of vegetable-derived PEs in treating yeast and dermatophyte infections found both onion & garlic showed significant antifungal activity against Malassezia furfur, Candida albicans, and dermatophytes species (Shams-Ghahfarokhi et al., 2006) Onion extracts contain thiosulfinates & phenolics that have proven antifungal properties owing to their inhibitory effect on fungal growth. Garlic contains bioactives like allicin and sulphides that promote both antibacterial and antifungal effects (Zhao et al., 2021; Bar et al., 2022) Plant essential oils (EOs) also possess antifungal capabilities, acting similarly to PEs by disrupting fungal cells. One of the most effective types of EO are those extracted from thyme, showing highly potent fungicidal effects against Aspergillus, a group of fungi responsible for cutaneous aspergillosis as well as certain Candida species (Abd Rashed et al., 2021) Melaleuca alternifolia EO is also a proven treatment against fungal infection, containing compounds like α-pinene, γ-terpinene & limonene that act to restrict Malassezia growth on the skin and prevent diseases like pityriasis versicolor & seborrhoeic dermatitis (de Groot et al., 2016; Hammer et al., 2000) Industry impact & potential: Plant extracts and essential oils are now considered major constituents of various cosmetic formulations owing to their antimicrobial properties. Malezia 5% Urea Moisturizer contains plant-derived ingredients like Caprylic/Capric Triglyceride & Allantoin that act to prevent Malassezia growth while moisturising fungal acne prone skin. Almond Clear’s mandelic acid serum contains almond-derived ingredients that combat bacteria and fungi to reduce acne and folliculitis while exfoliating the skin. Our solution: As an industry leader in skin microbiome testing, Sequential offers end-to-end support for products supplying the microbiome with beneficial effects, including the reduction of fungus-associated conditions like Malassezia folliculitis or seborrheic dermatitis. References: Abd Rashed A, Rathi DG, Ahmad Nasir NAH, Abd Rahman AZ. Antifungal Properties of Essential Oils and Their Compounds for Application in Skin Fungal Infections: Conventional and Nonconventional Approaches. Molecules. 2021 Feb 19;26(4):1093. doi: 10.3390/molecules26041093. PMID: 33669627; PMCID: PMC7922942. de Groot AC, Schmidt E. Tea tree oil: contact allergy and chemical composition. Contact Dermatitis. 2016 Sep;75(3):129-43. doi: 10.1111/cod.12591. Epub 2016 May 13. PMID: 27173437. Bar, Monika & Binduga, Urszula & Szychowski, Konrad. (2022). Methods of Isolation of Active Substances from Garlic (Allium sativum L.) and Its Impact on the Composition and Biological Properties of Garlic Extracts. Antioxidants. 11. 1345. 10.3390/antiox11071345. Butassi E, Svetaz LA, Zhou S, Wolfender JL, Cortés JCG, Ribas JC, Díaz C, Palacio JP, Vicente F, Zacchino SA. The antifungal activity and mechanisms of action of quantified extracts from berries, leaves and roots of Phytolacca tetramera. Phytomedicine. 2019 Jul;60:152884. doi: 10.1016/j.phymed.2019.152884. Epub 2019 Mar 16. PMID: 30922815. Hammer KA, Carson CF, Riley TV. Melaleuca alternifolia (tea tree) oil inhibits germ tube formation by Candida albicans. Med Mycol. 2000 Oct;38(5):355-62. PMID: 11092382. Ourabah, Asma & Atmani-Kilani, Dina & Nadjet, Benaida & Kolesova, Olga & Azib, Lila & Yous, Farah & Benloukil, Malika & Botta, Bruno & Atmani, Djebbar & Simonetti, Giovanna. (2019). Anti-Candida albicans biofilm activity of extracts from two selected indigenous Algerian plants: Clematis flammula and Fraxinus angustifolia. Journal of Herbal Medicine. 20. 100319. 10.1016/j.hermed.2019.100319. Shams-Ghahfarokhi M, Shokoohamiri MR, Amirrajab N, Moghadasi B, Ghajari A, Zeini F, Sadeghi G, Razzaghi-Abyaneh M. In vitro antifungal activities of Allium cepa, Allium sativum and ketoconazole against some pathogenic yeasts and dermatophytes. Fitoterapia. 2006 Jun;77(4):321-3. doi: 10.1016/j.fitote.2006.03.014. Epub 2006 May 11. PMID: 16690223. Zhao XX, Lin FJ, Li H, Li HB, Wu DT, Geng F, Ma W, Wang Y, Miao BH, Gan RY. Recent Advances in Bioactive Compounds, Health Functions, and Safety Concerns of Onion ( Allium cepa L.). Front Nutr. 2021 Jul 22;8:669805. doi: 10.3389/fnut.2021.669805. PMID: 34368207; PMCID: PMC8339303.
- What is psycare? The mental health movement taking the cosmetic world by storm
Psycare is a cosmeceutical trend prioritising wellbeing and a holistic approach to skincare that promotes emotional and psychological healing in the face of the stresses experienced by consumers today. What we know: A report released in 2023 reported 46% of global consumers prioritise mental and physical wellness when making purchasing decisions, choosing to embrace a more health-focused approach compared to previous years (NIQ, 2023) Plant fragrance therapy has been found to positively regulate negative psychological and behavioural dispositions by stabilising brain waves to improve self-regulation and immunity while lowering physical and mental stress, indicating potential use in psycare products centering around relaxant essential oils and fragrances to promote positive thinking (Kim et al., 2021) Psychedelic-based products like those containing psilocybin may be able to slow down skin ageing at a genetic level as well as target other dermatological conditions associated with inflammation such as atopic dermatitis by blocking action of skin receptors that drive this response (Gerasymchuk et al. 2023) A survey by the British Skin Foundation reported 53% of respondents with a skin condition feel judged by others because of it, with 35% claiming their condition also impacts their mental health. Inclusion of ingredients like azelaic acid & probiotics may also help reduce the appearance of common skincare concerns like acne and rosacea by restoring balance to the dysbiotic microbiome responsible for worsening these conditions and in doing so improve mental wellness and consumer self confidence (BSF 2021; Lee et al., 2019; Zhu et al., 2023) Industry impact & potential: Lagalene Milano ‘beauty is a choice’ has curated a brand centering round the holistic beauty concept, integrating elements of essential oil fragrances like bergamot and cedar to promote psychophysical well-being and removing anxiety and stress, while also targeting skincare concerns such as acne and wrinkles. Selfmade® is a psychodermatology-inspired beauty brand espousing the philosophy of self care and intersectionality to promote self-confidence in its consumers while offering natural products to treat oily, blemished, and dry skin. Our solution: Sequential is an experienced player in End-to-End invivo testing of cosmetic products, partnering with several industry leads seeking to maximise product performance and formulation, and providing personalised guidance and advice for brands seeking to validate their claims for skin microbiome health. We offer in-depth clinical candidate reports, meaning we can tailor the aims of your brand to match our testing expertise, providing a means for you to test both the physical and psychological effects of your product. References: BSF (2023). Over half of those with a skin condition feel judged by others. Retrieved from https://www.britishskinfoundation.org.uk/news/over-half-of-those-with-a-skin-condition-feel-judged-by-others Gerasymchuk M, Robinson GI, Vardinska N, Ayedun SA, Alozie SC, Robinson JW, Kovalchuk O, Kovalchuk I. Sex-Dependent Skin Aging and Rejuvenation Strategies. Dermato . 2023; 3(3):196-223. https://doi.org/10.3390/dermato3030016 Kim, J., Sin, C., Park, J., Lee, H., Kim, J., Kim, D., & Kim, S. (2021). Physiological and psychological effects of forest healing focused on plant fragrance therapy for maladjusted soldiers. Journal of People Plants Environment , 24(4), 429-439. https://doi.org/10.11628/ksppe.2021.24.4.429 Lee YB, Byun EJ, Kim HS. Potential Role of the Microbiome in Acne: A Comprehensive Review. Journal of Clinical Medicine . 2019; 8(7):987. https://doi.org/10.3390/jcm8070987 NIQ. (2023). 2023 State of the Beauty Industry. Retrieved from https://nielseniq.com/global/en/insights/report/2023/2023-state-of-the-beauty-industry/ Zhu Y, Yu X, Cheng G. Human skin bacterial microbiota homeostasis: A delicate balance between health and disease. mLife. 2023 Jun 4;2(2):107-120. doi: 10.1002/mlf2.12064. PMID: 38817619; PMCID: PMC10989898.
- How can brands work to reduce their plastic footprint?
More consumers now consider the environmental impact of their product choices. Companies can increase the reach of their customer base by switching to more sustainable forms of formulation & manufacturing that reduce the amount of microplastic waste generated. What we know: 1.3 million metric tons of microplastics (MPLs) enter the world’s oceans annually, predicted to increase to three million metric tons annually by 2040. Personal care products are responsible for only 2% of this, but are the only one classed as an intentional source of MPL loss into the planet’s waterways through inclusion of ingredients like microbeads (Statista 2023; Boucher & Friot 2017). Exposure to MPLs are linked to shifts in skin microbiome composition associated with loss of diversity & dysbiosis in marine animals. Entry of MPLs into human skin may cause inflammation, cell death & oxidative stress (Schirinzi et al., 2017). Formulations containing ingredients like polyethylene microbeads (now banned in several countries e.g. UK & US) and other synthetic polymers are the biggest sources of cosmetic MPLs (Leslie 2014). Degradation of plastic packaging is also a major source of secondary microplastics entering the environment from landfills and waste management facilities (Cubas et al., 2022). Some steps to reduce plastic footprints includes using biopolymers such as cellulose & polylactic acid as biodegradable alternatives to plastic packaging or substituting plastic ingredients with natural alternatives like plant lectins as an alternative to petroleum-derived preservatives, bacterial cellulose instead of polypropylene emulsifiers/thickeners, and microalgae in place of plastic UV filters (Cubas et al., 2022). Industry impact & potential: 81% of consumers believe cosmetic brands should actively reduce plastic package use, and with this change many companies have embraced low plastic practices to reduce waste. Food for Skin | B Corp has dedicated years of research into developing organic, all natural skincare formulations free of parabens and microplastics. Aveda has also taken steps to reduce waste generated from plastic packaging and ingredient formulations by using post-consumer recycled materials and bioplastics in their packaging. Our solution: As a testing company, Sequential has made its efforts to support the industry’s shift to an environmentally friendly business model, working closely with eco-conscious brands and reducing the amount of lab plastic waste. Sequential has also co-launched the industry’s first at-home consumer microbiome test with multiple international partners in the hopes of encouraging consumers to test their skin before purchasing skincare products to reduce the risk of purchasing products mismatched from their skin’s need. This allows for lower trial and error of purchasing products, resulting in less waste of skincare products. References: Boucher, Julien & Friot, Damien. (2017). Primary Microplastics in the Oceans: A Global Evaluation of Sources. 10.2305/IUCN.CH.2017.01.en. Cubas ALV, Bianchet RT, Reis IMASd, Gouveia IC. Plastics and Microplastic in the Cosmetic Industry: Aggregating Sustainable Actions Aimed at Alignment and Interaction with UN Sustainable Development Goals. Polymers . 2022; 14(21):4576. https://doi.org/10.3390/polym14214576 Leslie, H.A. (2014) Review of Microplastics in Cosmetics. Institute of Environmental Studies, VU University, Amsterdam. https://doi.org/10.1016/j.marpolbul.2016.05.046 Schirinzi GF, Pérez-Pomeda I, Sanchís J, Rossini C, Farré M, Barceló D. Cytotoxic effects of commonly used nanomaterials and microplastics on cerebral and epithelial human cells. Environ Res. 2017 Nov;159:579-587. doi: 10.1016/j.envres.2017.08.043. Epub 2017 Sep 11. PMID: 28898803. Statista. (2023). Managed and mismanaged microplastics worldwide in 2016 with a forecast to 2040 under business-as-usual scenario. Retrieved from https://www.statista.com/statistics/1270661/microplastic-pollution-projections-worldwide/
- What is the potential for AI in formulation development and personalisation?
Machine learning is a field of artificial intelligence (AI), that uses complex algorithms to predict outcomes based on training datasets. Using the term “AI” has become widespread in tech companies, including now in the consumer health and beauty sphere. Machine learning and AI are used interchangeably. Companies are now looking to employ new technologies to improve the efficacy of their personal care products and aid consumers to make more informed skin care decisions. What we know: The global AI market is expected to grow twenty fold over the next decade from 200bn USD to nearly two trillion USD by 2030. (Statistia, 2023) Following this trend, global cosmetic AI is currently valued at 3.22B USD and expected to grow by 19.6% between 2023 and 2031 to reach 15.75B USD 80% of American Gen Zs and 68.3% of European Gen Z are willing to trust AI for skincare recommendations (InsightAce Analytic 2023; Statistia, 2022ab) AI models are thought to be capable of predicting the sensitising potential of ingredients with an accuracy of 86%, sensitivity of 80%, and specificity of 90% using their physicochemical characteristics and previous data on animal and in vitro models, showing the potential of this technology to be used when developing formulations that remain true to life (Kalicińska et al., 2023) The surge in ‘generative AI’ has been implemented in formulation development and is thought to predict the effects of ingredients and their interactions on the skin, to a reasonable degree, especially for particular skin concerns (Vatiwutipong et al., 2023) AI could be used to make predictions of how skin might change over time and make suggestions accordingly, increasing consumer temporal awareness of their skin condition (Gilliland 2023) Industry impact & potential: Companies are turning to AI to provide detailed skin analysis for individuals to tailor their products specifically to their skin needs. Shiseido’s skincare advisor assesses the quality of an individual's skin in under two minutes drawing from their database of 30,000 images to provide specialised skincare recommendations. Haut.AI ’s Skin SaaS system evaluates an individual's face based on multiple skin metrics including acne condition, hydration, and wrinkling to recommend products based on current and future predictions of skin. Our solution: For AI to be used effectively in the microbiome world, we need to train machine learning algorithms on high quality datasets as a starting point. At Sequential, we have collected nearly 20,000 skin microbiome samples, and the effect of hundreds of formulations containing over 4,000 ingredients. Our next step is to leverage this database for novel biomarkers, and formulations for certain skin demographics. We also have an expert team in the microbiome and AI field, including our advisor Prof Eran Segal who is experienced with big microbiome datasets. References: InsightAce Analytic. (2023). 80% of American Gen Zs and 68.3% of European Gen Z are willing to trust AI for skincare recommendations. Retrieved from Kalicińska J, Wiśniowska B, Polak S, Spiewak R. Artificial Intelligence That Predicts Sensitizing Potential of Cosmetic Ingredients with Accuracy Comparable to Animal and In Vitro Tests-How Does the Infotechnomics Compare to Other "Omics" in the Cosmetics Safety Assessment? Int J Mol Sci. 2023 Apr 6;24(7):6801. doi: 10.3390/ijms24076801. PMID: 37047774; PMCID: PMC10094956. Statista. (2022a). 80% of American Gen Zs and 68.3% of European Gen Z are willing to trust AI for skincare recommendations. Retrieved from https://www.statista.com/statistics/1289772/gen-z-s-trust-in-ai-beauty-advisors-in-north-america/ Statista. (2023). The global AI market is expected to grow twenty fold over the next decade from 200bn USD to nearly two trillion USD by 2030. Retrieved from https://www.statista.com/outlook/tmo/artificial-intelligence/worldwide Vatiwutipong, Pat & Vachmanus, Sirawich & Noraset, Thanapon & Tuarob, Suppawong. (2023). Artificial Intelligence in Cosmetic Dermatology: A Systematic Literature Review. IEEE Access. PP. 1-1. 10.1109/ACCESS.2023.3295001.
- Could neurocosmetics be a solution to ageing skin?
Neurocosmetics is an emergent practice in the personal care space focusing on the connection between the nervous system and skin when designing formulations for products. Neurocosmetic ingredients have the capacity to influence the chemical and electrical modes of communication between the brain and skin to deliver more effective products and treatments when considering skin response to ageing. What we know: The close connection between the skin and nervous system means the two share similar physiological functions (i.e., thermoregulation, sebaceous secretion and melanogenesis) allowing them to communicate using neuropeptides and nerve impulses and respond to environmental stimuli e.g. chemicals, ultraviolet light rays, and temperature (Rizzi et al., 2021; Glatte et al., 2019). Neurocosmetics have the capacity to affect the brain’s response to topical skincare treatments to increase their effectiveness and can act through various means such as botulinum-like peptides (i.e., hexapeptides or plant extracts) acting on cutaneous nerves to relax facial muscles & avoid wrinkle formation (Rizzi et al., 2021). Achillea millefolium extract upregulates the expression of nervous skin receptors that decrease during the ageing process, with results showing increased epidermal thickness post-administration, and improved appearance of wrinkles and pores after 2 months of treatment (Pain et al., 2011) Chronic exposure to environmental stress can trigger enhanced cortisol production by the brain, leading to immunosuppression, inflammation, impaired barrier function, and increased DNA damage in the skin. Application of an active inhibitor against the 11β-HSD1 enzyme rebalances these levels by blocking the cortisol synthesis pathway (Chen & Lyga, 2014; Imfeld et al., 2018). Industry impact & potential: Many companies have started formulating their own active ingredients for sale and use by other brands looking to amplify the efficacy of their formulations. SEPPIC’s range of neurocosmetic ingredients emphasise the use of amino acid and plant extract compounds to protect the skin from stressors like antioxidants, inflammation, and anti-matrix metalloproteinase action. Givaudan’s active ingredient range includes Neurophroline® that works to break down cortisol production by releasing a calming neuropeptide that improves skin tone and anti-ageing effect. Our Solution: Sequential provides invivo Gold Standard testing of ingredient effect on the microbial, as well as physical properties of skin, with a specialist angle in the skin ageing market. Our service offers clients clinical studies to test the efficacy of your neurocosmetic ingredients or formulations on age parameters like corneometry and elasticity. We are also able to offer formulation support and INCI list examination to assess the effectiveness of your solutions for targeting ageing skin concerns. References: Chen Y, Lyga J. Brain-skin connection: stress, inflammation and skin aging. Inflamm Allergy Drug Targets. 2014;13(3):177-90. doi: 10.2174/1871528113666140522104422. PMID: 24853682; PMCID: PMC4082169. Glatte P, Buchmann SJ, Hijazi MM, Illigens BM, Siepmann T. Architecture of the Cutaneous Autonomic Nervous System. Front Neurol. 2019 Sep 10;10:970. doi: 10.3389/fneur.2019.00970. PMID: 31551921; PMCID: PMC6746903. Imfeld, D & Jackson, Eileen & Seroul, Pierre. (2018). Inhibition of cutaneous cortisol activation: A novel approach to protect skin from stress induced damage and aging.. Pain S, Altobelli C, Boher A, Cittadini L, Favre-Mercuret M, Gaillard C, Sohm B, Vogelgesang B, André-Frei V. Surface rejuvenating effect of Achillea millefolium extract. Int J Cosmet Sci. 2011 Dec;33(6):535-42. doi: 10.1111/j.1468-2494.2011.00667.x. Epub 2011 Jun 29. PMID: 21711463. Rizzi V, Gubitosa J, Fini P, Cosma P. Neurocosmetics in Skincare—The Fascinating World of Skin–Brain Connection: A Review to Explore Ingredients, Commercial Products for Skin Aging, and Cosmetic Regulation. Cosmetics . 2021; 8(3):66. https://doi.org/10.3390/cosmetics8030066
- Why does strain matter when testing ingredients?
Most bacterial species do not fall exclusively under the umbrella of mutualists or pathogens, with many possessing strains that lie across a continuum between the two extreme states. It is important to consider the effect of this when devising formulations to treat common skin disorders as the same ingredients used against pathogenic strains can wipe out beneficial populations helping to maintain skin health. What we know: The phylotype I strain of Cutibacterium acnes is more commonly associated with diseases such as acne vulgaris. It forms biofilms and secretes adhesion proteins that allow them to attach and invade neighbouring skin cells, causing disruption of the epithelial barrier and increasing risk of inflammation and infection (Spittaels et al., 2020). Other more beneficial strains of Cutibacterium acnes like type II instead secrete anti-inflammatory molecules, modulate the immune system, prevent colonisation by pathogens, and provide antioxidant activity to keep the skin healthy (Yu et al., 2016; Ahle et al., 2023). Staphylococcus epidermidis strains of Staphylococcus protect the skin by synthesising lantibiotics that target and kill more virulent strains like S. aureus, secreting enzymes that degrade pathogen biofilms, and releasing pheromones that restrict their ability to colonise and invade the skin (Cogen & Gallo 2008; Byrd et al., 2018). S. aureus releases virulence factors interfering with the cutaneous immune system (e.g., inflammation, white blood cell activation), secretes enzymes that damage skin tissue, and brings about dysbiotic changes to the skin’s normal microflora to trigger skin conditions like atopic dermatitis (Cogen & Gallo 2008; Geoghegan et al., 2018; Kobayashi et al., 2015). Cross-species strain interactions also control virulent populations. Corynebacterium accolens prevents Streptococcus pneumoniae from growing on the skin by generating fatty acids that make the external environment uninhabitable for it (Bomar et al., 2016). Industry Impact & potential: Prebiotics and phage therapies are now being considered as alternatives to traditional antibiotics for treating skin disorders owing to their greater level of strain specificity during treatment. Some brands are using ingredients containing C. acnes phages to target pathogenic strains while allowing healthy strains to persist. Other brands are also using prebiotic products to selectively promote the growth of good bacteria while restricting growth of harmful ones. Our solution: Sequential is able to offer invivo strain-specific testing of your product on the skin to help distinguish between the effects of your product on good and bad bacteria. Our experienced panel of experts can also help brands develop personalised formulations that act against bad bacteria while maintaining the good to maximise the effects of your ingredients and prevent any unwanted dysbiotic effects. References: Ahle CM, Feidenhansl C, Brüggemann H. Cutibacterium acnes. Trends Microbiol. 2023 Apr;31(4):419-420. doi: 10.1016/j.tim.2022.10.006. Epub 2022 Oct 31. PMID: 36328874. Bomar L, Brugger SD, Yost BH, Davies SS, Lemon KP. Corynebacterium accolens Releases Antipneumococcal Free Fatty Acids from Human Nostril and Skin Surface Triacylglycerols. mBio. 2016 Jan 5;7(1):e01725-15. doi: 10.1128/mBio.01725-15. PMID: 26733066; PMCID: PMC4725001. Byrd, A., Belkaid, Y. & Segre, J. The human skin microbiome. Nat Rev Microbiol 16, 143–155 (2018). https://doi.org/10.1038/nrmicro.2017.157 Cogen AL, Nizet V, Gallo RL. Skin microbiota: a source of disease or defence? Br J Dermatol. 2008 Mar;158(3):442-55. doi: 10.1111/j.1365-2133.2008.08437.x. PMID: 18275522; PMCID: PMC2746716. Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and Atopic Dermatitis: A Complex and Evolving Relationship. Trends Microbiol. 2018 Jun;26(6):484-497. doi: 10.1016/j.tim.2017.11.008. Epub 2017 Dec 9. PMID: 29233606. Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, Kong HH, Amagai M, Nagao K. Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis. Immunity. 2015 Apr 21;42(4):756-66. doi: 10.1016/j.immuni.2015.03.014. PMID: 25902485; PMCID: PMC4407815. Spittaels KJ, Ongena R, Zouboulis CC, Crabbé A, Coenye T. Cutibacterium acnes Phylotype I and II Strains Interact Differently With Human Skin Cells. Front Cell Infect Microbiol. 2020 Nov 16;10:575164. doi: 10.3389/fcimb.2020.575164. PMID: 33330124; PMCID: PMC7717938. Yu Y, Lu L, Sun J, Petrof EO, Claud EC. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model. Am J Physiol Gastrointest Liver Physiol. 2016 Sep 1;311(3):G521-32. doi: 10.1152/ajpgi.00022.2016. Epub 2016 Aug 4. PMID: 27492329; PMCID: PMC5076002.
- How can personalisation be used to develop products that maintain the microbiome?
Several industries have begun looking to the use of personalisation to improve the efficacy and targeting of their products or services. Cosmetic brands can embrace this practice when developing products that maintain the microbiome to improve customer satisfaction, and gain a competitive advantage while supporting and sustaining a healthy microbiome. Outline of research: A survey conducted on 1,038 adults in the U.S. found 75% of shoppers would pay more for a personalised shopping experience (Bolt, 2023) The personalised beauty space received 1.04 billion U.S. dollars worth of investment in 2021, its size is projected to increase to 63.34 billion dollars by 2027 (Statista 2021; GlobeNewswire, 2023) The skin microbiome varies across individuals, some of the factors include: age, sex, geographical location, and genetics (Russo et al., 2023; Kim et al., 2021; Robert et al., 2022; Gupta et al., 2017; Si et al., 2015; Wang et al., 2021) Use of certain skin care products can shift the microbiome away from its natural composition, giving rise to disorders like dermatitis by altering the microenvironments inhabited by these populations (Bouslimani et al., 2019) Microbiome personalisation can promote the use of formulations that prioritise fermented ingredients, extracts, ceramides, and prebiotics to nourish the good bacteria of the microbiome (Dolečková et al., 2020) Determining the specific microbiome composition of skin can be used to optimise products that help control or alleviate the symptoms of dysbiotic skin disorders through the inclusion of ingredients that reduce or prevent the growth of microbes driving these conditions (Collins 2023) Industry impact and potential: More brands are considering the importance of microbiome personalisation when formulating their products. Gallinee (an industry partner of Sequential) is one of the major drivers of this philosophy through their at-home microbiome testing kit that gives consumers an in-depth breakdown and report of their skin microbiome, allowing them to make detailed personalised choices regarding their skincare routines based on their microbiomes need. Our solution: We have partnered with several companies seeking to increase the level of personalisation for their products, including industry leaders such as Gallinée Microbiome Skincare and Shiseido, to provide Gold Standard Certification for your products. Our invivo microbiome testing platform and extensive database of 18,000+ samples provides a detailed assessment of how your product interacts with, and influences the skin microbiome, and other regions of the body like the scalp, mouth, and vaginal microbiome. We also provide formulation support for your personalised skin care products, ensuring its ingredients match the needs of what your product seeks to deliver. References: Bolt. (2023, May 31). 75% of shoppers would pay more for beauty products to get personalized online shopping experiences, says new survey. PR Newswire. Retrieved from https://www.prnewswire.com/news-releases/75-of-shoppers-would-pay-more-for-beauty-products-to-get-personalized-online-shopping-experiences-says-new-survey-301837863.html Bouslimani A, da Silva R, Kosciolek T, Janssen S, Callewaert C, Amir A, Dorrestein K, Melnik AV, Zaramela LS, Kim JN, Humphrey G, Schwartz T, Sanders K, Brennan C, Luzzatto-Knaan T, Ackermann G, McDonald D, Zengler K, Knight R, Dorrestein PC. The impact of skin care products on skin chemistry and microbiome dynamics. BMC Biol. 2019 Jun 12;17(1):47. doi: 10.1186/s12915-019-0660-6. PMID: 31189482; PMCID: PMC6560912. Collins SL, Stine JG, Bisanz JE, Okafor CD, Patterson AD. Bile acids and the gut microbiota: metabolic interactions and impacts on disease. Nat Rev Microbiol. 2023 Apr;21(4):236-247. doi: 10.1038/s41579-022-00805-x. Epub 2022 Oct 17. PMID: 36253479. Dolečková, Iva & Čápová, Aneta & Machková, Lenka & Moravčíková, Soňa & Marešová, Markéta & Velebný, Vladimír. (2020). Seasonal variations in the skin parameters of Caucasian women from Central Europe. Skin Research and Technology. 27. 10.1111/srt.12951. GlobeNewswire (2023). Global next-generation personalized beauty market to reach $63.34 billion by 2027 . Retrieved from https://www.globenewswire.com/fr/news-release/2023/07/04/2698923/0/en/Global-Next-Generation-Personalized-Beauty-Market-to-Reach-63-34-Billion-by-2027.html Gupta VK, Paul S, Dutta C. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity. Front Microbiol. 2017 Jun 23;8:1162. doi: 10.3389/fmicb.2017.01162. PMID: 28690602; PMCID: PMC5481955. Kim, JH., Son, SM., Park, H. et al. Taxonomic profiling of skin microbiome and correlation with clinical skin parameters in healthy Koreans. Sci Rep 11, 16269 (2021). https://doi.org/10.1038/s41598-021-95734-9 Robert C, Cascella F, Mellai M, Barizzone N, Mignone F, Massa N, Nobile V, Bona E. Influence of Sex on the Microbiota of the Human Face. Microorganisms . 2022; 10(12):2470. https://doi.org/10.3390/microorganisms10122470 Russo E, Di Gloria L, Cerboneschi M, Smeazzetto S, Baruzzi GP, Romano F, Ramazzotti M, Amedei A. Facial Skin Microbiome: Aging-Related Changes and Exploratory Functional Associations with Host Genetic Factors, a Pilot Study. Biomedicines. 2023 Feb 23;11(3):684. doi: 10.3390/biomedicines11030684. PMID: 36979663; PMCID: PMC10045008. Si J, Lee S, Park JM, Sung J, Ko G. Genetic associations and shared environmental effects on the skin microbiome of Korean twins. BMC Genomics. 2015 Nov 23;16:992. doi: 10.1186/s12864-015-2131-y. PMID: 26596276; PMCID: PMC4657342. Statista. (2021). Global investment in personalized beauty from 2010 to 2021 . https://www.statista.com/statistics/1268261/personalized-beauty-investment-worldwide/ Wang L, Xu YN, Chu CC, Jing Z, Chen Y, Zhang J, Pu M, Mi T, Du Y, Liang Z, Doraiswamy C, Zeng T, Wu J, Chen L. Facial Skin Microbiota-Mediated Host Response to Pollution Stress Revealed by Microbiome Networks of Individual. mSystems. 2021 Aug 31;6(4):e0031921. doi: 10.1128/mSystems.00319-21. Epub 2021 Jul 27. PMID: 34313461; PMCID: PMC8407115.
- What can algae-derived nutrients do for the skin?
Algae have been making waves recently as potential ingredients for use in the world of cosmetics, with many companies harnessing their natural abundance of bioactive compounds for use in formulating products. What we know: Algal pigments extracted from marine macroalgae (i.e., seaweed) confer antioxidant and photoprotective properties, plus antimicrobial, anti-inflammatory, and anti-ageing effects (Freitas et al., 2022; Kalasariya et al., 2022) Fucoidan extracts from seaweeds provide skin with anti-collagenase, anti-elastase and anti-atopic dermatitis properties, while essential and non-essential amino acids taken from algae improve collagen production, UV protection, and proteoglycan synthesis (Kalasariya et al., 2022) Fatty acids like eicosapentaenoic acid (EPA), arachidonic acid (AA), docosahexaenoic acid (DHA) act as emollients, enhance procollagen formation, and prevent inflammation (Kalasariya et al., 2022) Oligosaccharide-zinc complexes from Laminaria digitata affect structure and function of the skin’s microbiome by reducing sebum production to limit growth of bacteria like Cutibacterium acnes linked to skin conditions such as acne vulgaris (Jesumani et al., 2019) Ethyl acetate from Fucus evanescens promotes antibacterial activity against C. acnes and methicillin-resistant Staphylococcus aureus, a microbe that exacerbates skin conditions such as atopic dermatitis and psoriasis (Jesumani et al., 2019; David et al., 2017) Industry impact & potential: Companies have begun using extracts of algae in sunscreen and moisturiser formulations to promote protection from UVA and UVB radiation, photo-ageing, retention, skin gloss, and emollience in an alternative non-toxic manner to synthetic compounds. Many algal carrageenans (i.e., sulphated polysaccharide) have been used as additives for shampoo formulations to promote viscosity, freeze-thaw stability, and improve overall quality. The MareVitae® line owned by AlgaEnergy uses microalgae in their skin care products, with their patented Plankton7® extract containing active compounds from multiple algal species said to have individually beneficial effects on the face and skin. Other brands that have recently begun harnessing the power of algae and their extracts include Estée Lauder, ELEMIS, and Murad, with many citing anti-inflammatory, antioxidant and hydrating properties. Our Solution: There are challenges that must be addressed before algae can be used to their full potential, including strict regulatory controls to ensure they are safe for use. We provide bespoke testing services for novel cosmetic formulations, ensuring the impact they have on the physical, chemical and microbiomic characteristics of the skin is desirable. Once these restrictions have been met and overcome, there is little doubt that the full scope of algae’s capacity for both cosmetic and other industrial applications will be uncovered. References: David Wang, H-M., Li, X-C., Lee, D-J., Chang, J-S., Potential biomedical applications of marine algae, Bioresource Technology (2017), doi: http://dx.doi.org/10.1016/j.biortech.2017.05.198 Freitas MV, Pacheco D, Cotas J, Mouga T, Afonso C, Pereira L. Red Seaweed Pigments from a Biotechnological Perspective. Phycology . 2022; 2(1):1-29. https://doi.org/10.3390/phycology2010001 Jesumani V, Du H, Aslam M, Pei P, Huang N. Potential Use of Seaweed Bioactive Compounds in Skincare-A Review. Mar Drugs. 2019 Dec 6;17(12):688. doi: 10.3390/md17120688. PMID: 31817709; PMCID: PMC6950024. Kalasariya, Haresh & Pereira, Leonel. (2022). Dermo-Cosmetic Benefits of Marine Macroalgae-Derived Phenolic Compounds. Applied Sciences. 2022. 11954. 10.3390/app122311954.
- What is Conscious Beauty?
Conscious beauty is an emerging practice within the cosmetic space that places greater emphasis on the sustainability of a company and what it does to promote eco-friendly and ethical business practices, rather than its label or quick and easy-to-use ingredients. What we know: The clean beauty market is projected to increase up to $22 billion by 2024 (Statista, 2023), with skincare, haircare and cosmetics being the largest shareholders in the market. The global market value for natural cosmetics and skincare is expected to increase to roughly 59 billion dollars by 2031 (Statista, 2022). Consumer attitudes reflect market changes, with 43 percent of US millennials preferring natural skincare alternatives, and 55% of Gen Z respondents from the UK considering themselves ethical or sustainable consumers (Statista, 2023). Natural formulations help better nourish and feed the beneficial bacteria of the skin’s microbiome. E.g. Lactobacillus probiotics that secrete chemicals to prevent infection and inflammation, vitamin C that promotes a slightly acidic environment favoured by the skin’s microbiota, and ceramides that act as a food source for the microbes to promote skin health and vitality (Delanghe et al., 2021). Industry impact & potential: Companies that have embraced this philosophy of natural, organic and conscious beauty include: Neutrogena, Natura, and Dove, seen as the most sustainable beauty brand by the majority of Gen Z’s from Germany (51%), Brazil (70%), and the U.S. (54%), respectively. These brands emphasise ingredient transparency, cruelty free testing, reducing waste, and responsible sourcing of ingredients, actions that are favoured by a large proportion of the green consumer market. Our Solution: 77% of consumers state they would avoid buying products from brands found to be greenwashing or attempting to hide unsustainable business practices, highlighting the importance of honesty and transparency with consumers. (NIQ, 2023). Lack of ingredient transparency can negatively affect the skin by causing allergies and contact dermatitis, or even dysbiosis of the skin’s microbiome to trigger other conditions such as atopic dermatitis (eczema) and acne (Tran et al., 2022; Huang et al., 2023; Slomski 2022; Daniells 2023). Sequential has partnered with dozens of key players in the cosmetic market to help them deliver the high-quality products they promise their consumers. Our novel invivo microbiome testing platform, combined with our comprehensive microbiome database, is able to independently test and certify the quality of your product, making sure it meets consumer needs and expectations for skin health. We also offer a variety of personalised solutions to target areas of priority for your formulation, so you can make the most of your clean and natural brand. References: Daniells, Stephen. "Lactobio Q&A: ‘Products that focus on the skin microbiome could revolutionize the way we approach skin care’." Global Food , 2 Oct. 2023, p. NA. Gale OneFile: Health and Medicine , link.gale.com/apps/doc/A767533026/HRCA?u=anon~82f03388&sid=googleScholar&xid=6d46450c . Accessed 2 Aug. 2024. Delanghe L, Spacova I, Van Malderen J, Oerlemans E, Claes I, Lebeer S. The role of lactobacilli in inhibiting skin pathogens. Biochem Soc Trans. 2021 Apr 30;49(2):617-627. doi: 10.1042/BST20200329. PMID: 33704415. Huang, C., Zhuo, F., Han, B. et al. The updates and implications of cutaneous microbiota in acne. Cell Biosci 13 , 113 (2023). https://doi.org/10.1186/s13578-023-01072-w NIQ. (2023). Consumer behavior and greenwashing. NielsenIQ . Retrieved from https://nielseniq.com/global/en/insights/2023/consumer-behavior-and-greenwashing/ Slomski A. Postantibiotic Microbiome Therapeutic Reduces C difficile Recurrence. JAMA. 2022;327(12):1118. doi:10.1001/jama.2022.3753 Statista. (2022). Global market value for natural cosmetics and skincare from 2018 to 2031. Retrieved from https://www.statista.com/statistics/946788/natural-cosmetics-global-market-value/ Statista. (2023). Clean beauty market size worldwide in 2020 and 2024. Retrieved from https://www.statista.com/statistics/1095688/global-clean-beauty-market-size/ Tran J. M., Comstock J. R., Reeder M. J. (2022). Natural is not always better: The prevalence of allergenic ingredients in “clean” beauty products. Dermatitis , 33(3), 215–219. https://doi.org/10.1097/der.0000000000000863