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Bacterial vaginosis (BV) affects over half of women globally at some point in their lives, primarily due to a Lactobacillus -deficient vaginal microbiome. Despite this knowledge, there have been no significant advancements in effective BV treatments for nearly four decades, making this a critical area of research and interest. What We Know: BV is characterised by an imbalance in the vaginal microbiome, marked by a low abundance of beneficial Lactobacilli  and an overgrowth of diverse anaerobic bacteria. This imbalance leads to clinical symptoms such as discharge, odour and mucosal inflammation. BV is also linked to several adverse health outcomes, including preterm birth, infertility, cervical dysplasia and increased susceptibility to sexually transmitted infections (STIs), including HIV (Zhu et al., 2024) . Standard antibiotic treatments, like metronidazole (MTZ), often fail to provide lasting relief, with over 50% of patients experiencing recurrence within a year. This is partly because antibiotics tend to favour the growth of Lactobacillus iners  over Lactobacillus crispatus , the latter being associated with better health outcomes (Zhu et al., 2024) . Industry Impact and Potential: Recent research has shown that oleic acid (OA) and similar unsaturated long-chain fatty acids (uLCFAs) can inhibit L. iners  while simultaneously promoting the growth of L. crispatus.  These uLCFAs are essential for cell membranes and possess antimicrobial properties that suppress harmful microbes. Remarkably, OA has been found to encourage L. crispatus  dominance more effectively than traditional antibiotics in laboratory models of BV, suggesting a promising metabolite-based treatment approach (Zhu et al., 2024). Specific genes in non-iners Lactobacillus  species allow them to thrive in OA-rich environments. The gene farE  is crucial for OA resistance, while the enzyme ohyA helps these bacteria utilise OA for building their cell membranes. Importantly, treatments for BV that include OA - alone or in combination with metronidazole (MTZ) - enhance the growth of beneficial  L. crispatus  in lab studies. This research highlights different nutrient utilisation strategies among Lactobacillus  species and points to new approaches for improving women’s reproductive health (Zhu et al., 2024). Our Solution: At Sequential, we are at the forefront of microbiome research and development, offering comprehensive services beyond vaginal microbiome analysis. We also evaluate skin, scalp and oral microbiomes, establishing our leadership in testing products that maintain microbiome integrity. Our team of specialists excels in helping your company develop robust studies tailored to enhance the vaginal microbiome, promoting women's health and well-being. References: Zhu, M., Frank, M.W., Radka, C.D., Jeanfavre, S., Xu, J., et al. (2024) Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment. Cell . 187 (19), 5413-5430.e29. doi:10.1016/j.cell.2024.07.029.

Microplastics, the small plastic debris that result from the breakdown of consumer products and industrial waste, are widely recognised for their harmful environmental effects. However, little research has explored how these particles - which are found in up to 70% of cosmetic products - affect the skin microbiome. What We Know: Microplastics are tiny, solid plastic particles composed of polymers and additives. They are typically less than 5 mm and can be unintentionally formed through the wear and tear of larger plastic items (@European Chemicals Agency, 2024). These particles, including microbeads and fibres, are commonly found in personal care products like shower gels, toothpaste and nail polish and include polyethylene, polyethylene terephthalate and polypropylene. Microplastics serve various roles, from exfoliating beads in scrubs to enhancing product texture and stability, and even as glitter in makeup (Mim et al., 2024; Bashir et al., 2021). In Europe, it’s estimated that around 3800 tonnes of microplastics are released into the environment annually through everyday cosmetic and personal care products (@European Chemicals Agency, 2024). Microplastics can adsorb organic and inorganic contaminants on their surfaces, where biofilms may form, potentially acting as carriers of pathogenic vectors, pollutants, antimicrobial resistance, microorganisms and resistance genes. This raises concerns about how these particles may interact with the skin microbiome when present in cosmetic products (Mim et al., 2024).  Additionally, nanoplastics - smaller than microplastics, typically around 100 nm or less - can potentially penetrate biological barriers and may have toxic effects when present in topical products (Yong, Valiyaveettil & Tang, 2020). Industry Impact and Potential: Research on the impact of microplastics on the gut microbiome has shown that these particles can lead to significant shifts, including increased α-diversity and higher levels of potentially harmful pathobionts. As a result, it is widely hypothesised that microplastics may also be detrimental to the skin microbiome. However, further research is essential to elucidate the mechanisms behind these effects (Mim et al., 2024).  @Beat the Microbead is an innovative app developed by the @Plastic Soup Foundation that enables users to scan cosmetic product barcodes to check for microplastics. This empowers consumers to take control of their microplastic exposure and make informed choices, even before regulations and legislation fully address the issue. Our Solution: Sequential is a global leader in microbiome product development and testing, with locations in London, New York and Singapore. Our expertise and customisable services allow businesses to innovate confidently, ensuring their products preserve microbiome integrity and meet specific goals, such as efficacy, compatibility and environmental sustainability. References: Bashir, S.M., Kimiko, S., Mak, C.-W., Fang, J.K.-H. & Gonçalves, D. (2021) Personal Care and Cosmetic Products as a Potential Source of Environmental Contamination by Microplastics in a Densely Populated Asian City. Frontiers in Marine Science. 8. doi:10.3389/fmars.2021.683482. Mim, M.F., Sikder, M.H., Chowdhury, M.Z.H., Bhuiyan, A.-U.-A., Zinan, N. & Islam, S.M.N. (2024) The dynamic relationship between skin microbiomes and personal care products: A comprehensive review. Heliyon. 10 (14). doi:10.1016/j.heliyon.2024.e34549. Yong, C.Q.Y., Valiyaveettil, S. & Tang, B.L. (2020) Toxicity of Microplastics and Nanoplastics in Mammalian Systems. International Journal of Environmental Research and Public Health. 17 (5), 1509. doi:10.3390/ijerph17051509.

Every person’s skin is unique, shaped by genetics, the environment and lifestyle factors. Research demonstrates that personalised skincare, particularly when tailored to the skin microbiome, delivers more effective and lasting results by addressing each individual’s specific needs, promoting healthier and more resilient skin. What We Know: Human skin varies significantly due to genetic differences, which influence how it responds to environmental stressors, its susceptibility to ageing and its reactions to skincare products. These genetic variations are closely linked to factors like skin pigmentation, structure and sensitivity to UV radiation (Markiewicz & Idowu, 2018). Personalised skincare addresses these individual differences by tailoring products and treatments to each person's unique needs. This approach is gaining popularity in the cosmetics industry as it offers more effective and targeted solutions than generic skincare products. The primary benefits of personalised skincare include improved efficacy, as products are customised to match individual skin characteristics, and enhanced protection against environmental damage and ageing. By catering to the specific needs of different skin types, personalised skincare can also more effectively prevent or mitigate skin conditions (Markiewicz & Idowu, 2018). Industry Impact and Potential: A study that investigated the use of microbiome-tailored skincare products found that these products significantly enhanced skin health by supporting a more diverse and balanced skin microbiome. In the study, participants used microbiome-supporting (MS) products on one cheek and benchmark (BM) products on the other for three weeks. The results showed that the MS products led to a notable increase in beneficial bacterial diversity, reduced skin redness and improved skin texture. In contrast, the BM products only provided minor improvements in skin texture and did not significantly impact other skin health parameters (Santamaria et al., 2023). Parallel Health  uses whole genome sequencing to analyze an individual’s skin microbiome, creating customized phage-based skincare solutions. These serums target harmful bacteria causing issues like acne and rosacea while supporting beneficial microbes. The process includes a microbiome test, personalized consultations, ongoing skin assessments, and tailored serums for continuous skin health. Our Solution: Sequential's personalised skincare approach harnesses the power of microbiome-based facial products through its comprehensive Microbiome Product Testing Solution. This end-to-end service supports both independent testing and expert-guided formulation, enabling businesses to develop innovative, tailored skincare solutions that cater to individual microbiomes. References: Markiewicz, E. & Idowu, O.C. (2018) Personalized skincare: from molecular basis to clinical and commercial applications. Clinical, Cosmetic and Investigational Dermatology. 11, 161–171. doi:10.2147/CCID.S163799. Santamaria, E., Åkerström, U., Berger-Picard, N., Lataste, S. & Gillbro, J.M. (2023) Randomized comparative double-blind study assessing the difference between topically applied microbiome supporting skincare versus conventional skincare on the facial microbiome in correlation to biophysical skin parameters. International Journal of Cosmetic Science. 45 (1), 83–94. doi:10.1111/ics.12826.

Collagen is widely celebrated in the skincare industry for its anti-ageing and rejuvenating benefits. Recent research reveals that marine collagen peptides, used both orally and topically, support wound healing and may enhance skin health by modulating the skin microbiome. What we know: Collagen, the most abundant protein in the human body, comprises 30% of total protein content. Oral hydrolysed collagen boosts collagen peptides in the bloodstream, improving skin elasticity, hydration, and reducing water loss. Topically, it moisturizes the stratum corneum, reduces dryness and wrinkles, and enhances skin elasticity ( Gabriel Aguirre Alvarez  et al., 2020).  Skin wounds pose a major socio-economic challenge in healthcare. Treatments include collagen alginate dressings, silver sulfadiazine cream, autografts, allografts, and xenografts. Acellular fish skin (AFS) grafts have recently gained attention as a cost-effective option, acting as a 'skin substitute' that reduces inflammation and promotes pro-healing cytokines to improve wound recovery ( Hanna Luze  et al., 2022). The expression of nucleotide-binding oligomerization domain containing 2 (NOD2) and β-defensin (BD14) at the wound site directly affect the types of microorganisms that colonise wound (Mei et al., 2020). Industry impact and potential: A new xenograft technique utilising AFS grafts from Atlantic cod or Nile tilapia fish has shown promising results in wound healing. These grafts have demonstrated significant anti-inflammatory and antibacterial properties, which enhance the healing process for various types of wounds, including burns and DFUs. Current research is focused on comparing the effectiveness of fish skin grafts with other wound healing methods (Ibrahim et al., 2023). Research shows that oral collagen peptides from Atlantic salmon and Nile tilapia skin accelerate wound healing by upregulating NOD2 and BD14, key to immune response and skin repair. These peptides enhance collagen deposition, angiogenesis, and promote beneficial microbes like Leuconostoc and Enterococcus while suppressing harmful ones like Stenotrophomonas and Sphingomonas, improving overall wound healing outcomes (Mei et al., 2020). Products such as  ELEMIS  ‘Pro-Collagen Marine Cream’ and  Naturallythinking  ‘Marine Collagen Facial Cream’ are examples of topical approaches to utilising these beneficial collagen peptides. Further research into the benefits of topical and oral marine collagen for skin health, beyond wound healing, presents an exciting opportunity—especially in exploring its impact on the skin microbiome.  Our solution: Sequential provides a unique end-to-end microbiome product testing solution, complemented by specialised product development and formulation services. Leveraging our expertise, we assist businesses in creating innovative skin products, such as collagen-containing wound healing solutions, that preserve microbiome integrity and promote overall skin health. References: Aguirre-Cruz, G., León-López, A., Cruz-Gómez, V., Jiménez-Alvarado, R. & Aguirre-Álvarez, G. (2020) Collagen Hydrolysates for Skin Protection: Oral Administration and Topical Formulation. Antioxidants (Basel, Switzerland). 9 (2), 181. doi:10.3390/antiox9020181. Ibrahim, M., Ayyoubi, H.S., Alkhairi, L.A., Tabbaa, H., Elkins, I. & Narvel, R. (2023) Fish Skin Grafts Versus Alternative Wound Dressings in Wound Care: A Systematic Review of the Literature. Cureus. 15 (3), e36348. doi:10.7759/cureus.36348. Luze, H., Nischwitz, S.P., Smolle, C., Zrim, R. & Kamolz, L.-P. (2022) The Use of Acellular Fish Skin Grafts in Burn Wound Management-A Systematic Review. Medicina (Kaunas, Lithuania). 58 (7), 912. doi:10.3390/medicina58070912. Mei, F., Liu, J., Wu, J., Duan, Z., Chen, M., Meng, K., Chen, S., Shen, X., Xia, G. & Zhao, M. (2020) Collagen Peptides Isolated from Salmo salar and Tilapia nilotica Skin Accelerate Wound Healing by Altering Cutaneous Microbiome Colonization via Upregulated NOD2 and BD14. Journal of Agricultural and Food Chemistry. 68 (6), 1621–1633. doi:10.1021/acs.jafc.9b08002.

Scalp malodour is a significant concern, and unlike other body areas associated with unpleasant odour, there are currently no specific cosmetic or hygiene products designed to address it. Emerging research is shedding light on the role of the scalp microbiome in this issue, revealing how we can manipulate it to find effective solutions. What We Know: Body odour carries a strong social stigma around it and its psychological impact is not fully understood. Nevertheless, this olfactory cue is hypothesised to play a role in kinship detection and mate selection within human communities (Lam et al., 2018). Human body odour arises from bacterial decomposition of odourless sweat constituents like fatty acids and amino acids from eccrine, apocrine, and sebaceous glands. While Corynebacterium  species are linked to malodour at various body sites, research on the microbial causes of scalp malodour remains limited (James et al., 2013). Industry Impact and Potential: A study on body odour in prepubescent children and teenagers found that the mid-scalp region emits a distinct greasy odour, unlike the neck and underarms, which have a ‘sour+sulphur’ smell that shifts to primarily ‘sulphur’ after exercise. The mid-scalp consistently exhibits a dominant ‘sour’ odour, suggesting unique microbial metabolism in this area (Lam et al., 2018). Research suggests that the microbiome of the scalp is more stable compared to those of other areas of the body. This stability is attributed to the limited impact of showers on the scalp's microbial community and the presence of microbes residing in the hair follicles, which contribute to a more resilient and stable microbiome (Lam et al., 2018). A study found higher levels of Malassezia globosa  and  Cutibacterium acnes  in the scalp and neck compared to the underarms, with children’s scalps dominated by M. globosa  and teenagers’ by C. acnes , aligning with apocrine gland changes during puberty. However, no specific microbes were identified as linked to scalp malodour (Lam et al., 2018).  An additional study demonstrated that diacetyl (2,3-butanedione) is a major contributor to malodour of the scalp (Hara, Matsui & Shimizu, 2014). To truly unlock the potential of microbiome science in tackling scalp malodour, further research is essential. This exploration could revolutionise our approach to hair care, paving the way for innovative products that not only address but transform our understanding of scalp health.  Our Solution: With a database of 20,000 microbiome samples and 4,000 ingredients, along with a global network of 10,000 testing participants, Sequential offers customised solutions for microbiome studies and product formulation. Our dedication to creating products that maintain microbiome integrity make us the ideal partner for your scalp and hair care product development needs, including the exploration of malodour-addressing scalp care solutions. References: Hara, T., Matsui, H. & Shimizu, H. (2014) Suppression of Microbial Metabolic Pathways Inhibits the Generation of the Human Body Odor Component Diacetyl by Staphylococcus spp. PLOS ONE. 9 (11), e111833. doi:10.1371/journal.pone.0111833. James, A.G., Austin, C.J., Cox, D.S., Taylor, D. & Calvert, R. (2013) Microbiological and biochemical origins of human axillary odour. FEMS Microbiology Ecology. 83 (3), 527–540. doi:10.1111/1574-6941.12054. Lam, T.H., Verzotto, D., Brahma, P., Ng, A.H.Q., Hu, P., Schnell, D., Tiesman, J., Kong, R., Ton, T.M.U., Li, J., Ong, M., Lu, Y., Swaile, D., Liu, P., Liu, J. & Nagarajan, N. (2018) Understanding the microbial basis of body odor in pre-pubescent children and teenagers. Microbiome. 6 (1), 213. doi:10.1186/s40168-018-0588-z.

Introduction The human skin is constantly exposed to various environmental factors, with ultraviolet radiation (UVR) being a major influence on skin health and disease. UVR is divided into UVA, UVB, and UVC. Sunlight primarily consists of UVA (90–95%) and a smaller portion of UVB (5–10%), while UVC is almost entirely absorbed by the ozone layer and does not reach the Earth's surface (Rai, Rai & Kumar, 2022). Both UVB and UVA can lead to DNA damage, oxidative stress, premature aging, and an increased risk of skin cancer. Additionally, UVR has been linked to immune suppression and may significantly affect the skin’s microbiome. Hence, photoprotective measures are important to consider in order to protect the skin against the harmful effects of UVR (Grant, Kohil & Mohammad, 2024). Is UVR good or bad? UVR has several positive effects, including the activation of anti-inflammatory and immunosuppressive pathways, which benefit various skin conditions like psoriasis, atopic dermatitis, vitiligo, graft-versus-host disease, and can influence certain infections as UVR promotes vitamin D production, which may help reduce the risk of respiratory tract infections and tuberculosis (TB), with higher solar UVB exposure linked to lower TB incidence. UVR also enhances immune responses, such as macrophage activity and antimicrobial peptide production, which aid in combating infections (Hart et al ., 2019).  Beyond skin diseases, UVR also plays a beneficial role in systemic conditions such as asthma, multiple sclerosis, schizophrenia, type 1 diabetes, autism, and cardiovascular diseases. These effects result from interactions between UVR-induced regulatory cells and mediators like nitric oxide, interleukin-10, and 1,25-dihydroxy vitamin D3 (Rai, Rai & Kumar, 2022). Moderate exposure to UV radiation is also beneficial for health and plays a crucial role in the production of vitamin D (Xiaoyou et al ., 2024). Prolonged UVR exposure can generate reactive oxygen species (ROS) both directly by affecting cellular components and indirectly through photosensitization mechanisms. Indirectly produced ROS include various species such as superoxide anions (O2.-), singlet oxygen, hydroxyl radicals, and hydrogen peroxide, formed through different pathways. These free radicals can be further converted into other ROS types. Low ROS levels can cause mutations, medium levels may induce cellular senescence, and high levels typically lead to cell death, including apoptosis and necrosis (Figure 1) (Xiaoyou et al ., 2024). UVR damages DNA as well through two main mechanisms: direct and indirect. Direct damage, primarily from UVB rays, leads to the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts, which distort the DNA structure. Indirectly, UVA radiation generates reactive oxygen species (ROS) that oxidize DNA bases, causing mutations like 8-oxoguanine  (Figure 1) (Xiaoyou et al ., 2024). Both types of damage can impair DNA repair, leading to mutations, skin aging, and an increased risk of skin cancers.  Figure 1: UVR triggers the production of reactive oxygen species (ROS) and causes DNA damage. Chromophores absorb UV light, generating ROS such as superoxide anions (O2.-), singlet oxygen, hydroxyl radicals, and hydrogen peroxide through various pathways. UV-induced DNA damage primarily results in the formation of cyclobutane-pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PP), typically at dimerization sites. ROS can also contribute to single-strand breaks (SSBs) and double-strand breaks (DSBs) in DNA. Image taken from (Xiaoyou et al., 2024) . UV radiation (UVR) affects different age groups in distinct ways. Children generally face a lower risk of UV-related skin damage compared to adults. However, certain UV-induced conditions, such as photoaging (early skin wrinkling), freckles, and moles, can manifest during childhood and adolescence. Severe UV damage in early life may also increase the risk of long-term complications, including benign and malignant skin tumors, such as melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), later in adulthood (Green, Wallingford & McBride, 2011). In Japanese populations, the first sign of photoaging typically appears as solar lentigines on the face around the age of 20. This is followed by the development of fine wrinkles after 30, and benign skin tumors, like seborrhoeic keratoses, commonly appearing on sun-exposed skin after 35 (Ichihashi & Ando, 2014).  The response to UVR also varies with age at the cellular level. Younger skin has more efficient DNA repair mechanisms, while aging skin experiences increased DNA damage and impaired repair capacity due to the presence of senescent fibroblasts and reduced production of insulin-like growth factor-1 (IGF-1) (Kemp, Spandau & Travers, 2017). While UVR is essential for our health by aiding in vitamin D production and providing therapeutic benefits, excessive exposure poses serious risks. To enjoy the advantages of UVR while reducing its harmful effects, it’s crucial to implement preventive and protective measures. A key aspect of this understanding lies in recognizing the relationship between UV radiation and the skin microbiome. Skin Microbiome The human skin hosts a diverse array of bacteria, fungi, and viruses that form its microbiota. These microbes are crucial for maintaining skin homeostasis by protecting against pathogens, stimulating the immune system, and breaking down natural host products. Microbial populations are organized into complex communities that significantly influence the functionality of healthy skin. When the microbiota is disrupted, it can adversely affect the skin's immune homeostasis and contribute to systemic diseases (Willmott et al ., 2023). The skin primarily hosts four main bacterial phyla; Actinobacteria , Firmicutes , Proteobacteria , and Bacteroidetes . In moist regions, Staphylococcus  and Corynebacterium are the most prevalent. Oily areas tend to exhibit less diversity, with Cutibacterium  being the dominant species. In contrast, dry areas of the skin show the greatest diversity, consisting of a wide range of these four phyla (Smyth & Wilkinson, 2023). What is the relationship between UV and the Skin Microbiome As a unique ecosystem, human skin and its microbial inhabitants are also influenced by external environmental stressors, including UVR (Burns et al ., 2019). UVR can directly or indirectly affect the skin microbiome. Studies have shown changes in the composition of the skin microbiome, with different bacteria responding differently to UVA and UVB radiation (Gilaberte et al ., 2024). A study published in 2023 found significant changes in microbial beta diversity after four weeks of extensive sunlight exposure on the forearms of participants, compared to baseline measurements. Prior to taking a holiday in a sunny destination (minimum of 7 days duration), volunteers had skin swabs taken from their extensor forearm (d0), and upon their return, skin swabs were repeated at d1, d28, and d84. This suggests that sun exposure influences the diversity and composition of the skin microbiota (Willmott et al ., 2023). Additionally, the overall composition of the skin microbiome may be altered long-term following exposure to UVA and UVB radiation on the backs of the volunteers. Notable increases were observed in Cyanobacteria spp. , Fusobacteria spp. , Verrucomicrobia spp. , and Oxalobacteraceae spp.  In contrast, Lactobacillaceae spp.  and Pseudomonadaceae spp. decreased, with a more pronounced decline following UVA exposure (Burns et al ., 2019).  Research indicates that, similar to skin cells, bacteria respond differently to the UVA and UVB components of UVR. One study examining the effects of UVR on Pseudomonas aeruginosa  found that both UVA and UVB contribute to bacterial inactivation, shedding light on the vulnerability of specific microorganisms to UVR. Another study compared the responses of P. aeruginosa  to those of Escherichia coli  under similar conditions. While UVA significantly impacted the viability of P. aeruginosa , it had little to no observable effect on E. coli  (Smith et al ., 2023). UVR, Skin Microbiome, and Immune System Interaction The effects of UVR on the skin microbiome can occur through both direct and indirect mechanisms. UVR presents an immediate threat to both mammalian and microbial cells. Additionally, UVR can alter the microbial habitat of exposed skin, leading to further changes in the skin microbiome. One indirect mechanism involves the increased expression of antimicrobial peptides (AMPs) by the skin in response to UVR. Some species within the skin microbiome exhibit resistance to UVR, such as  Micrococcus luteus , which utilizes carotenoid pigments and has high endonuclease activity to counteract the otherwise bactericidal effects of UVR (Smith et al ., 2023). At sub-toxic levels, UVR can trigger a pathogen/damage-associated molecular pattern (PAMP/DAMP) response. This response may result in the release of microbial signals like oleic acid, lipopolysaccharides (LPS), and porphyrins, which can alter immune signaling and promote inflammation (Patra, Byrne & Wolf, 2016). Microbial metabolites can influence dendritic cells, aiding in the recognition and capture of pathogens. Additionally, microorganisms can produce natural antimicrobial peptides (AMPs) or regulate their production in keratinocytes, with UVR exposure potentially enhancing AMP levels. The UVR-induced cis-UCA may not only lead to an altered immune response but could also indirectly modify the microbial load by affecting the skin's microenvironment through unknown mechanisms. Furthermore, the microbiome can induce complement and interleukin-1 (IL-1) in response to UVR stress, influencing skin immunity through various cytokines, particularly in the Th17 pathway. Consequently, the production of IL-17 by keratinocytes may lead to changes in AMP production, creating a loop that ultimately affects the microbiome (Figure 2) (Patra, Byrne & Wolf, 2016). UVR can weaken the body's immune response to infectious microorganisms, potentially increasing the risk of microbial infections or elevating existing ones. This occurs as UVR induces dysbiosis, disrupting the natural balance of the skin microbiome and altering skin homeostasis. When the protective microbial community is compromised, harmful pathogens may thrive, leading to higher susceptibility to infections. Additionally, the changes in immune signaling pathways caused by UVR can impair the skin's ability to defend against these pathogens, further heightening the risk of skin-related infections and inflammatory conditions. Understanding this interplay emphasizes the importance of protecting the skin from excessive UV exposure to maintain both skin health and overall immune function (Gilaberte et al ., 2024). Figure 2:  Possible mechanisms microbes can influence UV-induced immune suppression. Image taken from (Patra, Byrne & Wolf, 2016) . Some fungi display photomorphogenic effects when exposed to UV light. A study found that increased doses of UV radiation reduced the production of porphyrins by Cutibacterium acnes , showing that these facial bacteria respond to UV exposure. They noted that C. acnes  reacted to UV-B at doses lower than 20 mJ/cm², even before any significant skin damage occurred (Wang et al ., 2012). Malassezia spp. , part of the normal skin flora, can cause pityriasis versicolor, a common skin condition mainly in tropical areas. At the typical sites of this condition, sunburn is rarely triggered. Malassezia furfur produces a UV-filtering compound known as pityriacitrin, which is believed to offer protective benefits. However, UVR is also known to suppress the cellular growth of  Malassezia furfur (Patra, Byrne & Wolf, 2016). Sunscreen, UV, and Skin Microbiome In recent years, effective sun protection strategies have been developed, emphasizing personalized approaches like wearing sun-protective clothing and using sunscreen. Modern sun protection products feature photostable, broad-spectrum UVA/UVB filters to protect against sunburn, skin cancer, photodermatoses, and photoaging. Many also include active ingredients that help prevent hyperpigmentation and premature skin aging, extending protection beyond just UV radiation (Schuetz et al ., 2024). There have been recent questions about how sunscreen affects the skin microbiome, though limited research is available. Nanoparticles like coated titanium dioxide (TiO₂) and zinc oxide (ZnO) in sunscreens have been shown to have antimicrobial effects, due to their ability to release metal ions and generate reactive oxygen species (ROS). The impact of these nanoparticles varies depending on the microorganism. Coated TiO₂ does not significantly affect skin bacteria growth, while UV exposure increases the bactericidal activity of uncoated ZnO. Most sunscreens use coated ZnO and TiO₂ particles, which are less harmful to bacteria (Grant et al ., 2024).  Factors like particle size, pH, preservatives, and added antimicrobial compounds in sunscreens may also influence the skin microbiome. Organic UV filters have been found to inhibit the growth of marine bacteria, fungi, and fish gut microbiota, but their direct effect on human skin bacteria is less known (Grant et al ., 2024). Study: Sunscreens can preserve human skin microbiome upon erythemal UV exposure (Schuetz et al ., 2024) In the above study they compared the effect of sunscreen SPF20 and placebo on UV exposed skin. Erythema was prominently observed in the unprotected areas, partially in the placebo treated zones, but was absent in the SPF20 treated areas, indicating effective photoprotection from the SPF (Schuetz et al ., 2024). The In vitro  results found that L. crispatus  was one of the most affected microbes when sunscreen was applied, showing a positive association with its abundance. In contrast, Cutibacterium acnes  did not show significant changes in its relative abundance. UV exposure reduced the ratio of  Lactobacillus  to Cutibacterium , indicating more Cutibacterium in those areas, while the sunscreen helped restore the original balance between these two types of bacteria (Schuetz et al ., 2024). L. crispatus  is common in the skin microbiome of younger individuals (18-35 yrs) and is also prevalent in the vaginal microbiome, playing an important role in women's health (Garlet et al ., 2024) (Schuetz et al ., 2024) (Argentini et al ., 2022).  Certain microorganisms, like L. crispatus , benefit from extra UV protection, as mentioned in the above clinical study. To confirm these results, they developed an in vitro model using individual bacteria and UV filters. They tested the survival of Lactobacillus crispatus , Cutibacterium acnes , and Staphylococcus epidermidis  under UV stress (Schuetz et al ., 2024). The results showed that specific UV filters, such as octocrylene and zinc oxide, improved the survival of L. crispatus  compared to the control. Combinations of these filters also protected L. crispatus , similar to the in vivo findings. However, some filters, like butyl methoxydibenzoylmethane, reduced the population of C. acnes , while maintaining or increasing S. epidermidis  levels. This suggests that choosing the right UV filters in sunscreens is very important (Figure 3) (Schuetz et al ., 2024). In conclusion, the above study provided valuable insights into the protective effects of an SPF 20 sunscreen on the skin microbiome after UV exposure. The findings highlight the relationship between UV radiation and the skin microbiome, emphasizing the importance of sun protection for maintaining healthy skin (Schuetz et al ., 2024). In the test, various UV filter formulations showed different effects on microbial survival. For example, some filters improved the survival of Lactobacillus crispatus , while others reduced Cutibacterium acnes  (Schuetz et al ., 2024). Despite limitations due to the small number of volunteers and sample variability, there results suggest that applying sunscreen before UV exposure can be beneficial for the skin microbiome. The researchers also believe that sunscreens with higher SPF values may offer even greater protection (Schuetz et al ., 2024). Lactobacillus crispatus , may help protect the skin and support its immune response, similar to its role in vaginal health. The ability of select UV filters to preserve beneficial bacteria while reducing harmful C. acnes  could lead to new skincare products aimed at protecting both skin and its microbiome from UV stress, enhancing overall skin resilience (Schuetz et al ., 2024). Figure 3: The survival rates of each microbial population four hours after exposure were calculated as a percentage compared to the initial population, with the relative protection provided by the UV filters expressed as a percentage. Image taken from (Schuetz et al., 2024) . Probiotics for Protecting Your Skin Microbiome from UV Damage  Probiotics are live microorganisms that provide health benefits to the host when consumed in sufficient amounts. Certain strains of lactic acid bacteria have been found to positively influence gut microbiota composition and metabolism, and in some cases, they can inhibit the growth of harmful bacteria. Research has shown a link between the gut-immune axis and skin health, with probiotic-rich foods helping to maintain skin balance and support the immune system (Souak et al ., 2021). Probiotics have also shown potential in protecting against UV-induced skin damage. For example, Lactobacillus johnsonii  NCC 533 (La1) has been found to help stabilize the skin's immune system by preventing UV-induced increases in interleukin-10 and reducing the recruitment of Langerhans cells. Similarly, Lactobacillus rhamnosus  GG (LGG) has been shown to prevent UV-related skin tumors due to its lipoteichoic acid (LTA), a component of gram-positive bacteria cell walls (Souak et al ., 2021).  Other potential probiotic candidates for photoprotection include Lactobacillus plantarum HY7714, Bifidobacterium breve , and Bifidobacterium longum  (Souak et al ., 2021). Conclusion In conclusion, protecting both the skin and its microbiome can help lower the risk of imbalances caused by UVR. Using sunscreens not only provides effective sun protection but also strengthens the skin barrier, which may help preserve a healthy microbiome by minimizing the penetration of harmful UV rays and environmental stress (Gilaberte et al ., 2024). More studies need to be done to understand how different wavelengths of UVR affect the skin microbiome, as well as the long-term impact of UVR on skin health, including its role in chronic conditions and aging. Additionally, further research is needed to explore how sunscreens influence the microbiome and more high-quality clinical studies are essential to confirm the potential of these approaches in safeguarding the skin microbiome from the effects of solar radiation (Gilaberte et al ., 2024). References Argentini C, Fontana F, Alessandri G, Lugli GA, Mancabelli L, Ossiprandi MC, van Sinderen  D, Ventura M, Milani C, Turroni F. Evaluation of Modulatory Activities of Lactobacillus crispatus Strains in the Context of the Vaginal Microbiota. Microbiol Spectr. 2022 Apr 27;10(2):e0273321. doi: 10.1128/spectrum.02733-21. Epub 2022 Mar 10. PMID: 35266820; PMCID: PMC9045136. Burns EM, Ahmed H, Isedeh PN, Kohli I, Van Der Pol W, Shaheen A, Muzaffar AF, Al-Sadek  C, Foy TM, Abdelgawwad MS, Huda S, Lim HW, Hamzavi I, Bae S, Morrow CD, Elmets CA, Yusuf N. Ultraviolet radiation, both UVA and UVB, influences the composition of the skin microbiome. Exp Dermatol. 2019 Feb;28(2):136-141. doi: 10.1111/exd.13854. Epub 2019 Jan 14. PMID: 30506967; PMCID: PMC7394481. Garlet A, Andre-Frei V, Del Bene N, Cameron HJ, Samuga A, Rawat V, Ternes P,  Leoty-Okombi S. Facial Skin Microbiome Composition and Functional Shift with Aging. Microorganisms. 2024 May 18;12(5):1021. doi: 10.3390/microorganisms12051021. PMID: 38792850; PMCID: PMC11124346. Gilaberte Y, Piquero-Casals J, Schalka S, Leone G, Brown A, Trullàs C, Jourdan E, Lim HW,  Krutmann J, Passeron T. Exploring the impact of solar radiation on skin microbiome to develop improved photoprotection strategies. Photochem Photobiol. 2024 May 20. doi: 10.1111/php.13962. Epub ahead of print. PMID: 38767119. Grant GJ, Kohli I, Mohammad TF. A narrative review of the impact of ultraviolet radiation and  sunscreen on the skin microbiome. Photodermatol Photoimmunol Photomed. 2024 Jan;40(1):e12943. doi: 10.1111/phpp.12943. PMID: 38288770. Green AC, Wallingford SC, McBride P. Childhood exposure to ultraviolet radiation and  harmful skin effects: epidemiological evidence. Prog Biophys Mol Biol. 2011 Dec;107(3):349-55. doi: 10.1016/j.pbiomolbio.2011.08.010. Epub 2011 Sep 3. PMID: 21907230; PMCID: PMC3409870. Hart PH, Norval M, Byrne SN, Rhodes LE. Exposure to Ultraviolet Radiation in the  Modulation of Human Diseases. Annu Rev Pathol. 2019 Jan 24;14:55-81. doi: 10.1146/annurev-pathmechdis-012418-012809. Epub 2018 Aug 20. PMID: 30125148. Ichihashi M, Ando H. The maximal cumulative solar UVB dose allowed to maintain healthy  and young skin and prevent premature photoaging. Exp Dermatol. 2014 Oct;23 Suppl 1:43-6. doi: 10.1111/exd.12393. PMID: 25234836. Kemp MG, Spandau DF, Travers JB. Impact of Age and Insulin-Like Growth Factor-1 on  DNA Damage Responses in UV-Irradiated Human Skin. Molecules. 2017 Feb 26;22(3):356. doi: 10.3390/molecules22030356. PMID: 28245638; PMCID: PMC5432641. Patra V, Byrne SN, Wolf P. The Skin Microbiome: Is It Affected by UV-induced Immune  Suppression? Front Microbiol. 2016 Aug 10;7:1235. doi: 10.3389/fmicb.2016.01235. PMID: 27559331; PMCID: PMC4979252. Rai S, Rai G, Kumar A. Eco-evolutionary impact of ultraviolet radiation (UVR) exposure on  microorganisms, with a special focus on our skin microbiome. Microbiol Res. 2022 Jul;260:127044. doi: 10.1016/j.micres.2022.127044. Epub 2022 Apr 21. PMID: 35483310. Schuetz R, Claypool J, Sfriso R, Vollhardt JH. Sunscreens can preserve human skin  microbiome upon erythemal UV exposure. Int J Cosmet Sci. 2024 Feb;46(1):71-84. doi: 10.1111/ics.12910. Epub 2023 Oct 6. PMID: 37664974. Smith, M. L., O’Neill, C. A., Dickinson, M. R., Chavan, B., & McBain, A. J. (2023). Exploring  associations between skin, the dermal microbiome, and ultraviolet radiation: advancing possibilities for next-generation sunscreens. Frontiers in Microbiomes , 2 , Article 1102315. https://doi.org/10.3389/frmbi.2023.1102315 Smythe P, Wilkinson HN. The Skin Microbiome: Current Landscape and Future  Opportunities. Int J Mol Sci. 2023 Feb 16;24(4):3950. doi: 10.3390/ijms24043950. PMID: 36835363; PMCID: PMC9963692. Souak D, Barreau M, Courtois A, André V, Duclairoir Poc C, Feuilloley MGJ, Gault M.  Challenging Cosmetic Innovation: The Skin Microbiota and Probiotics Protect the Skin from UV-Induced Damage. Microorganisms. 2021 Apr 27;9(5):936. doi: 10.3390/microorganisms9050936. PMID: 33925587; PMCID: PMC8145394. Wang Y, Zhu W, Shu M, Jiang Y, Gallo RL, Liu YT, Huang CM. The response of human skin  commensal bacteria as a reflection of UV radiation: UV-B decreases porphyrin production. PLoS One. 2012;7(10):e47798. doi: 10.1371/journal.pone.0047798. Epub 2012 Oct 25. PMID: 23133525; PMCID: PMC3485044. Willmott T, Campbell PM, Griffiths CEM, O'Connor C, Bell M, Watson REB, McBain AJ,  Langton AK. Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity. Front Aging. 2023 Aug 8;4:1217635. doi: 10.3389/fragi.2023.1217635. PMID: 37614517; PMCID: PMC10442491. Xiaoyou Tang, Tingyi Yang, Daojiang Yu, Hai Xiong, Shuyu Zhang, Current insights and  future perspectives of ultraviolet radiation (UV) exposure: Friends and foes to the skin and beyond the skin, Environment International, Volume 185, 2024, 108535, ISSN 0160-4120, https://doi.org/10.1016/j.envint.2024.108535 .

Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition characterized by recurrent, painful nodules and abscesses. It mainly affects areas of the body with skin folds, including the armpits, groin, and beneath the breasts. The impact of the condition goes beyond physical discomfort, such as associated pain, drainage, malodor, and scarring often result in significant negative psychosocial effects for those affected. Studies have revealed notable changes in the skin microbiome of individuals with HS, indicating a complex interaction between microbial communities and the disease's pathophysiology. What we know: HS patients exhibit an altered skin microbiome compared to healthy individuals. This dysbiosis is characterized by a reduction in microbial diversity and an overrepresentation of certain pathogenic bacteria (Lelonek et al ., 2023). Studies have found differences in specific bacterial taxa between HS patients and the control group. For instance, it was found that Mesorhizobium ,  Porphyromonas  and Peptoniphilus were more abundant in HS skin than healthy skin, and that Cutibacterium spp.  were decreased in HS patients (Lelonek et al ., 2023). An increased level of Gram-negative Porphyromonadaceae , Prevotellaceae , Fusobacteria , and Clostridales  in HS patients have also been noted​ (Luck et al ., 2022). The microbiota in various body sites of HS patients are less diverse and more similar to each other than in healthy individuals (Schneider et al ., 2020). In a study an increase in Finegoldia magna  in the groin and axilla of HS patients but a decrease in nasal swabs of these patients were observed (McCarthy et al ., 2022). Industry impact & potential: Non-obese HS patients have a different microbiome composition from obese ones, with subtle changes. More research is needed to understand these differences and their effects on the disease (Lelonek et al ., 2023). Microbiome research in HS could lead to new diagnostic tools and treatments. For example, profiling the microbiome might help identify those at risk for severe HS or predict how they will respond to treatments. Our solution: Sequential is a company specializing in skin microbiome testing, and we use advanced sequencing technologies to analyze skin microbial communities. We provide valuable insights into the microbiome profiles of individuals with HS or any skin conditions, helping to tailor personalized treatment. By partnering with dermatologists and researchers, we play a pivotal role in advancing microbiome-based diagnostics and therapeutics. Reference: Lelonek E, Bouazzi D, Jemec GBE, Szepietowski JC. Skin and Gut Microbiome in  Hidradenitis Suppurativa: A Systematic Review. Biomedicines. 2023 Aug 16;11(8):2277. doi: 10.3390/biomedicines11082277. PMID: 37626773; PMCID: PMC10452269. Luck ME, Tao J, Lake EP. The Skin and Gut Microbiome in Hidradenitis Suppurativa: Current  Understanding and Future Considerations for Research and Treatment. Am J Clin Dermatol. 2022 Nov;23(6):841-852. doi: 10.1007/s40257-022-00724-w. Epub 2022 Sep 18. PMID: 36116091. McCarthy S, Barrett M, Kirthi S, Pellanda P, Vlckova K, Tobin AM, Murphy M, Shanahan F,  O'Toole PW. Altered Skin and Gut Microbiome in Hidradenitis Suppurativa. J Invest Dermatol. 2022 Feb;142(2):459-468.e15. doi: 10.1016/j.jid.2021.05.036. Epub 2021 Aug 6. PMID: 34364884. Schneider AM, Cook LC, Zhan X, Banerjee K, Cong Z, Imamura-Kawasawa Y, Gettle SL,  Longenecker AL, Kirby JS, Nelson AM. Loss of Skin Microbial Diversity and Alteration of Bacterial Metabolic Function in Hidradenitis Suppurativa. J Invest Dermatol. 2020 Mar;140(3):716-720. doi: 10.1016/j.jid.2019.06.151. Epub 2019 Aug 27. PMID: 31465743.

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.

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.

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.

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.

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.