Pigmentation concerns are often treated as surface level issues, yet skin tone and dark spot formation are shaped by complex biological pathways. Traditional approaches tend to focus on single pathways or individual ingredients, but genetics, environment, metabolism and microbial activity all intersect and have impact. Multi-omics offers a more complete way to understand pigmentation by looking at multiple biological layers at once. This includes genes, proteins, metabolites, lipids and the skin microbiome. Bringing these insights together, this multi-omic view is shifting the field away from ingredient-led claims toward system-level insight into why pigmentation behaves differently across individuals and skin tones. What we know Multi-omic research shows that pigmentation outcomes emerge from interactions between genetic regulation, metabolic activity and intracellular signalling, with lipid and metabolite profiles playing a key role in pigmentation issues 1. Genetic, environmental and lifestyle factors interact to shape individual pigmentation responses 2. Since pigmentation pathways interact dynamically, focusing on one mechanism alone often fails to explain variable outcomes across skin tones, populations and environments 3. By integrating molecular, metabolic and microbial data, multi-omic approaches help explain why similar products can perform very differently between individuals 4. Industry impact and potential Multi-omics creates new possibilities for pigment care: Clearer understanding: Showing how and why pigmentation changes, not just whether it does. Better targeting: Designing formulas that target the biological processes most relevant to different pigmentation concerns. Inclusive innovation: Building products based on real biological differences across skin tones and environments, rather than one-size-fits-all averages. Our position At Sequential, we use multi-omic analysis to move pigmentation research beyond single-actives and surface outcomes. By integrating molecular, metabolomic and microbiome data with in-vivo testing, we map how pigmentation pathways respond over time and in real-world conditions. Supported by our 50,000+ sample database, this approach allows brands to develop evidence-led, inclusive pigment solutions grounded in biology rather than broad brightening claims. References Bajpai, V. et al. (2023). Determinants of human pigmentation. Science, 381, eade6289. Jablonski, N. (2021). Evolution of human skin pigmentation. Pigment Cell Melanoma Res, 34, 707–729. Pavan, W. & Sturm, R. (2019). Genetics of human skin and hair pigmentation. Annu Rev Genom Hum Genet, 20. Serre, C. et al. (2018). Regulation of human skin melanogenesis. Int J Cosmet Sci, 40.

Panthenol (pro-vitamin B5) is a widely used yet often underestimated skincare ingredient known for its soothing, hydrating and barrier-repair properties. Commonly found in creams, serums and masks, it is often seen as a supporting ingredient rather than a key active. However, evidence shows that panthenol does far more than basic moisturisation. For sensitive, compromised or post-procedure skin, it plays an important role in restoring comfort, resilience and skin function. As the industry shifts toward barrier health and gentle care, panthenol is increasingly recognised as a key ingredient for long-term skin recovery rather than short-term soothing. What we know Panthenol (provitamin B5) converts into pantothenic acid when applied to the skin and penetrates the outer skin layer, increasing water retention and reducing transepidermal water loss (TEWL) 1. It strengthens the skin barrier by supporting lipid production and new skin cell growth, helping damaged or irritated skin recover more quickly 2. Panthenol also has soothing and anti-inflammatory effects, helping to reduce redness, irritation and UV-related skin sensitivity 3. When used in skincare, 1–5% show consistent improvements in hydration, barrier repair and overall skin comfort 4. Industry impact and potential Panthenol offers clear opportunities for barrier-led, science-driven skincare innovation: Barrier-first formulations: Pairing panthenol with other ingredients such as ceramides and fatty acids to support barrier resilience. Sensitive and post-procedure care: Use in masks, emollients and recovery products for compromised or reactive skin. Synergistic systems: Combining with niacinamide or prebiotics to boost soothing, redness reduction and repair. Next-generation derivatives: Ingredients such as panthenol citrate potential for antioxidant, photoprotective and anti-inflammatory benefits. Our position At Sequential, we combine microbiome profiling with molecular, metabolomic and multi-omic analysis, and can evaluate how panthenol-containing formulations affect hydration, TEWL, lipid balance and skin resilience in real-world use. Leveraging our global database of 50,000+ samples, we support brands in developing evidence based, barrier-focused formulations that prioritise long-term skin health, comfort and repair rather than surface-level soothing claims alone. References Proksch, E. et al. (2017). Topical use of dexpanthenol: a 70th anniversary article. Journal of Dermatological Treatment, 28, 766–773. Gao, M. et al. (2025). Efficacy and safety of a panthenol-enriched mask for skin barrier recovery after facial laser treatment. Journal of Cosmetic Dermatology, 24. Gorski, J. et al. (2020). Dexpanthenol in wound healing after medical and cosmetic interventions. Pharmaceuticals, 13. Camargo, F. et al. (2011). Skin moisturizing effects of panthenol-based formulations. Journal of Cosmetic Science, 62, 361–370.

Bioferments are ingredients created through controlled fermentation, where selected microorganisms break down natural raw materials (e.g. rice or soy) into biologically active components. Although fermentation has long been used in food and medicine, its growing role in skincare reflects increasing demand for ingredients that are both effective and skin-compatible. As bioferments become more common, they are often grouped under a single label despite wide differences in production and skin behaviour, and the effects of fermentation are not always clearly defined. What we know Many bioferments act as postbiotic or prebiotic-like systems, supplying microbial metabolites that may support keratinocyte immunity and favour beneficial skin microbes 1. Fermentation can help enhance formulations’ ability to retain moisture, improving skin hydration and barrier support compared with non-fermented ingredients 2. In vitro and limited clinical studies suggest certain ferments can improve barrier metrics (e.g. hydration) and antioxidant capacity 3. Some bioferments show antimicrobial and anti-inflammatory activity in models, including reduced pro-inflammatory cytokines and inhibition of skin-relevant bacteria 4. Industry impact and potential Bioferments open up a rich area of exploration for skincare, offering both opportunity and challenge: Functional complexity: Single ingredients can deliver multiple bioactive components. Enhanced tolerability: Many bioferments are associated with good tolerability, making them appealing for sensitive or compromised skin. Mechanistic uncertainty: Many cosmetic ferments remain only partially characterised, creating opportunities to better understand how composition links to skin outcomes. Evidence gaps: More research is needed to understand how bioferments influence the microbiome and skin barrier over time. Our position At Sequential, we help brands move from “fermented” as a label to fermentation with purpose. Using microbiome profiling, metabolomics, molecular and multi-omic analysis alongside in-vivo testing, we characterise what bioferments actually contain and how they interact with skin biology over time. By linking composition to function, we provide mechanistic clarity, helping brands identify when fermentation genuinely improves performance, optimise formulations, and make defensible, evidence-led claims grounded in biology rather than buzzwords. References Yang, F. et al. (2025). Biologically active components and skincare benefits of rice fermentation products. Cosmetics, 12, 1–29 Majchrzak, W. et al. (2022). Biological and cosmetic importance of fermented raw materials. Molecules, 27, 4845. Cui, H. et al. (2023). Probiotic ferment lysate lotion improves skin barrier function. Sci Rep, 13, 43336. Nizioł-Łukaszewska, Z. et al. (2025). Apiaceae bioferments as sources of active skincare compounds. Molecules, 30, 983.

The skin lipidome is the complete collection of lipids naturally found within the skin, spanning the stratum corneum, viable epidermis and surface sebum. Often overlooked, lipids play a central role in skin function, regulating hydration, shaping responses to irritation and mediating interactions with the environment. While skincare often focuses on individual ingredients or surface-level effects, beneath this lies a highly organised lipid system that maintains barrier integrity, protects against environmental stressors and supports balance. Understanding the lipidome offers a different way to think about skin, as a system to understand and support. As skincare evolves, this shift is becoming key to moving beyond quick fixes towards more precise, long-term skin health. What we know The stratum corneum is built on a lipid matrix of ceramides, cholesterol and fatty acids that regulates water loss and protects against environmental stressors 1. Sebum adds triglycerides, squalene and wax esters, forming a surface film that supports flexibility and microbial balance 2. Lipids are bioactive. They drive inflammation, immune responses and pigmentation pathways 3. Lipid composition is dynamic, varying by site, age and condition, with small shifts linked to acne, eczema, dryness and ageing 4. Industry impact and potential The skin lipidome enables a shift from generic claims to biology-led innovation: Precision lipid design: Moving beyond simply “adding ceramides” to recreating the lipid profiles and ratios found in healthy skin. From replenishment to regulation: Addressing lipid imbalance and metabolism, rather than just replacing what is missing. Microbiome-aware formulations: Supporting beneficial microbes while limiting conditions that drive dysbiosis. Mechanism-led claims: Using lipidomics to demonstrate how formulations influence hundreds of lipid species. Our position At Sequential, we help brands move beyond surface-level measures of skin function by integrating lipidomics with microbiome and multi-omic analysis. By mapping how formulations shift the skin lipidome in real-world conditions, we enable targeted, evidence-led skincare that works with the skin’s biology. Using our global database of 50,000+ samples, we support the development of formulations that target the biological drivers of skin health, moving beyond short-term effects towards measurable, long-term outcomes. References Bouwstra, J, et al. (2023). The skin barrier: An extraordinary interface with an exceptional lipid organization. Prog Lipid Res, 92, 101252. Siqueira, R, et al. (2025). Skin Lipids and Their Influence on Skin Microbiome and Skin Care. ACS Omega, 10, 28534 - 28546. Nicolaou, A. et al. (2024). Bioactive lipids in the skin barrier mediate its functionality in health and disease. Pharmacol Ther, 260, 108681. Knox, S, et al. (2021). Skin Lipids in Health and Disease: A Review. Chem Phys Lipids, 236, 10505.

Most cosmetic brands want the same thing: faster launches, lower costs and stronger claims. But there is a costly mistake: choosing the cheapest available test and expecting it to support the biggest possible promise. The problem is not cheap testing. It is expecting evidence built for screening to prove outcomes it was never designed to measure. What does “cheap” cosmetic testing actually deliver? Low-cost testing provides valuable information during development. A package around £1,000 can determine whether a formulation remains stable, and whether it causes irritation under controlled conditions; however, such tests rarely demonstrate complex outcomes. They do not prove barrier improvement, microbiome restoration, reduced visible ageing or a clinically meaningful benefit. Why do underpowered studies fail? Claims require evidence that matches the promise. Many weak studies fail not because the study design cannot answer the question the claim requires. Problems often include small participant numbers, the absence of an appropriate control group, testing individual ingredients rather than the finished product, or extending conclusions beyond what was actually measured. The important thing is whether the evidence can withstand scrutiny from regulators, retailers and increasingly informed consumers. What happens when a claim is challenged? The cost of weak evidence is rarely limited to the testing fee. A challenged claim can require removal of advertising, delayed launches, additional studies and damage to retailer confidence. A £10,000 saving becomes a six-figure problem when a flagship claim fails. How does multi-omics compare on a cost-per-claim basis? Multi-omics is more expensive because it answers deeper questions: what changed, why it changed and whether those changes relate to consumer outcomes. For complex claims involving microbiome health or personalised skincare, it can strengthen evidence and reduce uncertainty. It does not replace clinical studies but helps explain the mechanisms behind observed effects. What price range buys regulator-defensible evidence? The right investment depends on the claim; there is no universal price for regulator-defensible evidence. Lower-risk claims may need only safety, stability and basic evaluation (£5,000–£20,000), while breakthrough claims involving microbiome modulation, anti-ageing or biological repair require stronger human evidence, objective measurements and potentially microbiome or biomarker analysis. Controlled human studies can start from £40,000. Where can brands legitimately save? Smart savings come from matching evidence investment to product risk. Brands can reduce unnecessary costs by using early screening approaches to refine formulations, eliminate weaker candidates before expensive studies begin, and focus deeper evidence generation on their most commercially important products. The mistake is spending less and expecting the evidence to prove more. The goal is to invest in the right evidence at the right stage.

The reality is, we are all aging. But what is the exact biological impact of this process on the skin? Modern longevity science has moved beyond surface-level aesthetics, mapping out precisely what happens at a cellular level as humans age [1]. For brands, formulators, and professionals in the dermatology and cosmetics space, understanding these biological root causes is essential for developing the next generation of scientifically-backed products [2]. The Biological Criteria for Aging Before exploring specific mechanisms, it is important to understand how scientists classify these biological processes. To be officially recognised as a "hallmark" of aging, a physiological process must meet three strict criteria [3]: Age-associated manifestation: The biological issue must clearly appear and progressively worsen as organisms get older. Acceleration by experimental accentuation: If intentionally triggered or worsened in a laboratory setting, it must cause rapid, accelerated physical aging. Opportunity for intervention: If a therapeutic or cosmetic treatment targets this specific problem, it must result in a measurable slowing or reversal of aging markers. The 12 Hallmarks of Aging: An Overview In 2013, the foundational "Hallmarks of Aging" were defined by researchers. Over the past decade, extensive scientific validation expanded this list, bringing the total to twelve fundamental processes in 2023 [3]: Fig 1. The Hallmarks Of Aging Deep Dive: 5 Crucial Mechanisms Driving Skin Aging For personal care and cosmetics formulation, certain biological hallmarks have a substantial impact on the skin's visible aging timeline. Here is a closer look at the five mechanisms that represent the frontier of longevity skincare. 1. Chronic Inflammation ("Inflammaging") What it is: "Inflammaging" is the result of long-lasting, low-level inflammation throughout the body. Over time, this constant state of stress makes it much harder for the skin to heal and renew itself [3,4]. Why it matters for skin: This causes the skin to break down its collagen and elastin, weaken its protective barrier, and heal much slower, directly leading to wrinkles, sagging, dryness, and an uneven tone. Fig 2. Inflamm-aging in the Skin 2. Dysbiosis What it is: Dysbiosis is a structural imbalance within the skin’s microbiome. In a healthy state, diverse populations of beneficial microorganisms coexist to protect the skin [5]. Why it matters for skin: As we age, our skin's physical composition undergoes significant changes that alter the "microenvironment" where these microbes live. This factor causes: Decreased Lipid Production: A reduction in natural oils (sebum) removes a primary nutrient source for beneficial bacteria. Diminished Hydration: Lower moisture levels create a drier, more difficult environment for microbes to survive. Barrier Fragility: A weakened physical defense layer makes the skin more susceptible to external stressors (like UV damage) and instability [6]. (fig. 3) Fig 3. Impact of the Skin Microbiome on Wrinkle Formation and Potential Modulation During Aging 3. Altered Intercellular Communication What it is: To stay healthy, the body's cells constantly send messages to each other. As you age, this communication breaks down, weakening the immune system and making it harder for the body to heal and protect itself [3]. Why it matters for skin: Healthy skin relies on different layers of cells talking to each other to produce collagen and keep the skin strong. When this communication breaks down, the skin struggles to heal or protect itself from sun damage, which leads to a weaker barrier and easier bruising [7]. 4. Loss of Proteostasis What it is: Proteostasis is the cells' recycling center, responsible for building and breaking down proteins (collagen, elastin and keratin). When it stops working properly, damaged proteins pile up and create a mass amount of toxic cellular waste [3]. Why it matters for skin: The buildup of this cellular waste creates an unhealthy environment that weakens the cells. As a result, the skin loses its natural radiance and its ability to remain firm and elastic [8]. 5. Epigenetic Alterations What it is: Picture DNA as the permanent blueprint of the body; the epigenome acts as the switches that turn specific genes on or off based on our environment and lifestyle. As we age, the mechanisms controlling these switches begin to fail, preventing genes from operating as efficiently as they did in youth [3]. Why it matters for skin: Rather than just being a symptom of getting older, shifts in the epigenome actively drive the skin's aging process. Fortunately, scientists can map these genetic switches to evaluate exactly how well certain topical treatments work, allowing us to see if a product can genuinely decelerate aging within the cells [9]. Where does Sequential fit in? Today, consumers demand "healthspan" and "skin longevity" products that target root biological causes rather than acting as temporary cosmetic fixes [12]. Targeting complex issues like chronic inflammation and microbiome imbalance requires highly advanced, active formulations. More importantly, regulatory bodies and modern consumers require strict, physiological proof of efficacy. Testing these advanced claims in standard petri dishes or skin models fails to capture the full interconnected picture of how we age on a biological level. This is where Sequential Bio steps in. Sequential's multi-omic platform integrates multiple layers of biological data to provide a holistic view of a formula’s performance: SNP Detection: Maps a consumer's unique DNA to reveal their natural baseline for skin aging, such as their likelihood to develop wrinkles. It helps predict how a consumer will respond to specific ingredients. This takes the guesswork out of formulation, empowering you to create highly personalized, science-backed product lines that you know will work. Microbial Gene Expression: Uncover how genes are activated in response to treatments. This gives in depth- insight into how the skin's surface reacts to your formulation. Proteomics: Measures the complete protein profile (elastin, keratin and collagen) of the skin to track how product impacts the cellular function and structural integrity. This gives you definitive proof that your product rebuilds and maintains the skin’s structure. By shifting away from simple observational studies and toward deep-level multi-omic biological validation, Sequential's multi-omic platform validates what's happening at the molecular level, giving personal care and dermocosmetic brands proof of biological mechanism; not just efficacy, but clear, and actionable data. The future of longevity skincare isn't about concealing age; it’s about biological validation. The focus has shifted to the mechanism of action. Consumers want to know what is happening at a molecular level: what is your product actually doing beyond the surface? References Haykal, D. et al. (2025) 'Advances in longevity: The intersection of regenerative medicine and cosmetic dermatology', Journal of Cosmetic Dermatology. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12268380/ (Accessed: 28 April 2026). Klinngam, W. et al. (2025) 'Longevity cosmeceuticals as the next frontier in cosmetic innovation: A scientific framework for substantiating product claims', Frontiers in Aging, 6. Available at: https://doi.org/10.3389/fragi.2025.1586999 (Accessed: 29 April 2026). López-Otín, C. et al. (2023) 'Hallmarks of aging: An expanding universe', Cell, 186(2), pp. 243-278. Available at: https://doi.org/10.1016/j.cell.2022.11.001 (Accessed: 29 April 2026). Gabriel, N. (2025) 'Inflammaging: How chronic inflammation accelerates visible aging', Ultimate Cosmetics. Available at: https://www.ultimatecosmetics.com.au/blog/inflammaging (Accessed: 28 April 2026). Borrego-Ruiz, A. and Borrego, J.J. (2024) 'Microbial dysbiosis in the skin microbiome and its psychological consequences', Microorganisms. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC11433878/ (Accessed: 28 April 2026). Challa, V. et al. (2025) 'Microbiome–aging–wrinkles axis of skin: Molecular insights and microbial interventions', International Journal of Molecular Sciences, 26(20), p. 10022. Available at: https://www.mdpi.com/1422-0067/26/20/10022 (Accessed: 28 April 2026). Lifespan.io (no date) Altered Intercellular Communication. Available at: https://lifespan.io/topic/altered-intercellular-communication/ (Accessed: 29 April 2026). Skin Organoids in Proteostasis Research: Early Insights into Aging (2025). Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC12961993/ (Accessed: 29 April 2026). Booth, L.N. and Brunet, A. (2016) 'The aging epigenome', Molecular Cell, 62(5), pp. 728-744. Available at: https://pubmed.ncbi.nlm.nih.gov/27259204/ (Accessed: 29 April 2026). Agrawal, R., Hu, A. and Bollag, W.B. (2023) 'The skin and inflamm-aging', Biology, 12(11), p. 1396. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC10669244/ (Accessed: 29 April 2026). Lancôme (2026) Lancôme Booklet. Available at: https://www.science.org/cms/asset/522c73c5-09e4-4279-96eb-8f764c08dc9c/_20260316_cpub_lancome_booklet.pdf (Accessed: 29 April 2026). Vogue (2026) 2026's biggest skincare trends to try now. Available at: https://www.vogue.com/article/2026s-biggest-skincare-trends-to-try-now (Accessed: 29 April 2026).

Tranexamic acid (TXA) has gained significant attention in skincare for its ability to treat hyperpigmentation by interrupting both pigment formation and pigment driven inflammation. Originally used medically to reduce bleeding, TXA inhibits plasma activity, a pathway recognised as relevant in pigment regulation. Its long clinical history means TXA enters cosmetic skincare with a stronger evidence base than many commonly used brightening ingredients. As its use grows, understanding how TXA performs within real formulations and on different skin types is essential for credible product development. What We Know: TXA (oral, intradermal and topical) improves melasma and other forms of hyperpigmentation, with significant reductions in MASI scores when compared to baseline or control (Calacattawi,et al, 2024). TXA decreases UV-induced melanocyte signalling, helping limit excess melanin production (Minasyan et al, 2024). TXA disrupts pigment transfer from melanocytes to keratinocytes, improving post-inflammatory hyperpigmentation (Chen et al, 2024). Topical TXA is well tolerated and can be paired with treatments such as microneedling, to enhance results, offering a safer alternative to stronger agents like hydroquinone (Konisky et al, 2023). Industry Impact and Potential: TXA’s multi-pathway action offers advantages for product development; Broad applicability -> Effective across varied pigmentation concerns including melasma, post inflammation hyperpigmentation and general uneven tone. Good tolerability -> Suitable for sensitive skin when formulated at low concentrations. Synergistic formulating -> Pairs well with niacinamide, vitamin C derivatives and retinoids for complementary pathways. Our Position: At Sequential, we help brands move from “TXA is trending” to “here is exactly what TXA is doing in this formula, on this skin.” We can help uncover what TXA is actually doing once it enters a full product system, how it interacts with other actives, whether it reaches relevant biological pathways, and how skin responds over time. Using our in-vivo testing frameworks, microbiome-aware models and multi-omic platforms, we can map changes in pigment biology, inflammation, and barrier behaviour . Our global database of 50,000+ samples allows us to benchmark TXA-containing formulations against diverse skin types, tones and real-world microbiome profiles, revealing who benefits most and why. References: Calacattawi, R. et al. (2024). Tranexamic acid for melasma: meta-analysis of RCTs. J Dermatol Treat, 35. Chen, T. et al. (2024). Tranexamic acid for hyperpigmentation disorders: an update. Clin Cosmet Investig Dermatol, 17, 2151–2163. Konisky, H. et al. (2023). Tranexamic acid in melasma: administration routes. J Cosmet Dermatol, 22, 1197–1206. Minasyan, M. et al. (2024). Oral tranexamic acid for PIH prevention and treatment. Dermatol Surg, 50, S219–S224.

Proteomics is the large-scale study of proteins, how they are expressed, modified and interact with the body. In skincare, proteomics is emerging as a powerful tool to understand how products influence skin function at a molecular level. Proteins play an important part in many skin processes and by analysing them, offers a more accurate picture of skin health, deeper than surface level observations alone. Unlike genomics, proteomics captures which proteins are present and active under specific conditions. What We Know: Proteomic analysis can identify shifts in structural proteins (e.g., keratin, filaggrin, collagen) associated with barrier strength and elasticity (Ma et al, 2020). Longitudinal proteomic monitoring reveals how products influence ageing pathways, including oxidative stress responses and collagen degradation (McCabe et al, 2020). Proteomics helps differentiate between short-term cosmetic effects and deeper, biologically meaningful changes (Benoit et al, 2023). Proteomics can be combined with microbiome data to show how protein changes relate to shifts in microbial activity, giving a clearer picture of overall skin health (Roux et al, 2021). Industry Impact and Potential: Proteomics opens new opportunities for product development; Targeted formulations:  By identifying protein level changes, more precise ingredient selection for specific skin concerns can occur. Personalised skincare:  Proteomic fingerprints may help tailor products to individual biological responses rather than general skin types. Credible product claims:  By combining proteomics with clinical endpoints, formulators can link specific protein changes directly to visible and functional outcomes. Our Position: At Sequential, we move beyond generic claims to generate clear, defensible evidence of biological impact. By integrating proteomic analysis with microbiome and multi-omic data from our global database of 50,000+ samples, we can determine exactly how formulations influence skin function over time. Our approach focuses on real-world evidence, quantifying changes in protein expression, barrier integrity and resilience, to support the development of products grounded in measurable outcomes rather than marketing terminology. References: Benoit, I. et al. (2023). A proteome-centric view of skin ageing and age-related pathways. Clin Cosmet Investig Dermatol, 16, 79–85. Ma, J. et al. (2020). Quantitative proteomics analysis of young and elderly skin. Aging (Albany NY), 12, 13529–13554. McCabe, M. et al. (2020). Alterations in extracellular matrix composition during ageing. Matrix Biology Plus, 8. Roux, P. et al. (2021). Integrative multi-omics reveals microbe–metabolite clusters linked to skin health. J Invest Dermatol.

For years, intimate care has relied on pH balancing as a measure of safety. However, pH alone does not protect vaginal ecosystems. Microbiome profiles differ widely between women based on hormones, ethnicity, contraceptive use, hygiene habits and life stage. Even pH-aligned products can still disrupt balance, reduce protective lactobacilli or slow recovery, leading to discomfort or recurring symptoms.   What We Know; Research highlights that: •      Vaginal microbiomes differ significantly between individuals and life stages, yet these variations can remain healthy (Condori-Catachura et al., 2025). •      Preservatives, surfactants and fragrance compounds can reduce lactobacillus dominance even when pH remains within recommended ranges (Han et al., 2021). •      Microbial recovery after disruption, particularly following antibiotic use or infection treatment, can take weeks  and with increased reoccurrence risks (Lehtoranta et al., 2020). •      “Gentle” or “pH-balanced” claims do not reliably protect against dysbiosis; true safety depends on strain-level preservation (Valeriano et al., 2024).   Industry Impact and Potential; Understanding these shifts means brands can now design products that better reflect real user needs: •      Lifecycle aligned solutions for key phases such as postpartum recovery, peri-menopause, or post-antibiotic care, where microbial disruption is most pronounced. •      More honest, evidence-based claims, moving beyond vague words like “gentle” or “pH-balanced” and focusing on real microbiome support. •      Clear guidance for users, helping people choose products that fit their unique microbiome or life stage, instead of assuming everyone needs the same thing.   Our Solution: Sequential evaluates how intimate-care products affect the vaginal microbiome in real use. Using qPCR, 16S, ITS and metagenomics, and drawing on a database of 50,000+ microbiome profiles, we measure effects on lactobacillus dominance, disruption and recovery over time. This evidence raises the standard for microbiome-safe intimate care, moving beyond pH-based claims toward solutions rooted in real biological protection.   References: Condori-Catachura, S. et al. (2025) Diversity in women and their vaginal microbiota. Trends in Microbiology, 33(11), 1163-1172. https://doi.org/10.1016/j.tim.2024.12.012 Han, Yet al., 2021. Role of Vaginal Microbiota Dysbiosis in Gynecological Diseases and the Potential Interventions. Frontiers in Microbiology, 12. https://doi.org/10.3389/fmicb.2021.643422 . Lehtoranta, L.,et al. (2020). Recovery of Vaginal Microbiota After Standard Treatment for Bacterial Vaginosis Infection: An Observational Study.  Microorganisms ,  8 (6), 875. https://doi.org/10.3390/microorganisms8060875 Valeriano, V., et al., 2024. Vaginal dysbiosis and the potential of vaginal microbiome-directed therapeutics. Frontiers in Microbiomes. https://doi.org/10.3389/frmbi.2024.1363089 .

City living exposes skin to constant, invisible stress such as pollutants, heavy metals and airborne microbes. This exposure changes the behaviour of the skin in terms of 1) how well it tolerates ingredients, 2) how quickly irritation appears, and 3) how long recovery takes after disruption. These changes are not just theoretical, research consistently shows measurable biological differences in pollution-exposed skin.   What We Know: Research demonstrates that continuous pollution exposure leads to measurable biological changes: •      Pollution alters microbial structure, reducing protective commensal species and favouring opportunistic organisms, leading to less stable microbial communities and increased reactivity (Yan et al, 2025). •      Airborne particulate matter drives lipid oxidation, producing inflammatory lipid metabolites that contribute to dullness and uneven tone, while also altering ingredient absorption and sensory feel (Araviiskaia, et al., 2019). •      Heavy metals disrupt immune signalling, prolonging recovery cycles and delaying restoration of hydration, transepidermal water loss and microbiome diversity after irritation or exfoliation (Misra, et al., 2021).   Industry Impact and Potential: This presents a great opportunity for brands to create produces which genuinely respond to urban skin stress, such as: •      Cleansers that remove pollutants without stripping beneficial microbes. •      Repair serums that protect lipids both dryness and oxidation. •      Ingredient combinations designed to reduce irritation and better support the skin barrier. •      Region-specific formulations tailored to pollution levels, humidity or season.   Our Solution: At Sequential we can quantify how pollution exposure alters microbial behaviour, lipid balance and recovery timelines using real-world testing. Through sequencing, biomarker profiling and multi-omic analysis, we can support you to compare urban vs non-urban responses, identifying disruption risks and resilience markers. With a global database of 50,000+ profiles across diverse climates and skin types, we help brands validate microbiome-safe formulations and turn environmental claims into measurable, defensible outcomes grounded in biological evidence.   References: Araviiskaia, E., et al. (2019). The impact of airborne pollution on skin. Journal of the European Academy of Dermatology and Venereology, 33, pp. 1496 - 1505. https://doi.org/10.1111/jdv.15583 . Misra, N., et al. (2021). Multi-omics analysis to decipher the molecular link between chronic exposure to pollution and human skin dysfunction. Scientific Reports, 11. https://doi.org/10.1038/s41598-021-97572-1 . Yan, D., et al. (2025). Particulate matter pollution alters the bacterial community structure on the human skin with enriching the Acinetobacter and Pseudomonas.. Ecotoxicology and environmental safety, 294, pp. 118061 . https://doi.org/10.1016/j.ecoenv.2025.118061 .

The gut and skin are connected through shared metabolic, immune and microbial pathways. When the gut microbiome becomes imbalanced, it can heighten systemic inflammation, worsening visible concerns such as acne, eczema, excess oil, redness and slow healing. Likewise, when the skin barrier is compromised, this can influence gut immune tolerance and increase reactivity to foods or environmental triggers. Rather than operating separately, gut and skin act as interacting ecosystems that influence each other’s stability.   What we know: Evidence shows that gut–skin interactions are measurable and biologically meaningful: •      Gut dysbiosis correlates with inflammatory skin conditions and slower recovery trajectories, meaning people with disrupted gut microbiota often experience more persistent or recurring flare-ups (Thye et al, 2022).    •      Probiotics can help the skin, but not everyone responds in the same way (Mahmud et al, 2022). •      Compounds produced in the gut can impact the skin’s oil levels, moisture, inflammation and repair processes (Jimenez-Sanchez, et al, 2025).   Industry impact and potential: Understanding the gut–skin connection gives brands an opportunity to move beyond surface-only products and address internal factors that influence skin balance. This enables more integrated inside–out solutions, rather than isolated topical treatments. This creates new possibilities such as: •      Paired ingestible-and-topical routines where supplements complement barrier-supportive skincare •      Bioactives that target internal flare triggers, such as probiotics or postbiotics used alongside barrier supportive skincare.   •      Timed product cycles   for specific skin stages, including barrier reset, seasonal dryness support, or dedicated acne management stages .   Our solution: Sequential enables brands to understand the gut-skin connection through real-world testing. Using cutting edge research techniques, we can track how changes in gut microbial composition translate into measurable shifts in skin outcomes. Using our global database of over 50,000 microbiome profiles, we are able to explore who responds, who doesn’t, and why. This insight sets a new standard for microbiome-informed skincare, moving beyond surface-only approaches and toward solutions grounded in the biology of the whole system.   References Jimenez-Sanchez, M., et al. (2025) The gut-skin axis: a bi-directional, microbiota-driven relationship with therapeutic potential.   https://doi.org/10.1080/19490976.2025.2473524 Mahmud , M. R., et al. (2022) Impact of gut microbiome on skin health: gut-skin axis observed through the lenses of therapeutics and skin diseases.   https://doi.org/10.1080/19490976.2022.2096995 Thye, A. Y-K., et al. (2022) Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis. https://doi.org/10.3390/biomedicines10051037

Introduction Periodontal disease arises from a disruption of the normal bacterial balance in the oral cavity, leading to chronic inflammation of the gingiva and, in advanced cases, irreversible damage to the supporting tissues of the teeth. Gingivitis, the early and reversible stage, affects a large proportion of adults worldwide and can progress to periodontitis if left unmanaged. Globally, periodontal disease represents a significant public health burden, contributing to disability, reduced quality of life, and substantial economic costs. Its development is closely linked to the accumulation of mature dental biofilms driven by inadequate oral hygiene, which promotes the overgrowth of pathogenic bacteria. Species such as Porphyromonas gingivalis , Tannerella forsythia , Fusobacterium nucleatum , Prevotella species, and Actinomyces  are consistently associated with disease onset and progression (Hu et al. , 2024). Given the central role of bacterial dysbiosis in periodontal disease, oral care products have been developed to target plaque accumulation and inflammation using ingredients with antimicrobial or modulatory properties, such as chlorhexidine, cetylpyridinium chloride, stannous fluoride, zinc salts, hydrogen peroxide, and prebiotic agents like arginine. While some of these ingredients demonstrate clear clinical benefits, particularly for gingivitis control, their precise effects on bacterial function and virulence remain incompletely understood. Emerging transcriptomic research suggests that different ingredients can selectively alter bacterial gene expression, influencing metabolic pathways, stress responses, and virulence-related mechanisms. A deeper understanding of how specific oral care ingredients affect pathogenic bacteria at the molecular level is therefore essential for the rational design of more effective formulations (Hu et al. , 2024). Article: The Effect of Oral Care Product Ingredients on Oral Pathogenic Bacteria Transcriptomics Through RNA-Seq (Hu et al.,  2024) The gene expression activity of six representative periodontal pathogenic bacteria: Actinomyces viscosus, Streptococcus mutans, Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella pallens  was measured using RNA sequencing (RNA-Seq) following exposure to nine common ingredients found in toothpaste and mouthwash, these being: stannous fluoride, stannous chloride, arginine bicarbonate, cetylpyridinium chloride, sodium monofluorophosphate, sodium fluoride, potassium nitrate, zinc phosphate, and hydrogen peroxide. This allows for an improved understanding of how individual oral care ingredients are able to influence bacterial activity, and allows for assessment of the effectiveness of each ingredient against the six bacterial species (Hu et al. , 2024). Results Analysis of the different treatments revealed stannous fluoride, stannous chloride, and hydrogen peroxide to have the most significant effects in reducing bacterial gene expression, with stannous chloride and hydrogen peroxide being among the most potent ingredients for inhibiting gene expression in all tested bacteria, and cetylpyridinium chloride reducing expression in almost all bacteria, with the exception of F. nucleatum . Inhibition of gene expression was significantly greater in the group receiving treatment with these ingredients compared to the no-treatment control group, indicating the effectiveness of these compounds in restricting bacterial growth and activity.  Transcriptomic analysis of bacterial gene expression found significant inhibition of the lipopolysaccharide (LPS) biosynthesis pathway in response to stannous chloride, stannous fluoride, and cetylpyridinium chloride use, with LPS molecules involved in bacterial cell membrane formation where they can act to trigger inflammation, tissue destruction, and bone loss associated with gingivitis and periodontal disease. These results indicate an ability of these compounds to work to downregulate bacterial genes associated with this pathway, and further restrict pathogen growth. Gene expression analysis also revealed a significant downregulation of infection-related genes in response to sodium fluoride, stannous chloride, and stannous fluoride, which has the effect of also reducing the virulence of the different bacteria. Bacterial degradation enzymes involved in the breakdown of host tissues and proteins to trigger inflammation and periodontal disease were also investigated via gene expression analysis. Results indicated a downregulation of these genes, particularly in response to stannous compounds, cetylpyridinium chloride, and sodium fluoride, with enzymes like hemolysin, which plays a role in red blood cell destruction and tissue damage, and collagenase, which allows bacteria to penetrate connective tissue and induce inflammation being significantly inhibited in response to these ingredients (Hu et al. , 2024). Conclusion The results of this study provide strong evidence to suggest the application of certain oral care product ingredients can significantly disrupt or alter the transcriptomic and metabolic activity of a variety of oral periodontopathogenic bacteria, with compounds like stannous fluoride, stannous chloride, and cetylpyridinium chloride being the most potent and players in triggering gene expression changes that lead to the inhibited growth and pathogenic activity of these bacteria, thus reducing their overall virulence and ability to trigger changes in the physical oral environment that induce progression of periodontal disease (Hu et al. , 2024). Strengths and Limitations of Research Strengths Allows for a more holistic discernment of how different chemical treatments can influence biological function by providing a community-wide perspective of how different microorganisms can respond to individual chemicals within oral care products rather than focusing on a single species or set of genes. By providing such a mechanistic understanding of these chemicals’ modes of action, it can allow for screening and ranking of ingredients for more efficient product formulations, as well as identifying compounds that hit different targets or different pathogens, further guiding product design (Hu et al. , 2024). Limitations Many of these studies still rely on 16S rRNA sequencing as a way to classify and determine compositional properties of the oral microbiome instead of high-throughput methods like shotgun metagenomic sequencing, limiting the resolution with which these microbial groups can be identified, and restricting the depth of functional gene analysis and exploration that can be achieved. This, therefore, limits the level of functional characterisation of oral biofilms that can be achieved using omics approaches (Xie et al. , 2025). Future Directions and Research Single-cell sequencing technologies can be implemented alongside existing multiomics approaches to enable the study of less abundant species of bacteria present within oral biofilms, as well as enabling targeted isolation and investigation of individual cell behaviors within complex microbial communities. This can provide further insight into health-disease markers associated with specific strains, and allow characterisation of the ecological profiles of previously unknown oral microbes and their response to various oral care products/formulations (Lin et al. , 2024). Conclusion Periodontal disease reflects a complex interplay between pathogenic bacteria, host responses, and environmental influences, with dysregulated microbial activity driving inflammation and tissue destruction. Growing evidence shows that oral care ingredients can influence not only bacterial survival but also key molecular pathways linked to virulence, immune activation, and tissue degradation. By modulating bacterial gene expression involved in processes such as endotoxin production, host tissue breakdown, and infection-related mechanisms, targeted formulations have the potential to reduce pathogenicity. Advancing molecular and multi-omics approaches offers a valuable framework for understanding these interactions at greater depth, supporting the development of more precise oral care strategies that better preserve oral health and help prevent disease progression. References Hu, P. et al.  (2024) ‘The Effect of Oral Care Product Ingredients on Oral Pathogenic Bacteria Transcriptomics Through RNA-Seq’, Microorganisms , 12(12), p. 2668. Available at:   https://doi.org/10.3390/microorganisms12122668 . Lin, Y. et al.  (2024) ‘Omics for deciphering oral microecology’, International Journal of Oral Science , 16(1), p. 2. Available at:   https://doi.org/10.1038/s41368-023-00264-x . Xie, Q. et al.  (2025) ‘Comprehensive Analysis of Orthodontic Treatment Effects on the Oral Microbiome, Metabolome, and Associated Health Indicators’, International Dental Journal , 75(3), pp. 1585–1598. Available at:   https://doi.org/10.1016/j.identj.2025.02.014 .