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Reproductive disorders affect millions of people worldwide. As we uncover more of the causative factors driving these diseases, including the potential role the vaginal microbiome plays, the better we can devise treatments to address and minimise the extent to which these issues affect and harm those that suffer from them.   What we know: Studies have shown vaginal microbiome composition to vary between those suffering from polycystic ovarian syndrome and healthy individuals, with PCOS patient composition consisting of pathogenic bacterial species linked to diseases such as bacterial vaginosis (BV), and a reduced prevalence of beneficial Lactobacillus which helps to defend against infection (Tu et al., 2020) Findings suggest vaginal microbiome transplants from healthy individuals have potential to alleviate symptoms of reproductive disorders like endometriosis by repopulating the dysbiotic space with a healthy vaginome and reducing the presence of symptoms associated with these conditions such as endometriotic lesions and inflammation (Lu et al., 2022) Individuals with infertility are more likely to possess greater amounts of BV-associated bacteria characteristic of asymptomatic vaginosis and a lower amount of lactobacilli than non-infertile counterparts. The general vaginome composition also varies, with Candida & Enterococcus species being more prevalent in people with infertility, while healthy vaginas were dominated with Lactobacillus (Babu et al., 2017) Vaginal microbiome dysbiosis has also been linked to cervical cancer. This is due to a prolonged exposure to a pathogenic environment that increase patient susceptibility to disorders such as aerobic vaginitis, chlamydia and BV, which may be associated with cervical carcinogenesis (Sekaran et al., 2023)   Industry impact & potential: As more awareness is raised regarding reproductive health, many companies in the healthcare market are making use of microbiome science to devise treatments for these conditions. LUCA Biologics is seeking to develop microbiota-based solutions for microbiome restoration to treat disorders associated with is imbalance including preterm birth (PTB). Freya Biosciences is an emergent start-up utilising microbial immunotherapies to treat conditions such as infertility & endometriosis associated with a dysbiotic microbiome.   Our solution: At Sequential, we have built a team of scientists who have spent the past 5 years studying the human microbiome carefully. We have advisors on our team, like Professor Phillip Bennett, who is a world leader in vaginal microbiome and pre-term birth. We have worked with over 60 clients globally, and we’re ready to work with your company on intimate female health applications, microbiome testing, an invivo and clinical certification, and formulation support. References: Babu G, Singaravelu BG, Srikumar R, Reddy SV, Kokan A. Comparative Study on the Vaginal Flora and Incidence of Asymptomatic Vaginosis among Healthy Women and in Women with Infertility Problems of Reproductive Age. J Clin Diagn Res. 2017 Aug;11(8):DC18-DC22. doi: 10.7860/JCDR/2017/28296.10417. Epub 2017 Aug 1. PMID: 28969122; PMCID: PMC5620762. Lu F, Wei J, Zhong Y, Feng Y, Ma B, Xiong Y, Wei K, Tan B, Chen T. Antibiotic Therapy and Vaginal Microbiota Transplantation Reduce Endometriosis Disease Progression in Female Mice via  NF-κB Signaling Pathway. Front Med (Lausanne). 2022 Mar 30;9:831115. doi: 10.3389/fmed.2022.831115. PMID: 35433736; PMCID: PMC9005645. Sekaran K, Varghese RP, Gopikrishnan M, Alsamman AM, El Allali A, Zayed H, Doss C GP. Unraveling the Dysbiosis of Vaginal Microbiome to Understand Cervical Cancer Disease Etiology-An Explainable AI Approach. Genes (Basel). 2023 Apr 18;14(4):936. doi: 10.3390/genes14040936. PMID: 37107694; PMCID: PMC10137380. Tu Y, Zheng G, Ding G, Wu Y, Xi J, Ge Y, Gu H, Wang Y, Sheng J, Liu X, Jin L, Huang H. Comparative Analysis of Lower Genital Tract Microbiome Between PCOS and Healthy Women. Front Physiol. 2020 Sep 8;11:1108. doi: 10.3389/fphys.2020.01108. Erratum in: Front Physiol. 2021 Jan 18;11:635088. doi: 10.3389/fphys.2020.635088. PMID: 33013474; PMCID: PMC7506141.

Acne is a prevalent and multifactorial skin disease affecting teenagers and adults, generally stemming from an imbalance in the skin microbiome. Studies have shown that various essential oils (EOs) possess antimicrobial properties that can inhibit the growth of acne-causing bacteria strains like Cutibacterium acnes and Staphylococcus epidermidis. What we know: Current acne treatments often involve topical or oral antibiotics, raising concerns about antibiotic resistance in C. acnes strains (Sardana et al., 2015). EOs are natural, concentrated liquids derived from plants, known for their aromatic properties and diverse biological characteristics, including bactericidal, virucidal and fungicidal properties (Cossetin et al., 2021). These include oregano, lavender, lemon grass, myrtle, lemon, thyme, eucalyptus, rosemary and tea tree EOs, which have all demonstrated anti-inflammatory, antioxidant and antimicrobial properties (Bungau et al., 2023). EOs are able to permeate the skin and facilitate the enhanced penetration of active compounds into deeper skin layers (Bungau et al., 2023). Their antimicrobial property occurs as their bioactive components target multiple cellular sites and interact with cell membranes, disrupting microbial integrity and ultimately causing cell death (Bungau et al., 2023). Industry Impact Incorporating English lavender and peppermint EOs into gelatine nanofibers created effective topical patches for localised acne treatment by diminishing C. acnes and S. epidermidis (Uhlířová et al., 2023). Therefore, English lavender and peppermint EOs may be beneficial in the gentle and focused treatment of acne, as well as potentially other microbial-related skin conditions (Uhlířová et al., 2023). However, a challenge with EO use is their standardisation, which arises due to different cultivation conditions that produce EOs of varied quality, quantity & composition (Uhlířová et al., 2023). Methods for assessing antioxidant potential, such as determining total phenolic content, evaluating reducing power, measuring ferrous ion chelating activity, among other methods, are vital for gauging the efficacy & safety of essential oil use in acne treatment (Bungau et al., 2023). Future investigations could focus on developing innovative acne treatments incorporating essential oils & evaluating their effectiveness through large-scale clinical trials. More research is warranted to elucidate the mechanisms of action of essential oils & identify their optimal doses & safety profiles for effective management of acne vulgaris (Bungau et al., 2023). Our Solution: At Sequential, we offer a comprehensive Microbiome Product Testing Solution, separately or in conjunction with guided product development & formulation services. This holistic approach enables your business to explore innovative methods for addressing conditions, like acne, using essential oils treatment strategies. References: Bungau AF, Radu AF, Bungau SG, Vesa CM, Tit DM, Purza AL, Endres LM. Emerging Insights into the Applicability of Essential Oils in the Management of Acne Vulgaris. Molecules. 2023 Sep 1;28(17):6395. doi: 10.3390/molecules28176395. PMID: 37687224; PMCID: PMC10489792. Cossetin LF, Santi EMT, Garlet QI, Matos AFIM, De Souza TP, Loebens L, Heinzmann BM, Monteiro SG. Comparing the efficacy of nutmeg essential oil and a chemical pesticide against Musca domestica and Chrysomya albiceps for selecting a new insecticide agent against synantropic vectors. Exp Parasitol. 2021 Jun;225:108104. doi: 10.1016/j.exppara.2021.108104. Epub 2021 Apr 1. PMID: 33812979. Sardana K, Gupta T, Garg VK, Ghunawat S. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management. Expert Rev Anti Infect Ther. 2015 Jul;13(7):883-96. doi: 10.1586/14787210.2015.1040765. Epub 2015 May 29. PMID: 26025191. Uhlířová R, Langová D, Bendová A, Gross M, Skoumalová P, Márová I. Antimicrobial Activity of Gelatin Nanofibers Enriched by Essential Oils against Cutibacterium acnes  and Staphylococcus epidermidis . Nanomaterials (Basel). 2023 Feb 24;13(5):844. doi: 10.3390/nano13050844. PMID: 36903722; PMCID: PMC10005654.

Fertility factors & vaginal microbiome:  Researchers conducted 16S rRNA sequencing on samples from 85 participants (xu et al., 2020) Age and elevated estradiol was linked to increased Streptococcus agalactiae High basal E2 correlated with reduced Lactobacillus iners and Lactobacillus plantarum  Escherichia coli was found to be higher in women with tubal obstruction, prolonged menstrual cycles, and elevated antral follicle count  Prevotella intermedia and unclassified Shewanella were also found to be linked to tubal obstruction Specific bacteria (Escherichia coli, Streptococcus agalactiae) were found to be potential biomarkers for reproductive health Factors in human production:  One study aimed to explore lifestyle, nutrition, and epigenetics (D’Argenio et al., 2021)  It was found that lifestyle elements including activity, stress and sleep can impact fertility  It was also found that nutrition including folate, vitamin D and antioxidant intake influences the success of IVF Genital microbiome & infertility:  Imbalance of Lactobacilli, especially Lactobacillus crispatus, has been linked to infertility and can negatively impact on assisted reproductive treatments (Vitale et al., 2021) Escherichia coli was linked to primary infertility  Ureaplasma and Garnerella vaginalis were both linked to bacterial vaginosis which is also thought to negatively affect fertility  Lack and Lactobacillus in endometrium was associated with embryo implantation difficulties which could be further hindered by an imbalance of the cervix microbiome Vaginal microbiota & pregnancy:  A study of 2,313 pregnant women identified Lactobacillus crispatus as protective, reducing diversity and adverse outcomes (Baud et al., 2023)  They also found that lower Lactobacillus was linked to higher diversity and increased preterm delivery risks  Gardnerella vaginalis was also associated with diverse community states.  They observed co-occurrence variations with Candida albicans and Ureaplasma species At Sequential: Our Scientific Advisor Professor Phillip Bennett has been one of the key pioneers in researching the vaginal microbiome. In particular, to understand and characterise the impact of the vaginal microbiome on preterm labour. The delicate balance of the vaginal microbiome can be thrown off if incorrect intimate care products are used atop of it resulting in unwanted conditions. Sequential has made it its mission to uncover the true impact of formulations on the microbiome across varying human conditions (bacterial vaginosis, etc.). At present, our database of over 18,000 human microbiome samples is one of the most sophisticated within the industry. References: Baud, A., Hillion, KH., Plainvert, C. et al.  Microbial diversity in the vaginal microbiota and its link to pregnancy outcomes. Sci Rep  13, 9061 (2023). https://doi.org/10.1038/s41598-023-36126-z D’Argenio V, Dittfeld L, Lazzeri P, Tomaiuolo R, Tasciotti E. Unraveling the Balance between Genes, Microbes, Lifestyle and the Environment to Improve Healthy Reproduction. Genes . 2021; 12(4):605. https://doi.org/10.3390/genes12040605 Vitale SG, Ferrari F, Ciebiera M, Zgliczyńska M, Rapisarda AMC, Vecchio GM, Pino A, Angelico G, Knafel A, Riemma G, et al. The Role of Genital Tract Microbiome in Fertility: A Systematic Review. International Journal of Molecular Sciences . 2022; 23(1):180. https://doi.org/10.3390/ijms23010180 Xu J, Bian G, Zheng M, Lu G, Chan WY, Li W, Yang K, Chen ZJ, Du Y. Fertility factors affect the vaginal microbiome in women of reproductive age. Am J Reprod Immunol. 2020 Apr;83(4):e13220. doi: 10.1111/aji.13220. Epub 2020 Jan 21. PMID: 31925865; PMCID: PMC7078941.

Psoriasis is a chronic autoimmune disease that affects up to 3% of people globally (Chen et al 2020). It can cause dry & flaky lesions on the skin and much discomfort to those that possess this disorder. The microbiome has been found to have dysbiotic effects on onset and progression, and its treatment can help alleviate the symptoms of this condition.   What we know: Colonisation of the skin by certain pathogens has been associated with the onset or exacerbation of psoriasis lesions, including Staphylococcus aureus, Malassezia, and Candida albicans that are able to trigger cutaneous inflammatory responses through the secretion of microbial toxins and superantigenic factors (Fry & Baker, 2007) Psoriatic skin lesions have been found to possess greater levels of alpha diversity and heterogeneity compared to healthy controls, with psoriatic skin being enriched for Staphylococcus aureus & Staphylococcus pettenkoferi and healthy skin possessing more Staphylococcus epidermidis & Cutibacterium acnes (Chang et al 2018) The skin mycobiome has also been found as being more diverse in psoriatic skin compared to healthy controls, with non-Malassezia species making up 68.0% in patients with psoriasis compared to only 39.4% in controls (Takemoto et al 2014) Wounds created by itching of psoriatic lesions can push epidermal bacteria further into the deep dermis or bloodstream to trigger an inflammatory response upon interaction with immune cells that can push the skin further into dysbiosis (Celoria et al 2023) Probiotics have been considered a viable treatment for treating this disorder, with probiotic Lactobacillus pentosus administration reducing the level of erythema, scaling, and epidermal thickening of psoriatic mouse skin models compared to untreated controls (Chen et al 2017)   Industry impact & potential: While many psoriasis-specific microbiome solutions have yet to be invented by cosmetic brands, some have devised a way to address the symptoms of this condition by working with the skin’s natural microbiota to promote health and modulation. AxisBiotix Ltd has invented a live oral probiotic supplement that works with the body’s gut-skin axis to reduce the symptoms & appearance of psoriatic skin lesions. Link to Sequential: Sequential is an industry leader in skin microbiome testing solutions, where we offer an extensive range of models (skin, vagina/vulva, scalp, oral) for you to test the effects of your formulation on. If your brand is interested in investigating psoriasis, the microbiome, or other important biological endpoints, we offer end-to-end invivo microbiome testing, clinical measurements, as well as expert formulation advice to guide and support your product development. References: Celoria V, Rosset F, Pala V, Dapavo P, Ribero S, Quaglino P, Mastorino L. The Skin Microbiome and Its Role in Psoriasis: A Review. Psoriasis (Auckl). 2023 Oct 26;13:71-78. doi: 10.2147/PTT.S328439. PMID: 37908308; PMCID: PMC10614657. Chang HW, Yan D, Singh R, Liu J, Lu X, Ucmak D, Lee K, Afifi L, Fadrosh D, Leech J, Vasquez KS, Lowe MM, Rosenblum MD, Scharschmidt TC, Lynch SV, Liao W. Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization. Microbiome. 2018 Sep 5;6(1):154. doi: 10.1186/s40168-018-0533-1. PMID: 30185226; PMCID: PMC6125946. Chen L, Li J, Zhu W, Kuang Y, Liu T, Zhang W, Chen X, Peng C. Skin and Gut Microbiome in Psoriasis: Gaining Insight Into the Pathophysiology of It and Finding Novel Therapeutic Strategies. Front Microbiol. 2020 Dec 15;11:589726. doi: 10.3389/fmicb.2020.589726. PMID: 33384669; PMCID: PMC7769758. Chen YH, Wu CS, Chao YH, Lin CC, Tsai HY, Li YR, Chen YZ, Tsai WH, Chen YK. Lactobacillus pentosus GMNL-77 inhibits skin lesions in imiquimod-induced psoriasis-like mice. J Food Drug Anal. 2017 Jul;25(3):559-566. doi: 10.1016/j.jfda.2016.06.003. Epub 2016 Aug 5. PMID: 28911642; PMCID: PMC9328808. Fry L, Baker BS. Triggering psoriasis: the role of infections and medications. Clin Dermatol. 2007 Nov-Dec;25(6):606-15. doi: 10.1016/j.clindermatol.2007.08.015. PMID: 18021899. Takemoto, Akemi & Cho, Otomi & Morohoshi, Yuka & Sugita, Takashi & Muto, Masahiko. (2014). Molecular characterization of the skin fungal microbiome in patients with psoriasis. The Journal of Dermatology. 42. 10.1111/1346-8138.12739.

Microbiome engineering is cutting-edge technology involving colonisation of the skin with microbes engineered to serve specific functions. These fast-growing and adaptable microbes may act as therapeutics to treat skin conditions by working with the skin’s natural biology to deliver effective treatments for aesthetic and medical dermatological purposes.   What we know: A group of researchers engineered Cutibacterium acnes to secrete NGAL, a protein capable of reducing sebum production in skin by triggering destruction of sebocytes, with twofold reduction in sebocyte density observed after 48 hours (Knödlseder et al., 2024) Engineered live strains of Staphylococcus epidermidis can induce antitumor activity in the cutaneous immune system through expression of melanoma tumour antigens that prime immune cells for destruction of local and metastatic melanoma lesions (Chen et al., 2023) A biosensing Staphylococcus epidermidis has been engineered to detect and destroy the skin pathogen MRSA through selective secretion of anti-MRSA antimicrobials released when in the presence of the target species, allowing regions of the skin to be cleared of this population without affecting other commensals and for local bioremediation of the cutaneous environment to take place post-infection (Guan et al., 2022) Non-cutaneous species of bacteria are also effective tools to target and reduce certain skin conditions. Topical application of Limosilactobacillus reuteri engineered to express human signalling molecules linked to wound repair was found to accelerate healing in human skin, with 76% of wounds healed after 32 days of treatment compared to just 59% of controls (Öhnstedt et al., 2023) Probiotics can be engineered to produce active ingredients beneficial for the skin. Topical application of such strains can release biotherapeutics like anti-inflammatory compounds or growth factors encouraging growth and repair of skin cells, combating signs of ageing by promoting wound repair and strengthening barrier function (Callewaert et al., 2021)   Industry impact & potential: Biotherapeutic companies are investing in genetically engineered bacteria for treatments, owing to their ease of application and precision. Azitra Inc uses microbial and protein engineering to devise novel therapeutics that treat skin conditions such as ichthyosis and Netherton syndrome, while Eligo Bioscience’s Eligobiotics® platform is capable of altering skin microbiome composition to selectively remove unwanted species linked to disease.   Our solution: As an industry leader in microbiome testing, Sequential is able to offer an end-to-end platform for in-vivo validation of your product and Gold Standard Certification of its efficacy. We have also partnered with 60+ high-end brands in the cosmeceutical space to help conceptualise and bring their products to the forefront of the skin microbiome market. References: Callewaert C, Knödlseder N, Karoglan A, Güell M, Paetzold B. Skin microbiome transplantation and manipulation: Current state of the art. Comput Struct Biotechnol J. 2021 Jan 4;19:624-631. doi: 10.1016/j.csbj.2021.01.001. PMID: 33510866; PMCID: PMC7806958. Chen, Y & Bousbaine, Djenet & Veinbachs, Alessandra & Atabakhsh, Katayoon & Dimas, Alex & Yu, Victor & Zhao, Aishan & Enright, Nora & Nagashima, Kazuki & Belkaid, Yasmine & Fischbach, Michael. (2023). Engineered skin bacteria induce antitumor T cell responses against melanoma. Science (New York, N.Y.). 380. 203-210. 10.1126/science.abp9563.  Guan C, Larson PJ, Fleming E, Tikhonov AP, Mootien S, Grossman TH, Golino C, Oh J. Engineering a "detect and destroy" skin probiotic to combat methicillin-resistant Staphylococcus aureus. PLoS One. 2022 Dec 15;17(12):e0276795. doi: 10.1371/journal.pone.0276795. PMID: 36520793; PMCID: PMC9754240. Knödlseder, N., Fábrega, MJ., Santos-Moreno, J. et al.  Delivery of a sebum modulator by an engineered skin microbe in mice. Nat Biotechnol  (2024). https://doi.org/10.1038/s41587-023-02072-4 Öhnstedt E, Vågesjö E, Fasth A, Lofton Tomenius H, Dahg P, Jönsson S, Tyagi N, Åström M, Myktybekova Z, Ringstad L, Jorvid M, Frank P, Hedén P, Roos S, Phillipson M. Engineered bacteria to accelerate wound healing: an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial. EClinicalMedicine. 2023 May 25;60:102014. doi: 10.1016/j.eclinm.2023.102014. PMID: 37251631; PMCID: PMC10220316.

Understanding preservatives Preservatives are added to cosmetic products to protect against the growth of pathogenic microorganisms and to extend the product's shelf life. However, as preservatives remain active on the skin upon application, there is a risk that they may alter the skin microbiome. A summary of what we know: The predominant genera of bacterial species on the skin’s microbiome are Cutibacterium, Staphylococcus  and Corynebacterium (Wang et al., 2018) In particular, C. acnes, S. epidermidis, and S. aureus act usually as commensal bacteria since they are harmless when the skin is healthy and are in a mutualistic relationship with the cutaneous system (Fournière et al., 2020; Pinto et al., 2021) Among these species, S.epidermidis is the most beneficial as it has been shown to protect against inflammation, infections, and cancer through interactions with keratinocytes, T cells, and other constituents of the skin microbiome (Stacy and Belkaid, 2019; Zhang et al., 2023) An in vitro study testing eleven different combinations of preservatives found that those containing hydroxyacetophenone, phenylpropanol, propanediol, caprylyl glycol, tocopherol, and tetrasodium glutamate diacetate were most suitable for restoring dysbiosis as they act moderately inhibiting C. acnes and strongly S. aureus without simultaneously inhibiting the growth of S. epidermidis (Pinto et al., 2021) An in vivo study on the leg skin microbiome revealed that different preservation systems had a minimal impact, suggesting that preservative systems do not have any detrimental impact on the structure or diversity of the skin microbiome for both rinse off and leave on products (Murphy et al., 2021) Industry impact & potential:   Symrise Cosmetic Ingredients multifunctional ingredients SymSave H and SymDiol 68 have shown to act in combination as a product protection system that maintains the natural flora of the skin More in vivo studies are needed to measure the long-term, accumulative effects of preservatives on the skin’s microbiome Our approach: We believe that cosmetic companies should re-evaluate their use of preservatives to help consumers maintain a healthy microbiome. Through formulation support and invivo testing we can advise on the most suitable preservative choice for your formulation and substantiate microbiome-related claims. References: Fournière M, Latire T, Souak D, Feuilloley MGJ, Bedoux G.  Staphylococcus epidermidis  and Cutibacterium acnes : Two Major Sentinels of Skin Microbiota and the Influence of Cosmetics. Microorganisms . 2020; 8(11):1752. https://doi.org/10.3390/microorganisms8111752 Murphy B, Hoptroff M, Arnold D, Eccles R, Campbell-Lee S. In-vivo impact of common cosmetic preservative systems in full formulation on the skin microbiome. PLoS One. 2021 Jul 7;16(7):e0254172. doi: 10.1371/journal.pone.0254172. PMID: 34234383; PMCID: PMC8263265. Pinto, D., Ciardiello, T., Franzoni, M. et al.  Effect of commonly used cosmetic preservatives on skin resident microflora dynamics. Sci Rep  11, 8695 (2021). https://doi.org/10.1038/s41598-021-88072-3 Stacy A, Belkaid Y. Microbial guardians of skin health. Science. 2019 Jan 18;363(6424):227-228. doi: 10.1126/science.aat4326. PMID: 30655428. Wang, Wen-Ming; Jin, Hong-Zhong. Skin Microbiome: An Actor in the Pathogenesis of Psoriasis. Chinese Medical Journal 131(1):p 95-98, January 05, 2018. | DOI: 10.4103/0366-6999.221269 Zhang W, Wang X, Zhao L, Gu Y, Chen Y, Liu N, An L, Lu Y, Cui S. Effect of leave-on cosmetic antimicrobial preservatives on healthy skin resident Staphylococcus epidermidis. J Cosmet Dermatol. 2023 Jul;22(7):2115-2121. doi: 10.1111/jocd.15690. Epub 2023 Mar 9. PMID: 36895166.

The scalp is home to millions of microbes that protect the skin from infection and promote functions like hair health and growth. Various cultures have used oil as a way to treat and bolster the look and feel of hair. Recent research suggests a beneficial effect of these practices on the microbes of the scalp, indicating a possible way to harness these materials to treat scalp health and associated conditions. What we know: The scalp is mostly colonised by species of Malassezia, Cutibacterium & Staphylococcus that inhabit the lipid-rich hair follicles of the scalp & work to regulate the hair cycle & immune system, and protect the skin from pathogens (Polak-Witka et al., 2019). After colonisation, they establish crosstalk with cells of the immune system, allowing them to influence cutaneous immune system behaviour, including maintenance of innate immunity, controlling inflammation & promoting tissue repair (Polak-Witka et al., 2019).  They also promote upregulation of metabolic pathways involved in nutrient synthesis & DNA maintenance required for scalp health & hairgrowth (Saxena et al., 2018). Vegetable hair oils (e.g., argan, coconut) are believed to confer benefits e.g. moisture, UV protection, reducing protein loss & delay hair greying via bioactive ingredients like B vitamins, proteins, and glycerides (Mysore & Arghya, 2022; Leite et al., 2018). Some research suggests application of coconut oil increases abundance of Cutibacterium acnes and Malassezia globosa in dandruff microbiomes to match healthy levels & reduce itching (Saxena et al., 2018). It also enriches biotin metabolism pathways and reduces fungal pathogenesis (a possible effect of its antimicrobial lauric acid content), showing ability to boost scalp health by modulating its respective microbiota and treat dysbiotic conditions like dandruff (Saxena et al., 2018). Industry impact & potential: As consumer interest in natural herbal cosmetic ingredients rises, more producers invest in such formulations for topical head use. Rosemary oil in recent years has become a huge trend in the hair care industry. A study (Panahi et al., 2015) compared the use of rosemary oil and minoxidil 2%, found evidence that rosemary oil was effective in treating androgenetic alopecia and that it had a lower frequency of scalp itching as a side effect compared to minoxidil 2%. Our solution: Backed by our Scientific Advisor Dr Tom Dawson who is an expert in hair health and the scalp microbiome, Sequential offers an end-to-end invivo scalp microbiome testing platform, giving product manufacturers opportunity to study the effects of their hair oils on microbiome and physical scalp skin parameters using our Gold Standard approach and personalised clinical assessment services. We also offer formulation support to support you and your brands needs when targeting products for certain treatments be it oily scalps, or hair loss. References:  Leite MGA, Maia Campos PMBG. Photoprotective Effects of a Multifunctional Hair Care Formulation Containing Botanical Extracts, Vitamins, and UV Filters. Photochem Photobiol. 2018 Sep;94(5):1010-1016. doi: 10.1111/php.12932. Epub 2018 May 25. PMID: 29729015. Mysore V, Arghya A. Hair Oils: Indigenous Knowledge Revisited. Int J Trichology. 2022 May-Jun;14(3):84-90. doi: 10.4103/ijt.ijt_189_20. Epub 2022 May 24. PMID: 35755964; PMCID: PMC9231528. Panahi Y, Taghizadeh M, Marzony ET, Sahebkar A. Rosemary oil vs minoxidil 2% for the treatment of androgenetic alopecia: a randomized comparative trial. Skinmed. 2015 Jan-Feb;13(1):15-21. PMID: 25842469. Polak-Witka K, Rudnicka L, Blume-Peytavi U, Vogt A. The role of the microbiome in scalp hair follicle biology and disease. Exp Dermatol. 2020 Mar;29(3):286-294. doi: 10.1111/exd.13935. Epub 2019 May 15. PMID: 30974503. Saxena R, Mittal P, Clavaud C, Dhakan DB, Hegde P, Veeranagaiah MM, Saha S, Souverain L, Roy N, Breton L, Misra N, Sharma VK. Comparison of Healthy and Dandruff Scalp Microbiome Reveals the Role of Commensals in Scalp Health. Front Cell Infect Microbiol. 2018 Oct 4;8:346. doi: 10.3389/fcimb.2018.00346. PMID: 30338244; PMCID: PMC6180232.

As the second most prevalent group of microbes found on the skin, fungi play an important role in regulating several processes related to skin immunity and disease. Although the skin mycobiome remains understudied, studies have begun to unmask the true extent of their involvement in skin function and health. Outline of research: Fungal colonisation plays an important role in developing and diversifying the early skin microbiome, mode of delivery also has an effect with vaginally born infants possessing more Malassezia and Candida albicans than Caesarean-born infants (Vijaya Chandra et al., 2021; Ward et al., 2018) This composition changes as an individual ages, with sex hormones like oestradiol and testosterone released during puberty causing an increase in the proportion of lipophilic taxa such as Malassezia and decreasing overall diversity (Nguyen & Kalan, 2022) The healthy skin mycobiome is most commonly composed of Malassezia spp. that colonise oily regions of the face like the sebaceous glands and can comprise up to 80% of the total fungal mycobiome (Gao et al., 2010) Malassezia spp. have been found to play possible roles in training the immune system and disrupting Staphylococcus aureus biofilm formation via enzyme secretion to prevent infection (Vijaya Chandra et al., 2021; Li et al., 2018) Mycobiome dysbiosis (i.e., changes in the proportion of certain fungal populations of the skin) has been linked to dermatological conditions such as pityriasis versicolor, pityrosporum folliculitis (fungal acne), and seborrheic dermatitis (Vijaya Chandra et al., 2021) Certain groups of fungi and bacteria can also work together to impair tissue repair during wound healing by forming polymicrobial biofilms that mediate inflammation and affect the quality of the host immune response (Cheong et al., 2021) Industry impact and potential: Many brands that seek to be mycobiome friendly and sensitive to fungal skincare conditions have started implementing ingredients such as: pyrithione zinc, azelaic acid, ketoconazole and sulphur.  Head & Shoulders is one of the most notable brands to have antifungal and Malassezia effects, containing active ingredients such as Salicylic Acid, Ketoconazole, and Selenium Sulphide that help to fight and control associated conditions such as seborrheic dermatitis. Our solution: Sequential offers bespoke services to develop and test the effects of your formulation on the skin, across both the face and scalp to support a healthy skin mycobiome and help prevent dysbiosis. Our Gold Standard Certification ensures your products are mycobiome-friendly and safe for use by customers suffering from dysbiotic conditions such as seborrheic dermatitis or pityrosporum folliculitis. References: Cheong, J.Z.A., Johnson, C.J., Wan, H. et al.  Priority effects dictate community structure and alter virulence of fungal-bacterial biofilms. ISME J  15, 2012–2027 (2021). https://doi.org/10.1038/s41396-021-00901-5 Gao ZPerez-Perez GIChen Y, Blaser MJ 2010.Quantitation of Major Human Cutaneous Bacterial and Fungal Populations. J Clin Microbiol48:. https://doi.org/10.1128/jcm.00597-10 Li H, Goh BN, Teh WK, Jiang Z, Goh JPZ, Goh A, Wu G, Hoon SS, Raida M, Camattari A, Yang L, O'Donoghue AJ, Dawson TL Jr. Skin Commensal Malassezia globosa Secreted Protease Attenuates Staphylococcus aureus Biofilm Formation. J Invest Dermatol. 2018 May;138(5):1137-1145. doi: 10.1016/j.jid.2017.11.034. Epub 2017 Dec 12. PMID: 29246799. Nguyen UT, Kalan LR. Forgotten fungi: the importance of the skin mycobiome. Curr Opin Microbiol. 2022 Dec;70:102235. doi: 10.1016/j.mib.2022.102235. Epub 2022 Nov 11. PMID: 36372041; PMCID: PMC10044452. Vijaya Chandra SH, Srinivas R, Dawson TL Jr, Common JE. Cutaneous Malassezia:  Commensal, Pathogen, or Protector? Front Cell Infect Microbiol. 2021 Jan 26;10:614446. doi: 10.3389/fcimb.2020.614446. PMID: 33575223; PMCID: PMC7870721. Ward TL, Dominguez-Bello MG, Heisel T, Al-Ghalith G, Knights D, Gale CA.2018.Development of the Human Mycobiome over the First Month of Life and across Body Sites. mSystems3:10.1128/msystems.00140-17. https://doi.org/10.1128/msystems.00140-17

The oralome describes the interactions between the diverse range of species of bacteria, fungi, viruses, archaea and protozoa occupying numerous habitats of the oral cavity. Being influenced by factors like food, hygiene, and environment, disruption of this delicate balance is able to cause downstream effects that are detrimental to both oral and global bodily health, creating a need for effective therapies that restore normal function.   What we know: Of the ~1000 microbial species comprising the oralome, bacteria are the most abundant. The human oralome consists of 774 bacterial species, mostly belonging to Gemella, Granulicatella Streptococcus, and Veillonella, while non-bacterial species include bacteriophages, fungi, and methane-producing archaea (Radaic & Kapila, 2021; Aas et al., 2005). Healthy individuals possess more probiotic commensals that secrete antimicrobials to inhibit disease progression and train the immune system to defend against pathogens (Belda-Ferre et al., 2012). Unhealthy behaviours (poor oral hygiene and diet, smoking) promotes growth of dysbiotic bacterial biofilms 1000x more resistant to antibiotics than usual that adhere to the oral cavity and cause tooth decay and gum disease (Sudhakara et al., 2018; Kouidhi et al., 2015; Dewhirst et al., 2010). This dysbiosis may spread from the mouth to impact other regions of the body, usually via bacteremia or the oral-gut axis, contributing to non-oral diseases like Atherosclerosis, Alzheimer’s disease, and IBD (Radaic & Kapila, 2021; Park et al., 2021). Plant medicinal compounds, like those from S. persica and C. sinensis, can inhibit biofilm growth by preventing bacterial communication and attachment (Al-Sohaibani & Murugan, 2012; Xu et al., 2012). Other possible anti-biofilm solutions include prebiotics to limit pathobiont growth, probiotics to improve mucosal immunity against oral disease, and chemicals to disrupt biofilm formation (Radaic & Kapila, 2021).   Industry impact & potential: Many brands are now considering the power of probiotics as a way to treat and combat dental disease.   Gallinée Microbiome Skincare’s Mouth & Microbiome supplement promotes oralome health by maintaining the environments good bacteria inhabit. It contains probiotics and vitamins D3 and B8 that maintain healthy teeth and mucous membranes.   Our Solution: Sequential is the leading expert in microbiome testing, with a Gold Standard in-vivo end-to-end platform, allowing your brand to reliably test the efficacy of your product on promoting and maintaining a healthy oral microbiome. This approach ensures greater accuracy and representativeness when considering formulation efficacy and optimality, and also includes sequencing services to give you in-depth analytical comparison on how your formulation can influence the oralome. References: Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol. 2005 Nov;43(11):5721-32. doi: 10.1128/JCM.43.11.5721-5732.2005. PMID: 16272510; PMCID: PMC1287824. Al-Sohaibani S, Murugan K. Anti-biofilm activity of Salvadora persica on cariogenic isolates of Streptococcus mutans: in vitro and molecular docking studies. Biofouling. 2012;28(1):29-38. doi: 10.1080/08927014.2011.647308. PMID: 22235758. Belda-Ferre P, Alcaraz LD, Cabrera-Rubio R, Romero H, Simón-Soro A, Pignatelli M, Mira A. The oral metagenome in health and disease. ISME J. 2012 Jan;6(1):46-56. doi: 10.1038/ismej.2011.85. Epub 2011 Jun 30. PMID: 21716308; PMCID: PMC3246241. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG. The human oral microbiome. J Bacteriol. 2010 Oct;192(19):5002-17. doi: 10.1128/JB.00542-10. Epub 2010 Jul 23. PMID: 20656903; PMCID: PMC2944498. Kouidhi B, Al Qurashi YM, Chaieb K. Drug resistance of bacterial dental biofilm and the potential use of natural compounds as alternative for prevention and treatment. Microb Pathog. 2015 Mar;80:39-49. doi: 10.1016/j.micpath.2015.02.007. Epub 2015 Feb 21. PMID: 25708507. Park S-Y, Hwang B-O, Lim M, Ok S-H, Lee S-K, Chun K-S, Park K-K, Hu Y, Chung W-Y, Song N-Y. Oral–Gut Microbiome Axis in Gastrointestinal Disease and Cancer. Cancers . 2021; 13(9):2124. https://doi.org/10.3390/cancers13092124 Radaic A, Kapila YL. The oralome and its dysbiosis: New insights into oral microbiome-host interactions. Comput Struct Biotechnol J. 2021 Feb 27;19:1335-1360. doi: 10.1016/j.csbj.2021.02.010. PMID: 33777334; PMCID: PMC7960681. Sudhakara P, Gupta A, Bhardwaj A, Wilson A. Oral Dysbiotic Communities and Their Implications in Systemic Diseases. Dent J (Basel). 2018 Apr 16;6(2):10. doi: 10.3390/dj6020010. PMID: 29659479; PMCID: PMC6023521. Xu X, Zhang W, Huang C, Li Y, Yu H, Wang Y, Duan J, Ling Y. A novel chemometric method for the prediction of human oral bioavailability. Int J Mol Sci. 2012;13(6):6964-6982. doi: 10.3390/ijms13066964. Epub 2012 Jun 7. PMID: 22837674; PMCID: PMC3397506.

The impact of environmental factors on skin health is a compelling area of study, and understanding these regional influences can offer valuable insights for personalised skin care practices. Current research: A recent study dives deep into the skin's microbial world, unravelling regional variations in facial microbiome and metabolites (Tao, Rong, et al 2023). The study examines variations in bacterial and fungal communities, as well as skin metabolites, among 71 individuals from diverse climates in Northern, Southern, Northwestern China. The study found that regions with distinct climates such as temperate monsoon (North), subtropical monsoon (South), and temperate continental monsoon (Northwest), show significant differences in bacterial, fungal communities, and skin metabolites.  Notably, the Northwest exhibits a unique skin profile with higher ceramides, lower eicosanoids, and reduced total lipids, suggesting a potential boost to the skin barrier. This unique profile correlated with a diminished presence of Malassezia, suggesting a complex interplay between lipids and microbial composition in influencing skin health. The North, characterised by a warm climate, displayed higher bacterial diversity and elevated levels of Malassezia. Staphylococcus, and Cutibacterium were also prevalent in the North, particularly with an increased abundance of Staphylococcus epidermidis. Fungal diversity peaked in the Northwest, marked by elevated Cladosporium, Candida, and Aspergillus, and reduced M. globosa. Increased bacterial diversity in the warm North and elevated fungal diversity in the Northwest highlight climate-associated shifts in skin microorganisms. Industry Impact & Potential: Understanding climate-associated shifts in skin microorganisms offers insights crucial for skincare industries. The study above underscores the nuanced relationship between environmental factors and skin health, shedding light on personalised skin care practices. Companies can leverage this knowledge to develop climate-specific skincare solutions tailored to individual needs. Further research could explore the underlying mechanisms of these variations and investigate how the facial microbiome and metabolite compositions change dynamically over time. Conducting more comprehensive studies that consider physiological parameters and diverse demographics would provide valuable insights. Our Solution: Sequential stands at the forefront of skincare innovation, ready to help you incorporate cutting-edge research findings into your product. By aligning with the latest insights on facial microbiome and skin health, we can help brands come up with personalised skincare solutions that adapt to diverse climates, providing optimal care for your unique skin. References: Tao R, Li T, Wang Y, Wang R, Li R, Bianchi P, Duplan H, Zhang Y, Li H, Wang R. The facial microbiome and metabolome across different geographic regions. Microbiol Spectr. 2024 Jan 11;12(1):e0324823. doi: 10.1128/spectrum.03248-23. Epub 2023 Dec 8. PMID: 38063390; PMCID: PMC10783011.

Skincare products formulated with prebiotic ingredients feed and support the skin microbiome. Through varying mechanisms, research shows that honing in on this element of microbiome-conscious skincare may yield optimal skin health. What We Know: Prebiotic skincare has demonstrated effectiveness in increasing skin hydration, increasing commensal microbiota (e.g., Staphylococcus equorum, Streptococcus mitis and Halomonas desiderata) as well as decreasing levels of opportunistic pathogens (e.g., Pseudomonas stutzeri and Sphingomonas anadarae) (Li et al., 2023). Researchers examined the skin microbiome and metabolome and concluded that by altering the skin microbiome composition and favouring bacteria capable of producing hydrating metabolites, prebiotic-containing skincare enhanced skin health (Li et al., 2023). In this study, the prebiotic ingredients were administered in conjunction with pro- and postbiotics in what researchers term ‘a triple-biotic complex,’ specifically containing inulin (prebiotic), a butyloctanol (a "smart biotic") and lactic acid and pyruvic acid (postbiotics) in the form of Sanex BiomeProtect shower gel and body lotion (Li et al., 2023). Additional research showed that the prebiotic-containing skincare products were able to manage atopic dermatitis and xerosis symptoms by normalising skin microbiota and preserving skin barrier integrity (Dumbuya et al., 2024). The hypothesised mechanism of action was that these prebiotic-enriched products support an acidic pH balance, which favours commensal species and disrupts pathogenic species (Dumbuya et al., 2024). Participants incorporated a prebiotic cleanser (the La Roche-Posay Lipikar AP+ Gentle Foaming Cleansing Oil), which included niacinamide, shea butter, glycerin and a prebiotic moisturiser (the La Roche-Posay Lipikar AP+M Moisturizing Cream), which contains ceramide, shea butter, niacinamide, glycerin, Microresyl (trademark from La Roche-Posay) and Aqua posae filiformis (Dumbuya et al., 2024). Industry Impact and Potential: Investigation into prebiotic-containing products is an exciting avenue in the microbiome-conscious skincare realm. Researching and testing the effects of various pre-, pro- and postbiotics, and the combinations thereof, provide potential targets for innovative topical treatments aimed at improving skin hydration and overall skin health (Li et al., 2023). Our Solution: Sequential provides a comprehensive end-to-end Microbiome Product Testing Solution coupled with expert guidance in product development and formulation. Drawing on our extensive expertise, we collaborate with businesses to pioneer innovative strategies for creating topical treatments that, for example, may harness the power of prebiotics. Our tailored approach aims to address a spectrum of skin diseases and inflammatory conditions, offering cutting-edge solutions, research and technology. References: Dumbuya H, Podimatis K, Kerob D, Draelos ZD. INDIVIDUAL ARTICLE: Efficacy of a Prebiotic Skincare Regimen on Improving Mild Atopic Dermatitis and Severe Xerosis in Diverse Ethnically Patients. J Drugs Dermatol. 2024 Mar 1;23(3):SF395747s12-SF395747s22. doi: 10.36849/jdd.SF395747. PMID: 38443135. Li M, Mao J, Diaz I, Kopylova E, Melnik AV, Aksenov AA, Tipton CD, Soliman N, Morgan AM, Boyd T. Multi-omic approach to decipher the impact of skincare products with pre/postbiotics on skin microbiome and metabolome. Front Med (Lausanne). 2023 Jul 18;10:1165980. doi: 10.3389/fmed.2023.1165980. PMID: 37534320; PMCID: PMC10392128.

The hydrobiome is defined as the natural microbial community present in water. Thermal spring water contains macro and microelements, as well as trace elements that have proven their effectiveness in treating several skin conditions such as atopicdermatitis and acne. Recent research has linked the hydrobiome of these waters with a balance of the skin’s microbiome. A summary of what we know: Microbial diversity has been investigated in several waters and is shown to be impacted by factors such as environment and mineral composition (Mourelle, Gómez and Legido, 2023) Studies have shown the dominant bacterial phyla in several hots springs to be Actinobacteria, Firmicutes and Chloroflexi (Mourelle, Gómez and Legido, 2023) A recent study compared the effects of Lakitelek thermal water and tap water on the skin’s microbiome in healthy volunteers, showing that the number of inflammatory agent Pseudomonas decreased and the Deinococcus genus increased, which is known to play an important role in inhibiting Staphylococcus aureus infection (Tamás et al., 2023) Additionally, hypersaline environments such as water from the Dead Sea have been recognised as treatment for various skin diseases (Dai et al., 2023) Industry impact & potential: Several companies have conducted research on hydrobiome-derived ingredients such as extracts and lysates. There is huge potential for these ingredients to be used in cosmetics as bioactive ingredients, however, there is a lack of research on how the hydrobiome of thermal waters can play a role in having therapeutic effects on the skin. More in vivo studies are needed to identify the interactions between the hydrobiome and the skin microbiome. Our solution: If you are interested in formulating with thermal water or hydrobiome-derived ingredients, we offer formulation support and in vivo  microbiome testing to demonstrate the effects on the skin microbiome and substantiate microbiome-related claims. References: Dai D, Ma X, Yan X, Bao X. The Biological Role of Dead Sea Water in Skin Health: A Review. Cosmetics . 2023; 10(1):21. https://doi.org/10.3390/cosmetics10010021 Mourelle, María Lourdes & Gómez, Carmen & Legido Soto, José Luis. (2023). Hydrobiome of Thermal Waters: Potential Use in Dermocosmetics. Cosmetics. 10. 94. 10.3390/cosmetics10040094.  Tamás B, Gabriella K, Kristóf Á, Anett I, János Pál K, Bálint T, Péter L, Márton P, Katalin N. The Effects of Lakitelek Thermal Water and Tap Water on Skin Microbiome, a Randomized Control Pilot Study. Life (Basel). 2023 Mar 9;13(3):746. doi: 10.3390/life13030746. PMID: 36983902; PMCID: PMC10051609.