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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.

Mycocosmetics are a recently emerging trend in cosmeceuticals looking to utilise the power of mushroom-based ingredients when developing products for skin. Enriched in bioactives and nutrients, these bodies have potential to protect and strengthen skin in several ways from sensitivity to ageing, and can be used in multiple formulations to help achieve these goals efficiently and naturally. What we know: Mushrooms contain several key ingredients like proteins, vitamins, b-glucans, riboflavin, and niacin that are able to promote healthy processes in the skin such as wound healing, moisturising, nourishing, and protecting against sun damage (Wu et al., 2016). Enriched in bioactives e.g. polysaccharides and phenolics, mushrooms also have the potential to provide immunomodulatory, antioxidant, and anti-inflammatory effects that may provide additional benefit for those with damaged or sensitive skin (Wu et al., 2016). Some of the most popular species used in topical product formulations include shiitake, oyster, portobello, and cauliflower mushrooms, with this popularity due to an abundance of beneficial mycochemicals for the skin like antimicrobial alkaloids, anti-inflammatory phenols, and antioxidant saponins (Wu et al., 2016). Mushroom extracts can be used as ingredients in cosmetic formulations to treat a variety of skin conditions, many possessing anti-tyrosine, anti-hyaluronidase, anti-elastase, anti-collagenase activity to limit issues like hyperpigmentation, increase skin suppleness, and maintain skin elasticity and structure (Taofiq et al., 2016). Individual bioactives found in mushrooms that drive these effects include p-Coumaric acid, which is able to reduce hyperpigmentation up to 77% in human skin, ascorbyl coumarates that promotes collagen release by up to 191%, and ergothioneine, which suppresses MMP-1 (collagen degraders) activity by 52% (Taofiq et al., 2016). Industry impact & potential: With a recent push in the cosmetic industry to use natural, clean ingredients, brands are looking to supplement their formulations with mushrooms. Origins has launched their Dr Andrew Weil line of Reishi mushroom-extract infused creams and serums to provide instant hydration, barrier boosting and defence against environmental stressors. Herbar’s The Face Nectar contains several mushrooms like Turkey Tail, Matsutake, Tremella, and Reishi to promote hydration, vitality, firming, and skin evenness. Our solution: Our end-to-end invivo testing platform offers clients the opportunity to test the efficacy of their mycocosmetic formulations in addressing their primary target areas of concern for the skin. We also offer personalised formulation guidance to help optimise and refine your product and Gold Standard Certification for skin care, as well as mushroom-infused products addressing hair care, oral, and vaginal concerns to validate your brand. References: Taofiq O, Heleno SA, Calhelha RC, Alves MJ, Barros L, Barreiro MF, González-Paramás AM, Ferreira IC. Development of Mushroom-Based Cosmeceutical Formulations with Anti-Inflammatory, Anti-Tyrosinase, Antioxidant, and Antibacterial Properties. Molecules. 2016 Oct 14;21(10):1372. doi: 10.3390/molecules21101372. PMID: 27754433; PMCID: PMC6274557. Wu Y, Choi M-H, Li J, Yang H, Shin H-J. Mushroom Cosmetics: The Present and Future. Cosmetics . 2016; 3(3):22. https://doi.org/10.3390/cosmetics3030022

The scalp microbiome plays an important role in regulating hair growth, dandruff and sebum secretion, as well as preventing scalp conditions. Research has shown that amongst the multiple different approaches investigated to improve and maintain scalp health, postbiotic products may provide an innovative and unexplored answer.  What We Know: Malassezia, Cutibacterium  and Staphylococcus  are common on healthy and diseased scalps, with species like M. restricta, M. globosa, C. acnes  and S. epidermidis. Malassezia  causes dandruff and hair loss while Cutibacterium  and Staphylococcus  are linked to scalp inflammation. C. acnes  and S. epidermidis  inhibit each other (Tsai et al., 2023) . Postbiotics are non-viable probiotics consisting of its cell components and metabolites with great immunomodulation ability (Almeida, Antiga & Lulli, 2023) . Industry Impact and Potential: Research investigating the effect of heat-killed probiotics consisting of Lacticaseibacillus paracasei  GMNL-653 on scalp health was performed using a 5-month clinical trial wherein participants used a shampoo containing heat-killed GMNL-653 (HKG). The results included reduced dandruff and oil secretion, as well as increased hair growth (Tsai et al., 2023) . Further results demonstrated that the HKG co-aggregated with scalp fungus Malassezia furfur  in vitro and its lipoteichoic acid inhibited M. furfur biofilm formation on skin cells. Furthermore, HKG treatment up-regulated growth factor mRNA linked to hair follicle development in human cell lines (Tsai et al., 2023) . HKG’s impact on the scalp microbiome included an increase in Malassezia globosa  abundance and a decrease in M. restricta  and C. acnes levels. Additionally, M. globosa  showed a positive correlation with Lacticaseibacillus paracasei  and a negative correlation with C. acnes . Levels of C. acnes  and S. epidermidis  were positively associated with sebum secretion and dandruff, respectively ( Tsai et al., 2023) . Additional research on Sensitive Scalp Syndrome (SSS) investigated the effects of a postbiotic in the form of a topical Saccharomyces  and Lactobacillus  ferment complex (SLFC) on the scalp microbiome. Researchers established that the product was effective in alleviating SSS symptoms after 28 days of twice-daily application (Wang et al., 2023)   SLFC caused an increase in Staphylococcus, Lawsonella  and Fusarium  and a decrease of Cutibacterium  and Malassezia   (Wang et al., 2023) .  Our Solution: With a database of 20,000 microbiome samples and 4,000 ingredients, plus a global network of 10,000 testing participants, Sequential provides customised solutions for microbiome studies and product formulation. Our commitment to developing microbiome-safe products ensures the preservation of biome integrity, making us an ideal partner for your scalp and hair care product development needs, including the exploration of postbiotic scalp care solutions. References: Almeida, C.V.D., Antiga, E. & Lulli, M. (2023) Oral and Topical Probiotics and Postbiotics in Skincare and Dermatological Therapy: A Concise Review. Microorganisms . 11 (6). doi:10.3390/microorganisms11061420. Tsai, W.-H., Fang, Y.-T., Huang, T.-Y., Chiang, Y.-J., Lin, C.-G. & Chang, W.-W. (2023) Heat-killed Lacticaseibacillus paracasei GMNL-653 ameliorates human scalp health by regulating scalp microbiome. BMC microbiology . 23 (1), 121. doi:10.1186/s12866-023-02870-5. Wang, Y., Li, J., Wu, J., Gu, S., Hu, H., Cai, R., Wang, M. & Zou, Y. (2023) Effects of a Postbiotic Saccharomyces and Lactobacillus Ferment Complex on the Scalp Microbiome of Chinese Women with Sensitive Scalp Syndrome. Clinical, Cosmetic and Investigational Dermatology . 16, 2623–2635. doi:10.2147/CCID.S415787.

Fluoride has been used for the purpose of dental health for years. It is known to prevent tooth decay and strengthen the enamel. It’s also commonly used in dental products such as toothpaste and mouthwash. The oral cavity is home to a complex and diverse microbiome that plays a crucial role in maintaining oral health. Recent research has begun to explore how fluoride, beyond its well-known benefits, influences the composition and function of this oral microbiome.  What we know: Fluoride inhibits demineralisation, promotes tooth remineralisation, and inhibits the growth of plaque bacteria (Nassar et al ., 2023). Fluoride has been found to inhibit the growth of acid-producing bacteria like Streptococcus mutans , which are primarily responsible for tooth decay (Son et al ., 2020). Fluoride also inhibits the growth of a variety of oral microorganisms, such as Streptococcus sialis, Lactobacillus, Porphyromonas gingivalis, Streptococcus sanguis, and Candida albicans  (Yang et al ., 2023). Fluoride restricts various enzymes involved in bacterial metabolism, particularly those in glycolysis. By preventing enzymes like enolase, fluoride disrupts the energy production pathways of bacteria, making it difficult for them to thrive in the oral environment (Moran et al ., 2023). Fluoride selectively targets cariogenic bacteria without completely eradicating the entire bacterial community. This selective action helps maintain a balance within the oral microbiome, reducing the risk of dental caries while preserving beneficial bacteria (Han., 2021). Fluoride can influence the formation and composition of dental biofilms, by disrupting the biofilm architecture, making it less likely for the growth of pathogenic bacteria (Han., 2021). Industry impact & potential: Although some studies have been carried out on the impact of fluoride on the oral microbiome, there is a need for large population-based studies to assess the impact of fluorides on the oral microbiome in children and adults (Moran et al ., 2023). Fluoride exposure has a beneficial effect on the oral microbiome, however the long-term consequences of this require further study  (Moran et al ., 2023). The potential development of fluoride-resistant bacteria highlights the need for alternative or complementary treatments. Research into probiotics or other antimicrobial agents that work with fluoride could provide new avenues for maintaining oral health. Our solution: Through advanced in vivo testing and profiling, we aim to understand the oral microbiome and enhance oral health by targeting the root causes of dental caries while maintaining a balanced and healthy oral microbiome.  Reference: Han Y. Effects of brief sodium fluoride treatments on the growth of early and mature  cariogenic biofilms. Sci Rep. 2021 Sep 14;11(1):18290. doi: 10.1038/s41598-021-97905-0. PMID: 34521969; PMCID: PMC8440647. Moran GP, Zgaga L, Daly B, Harding M, Montgomery T. Does fluoride exposure impact on the  human microbiome? Toxicol Lett. 2023 Apr 15;379:11-19. doi: 10.1016/j.toxlet.2023.03.001. Epub 2023 Mar 4. PMID: 36871794. Nassar Y, Brizuela M. The Role of Fluoride on Caries Prevention. 2023 Mar 19. In:  StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 36508516. Son JL, Kim AJ, Oh S, Bae JM. Inhibitory effects on Streptococcus mutans of antibacterial  agents mixed with experimental fluoride varnish. Dent Mater J. 2020 Aug 2;39(4):690-695. doi: 10.4012/dmj.2020-016. Epub 2020 Jun 9. PMID: 32522914. Yang Z, Cai T, Li Y, Jiang D, Luo J, Zhou Z. Effects of topical fluoride application on oral  microbiota in young children with severe dental caries. Front Cell Infect Microbiol. 2023 Mar 7;13:1104343. doi: 10.3389/fcimb.2023.1104343. PMID: 36960045; PMCID: PMC10028198.