Search Results

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.

The oral microbiome evolves throughout different stages of life, particularly during pregnancy. Research has linked adverse pregnancy outcomes (like preterm birth, preeclampsia and low birth weight) to the oral microbiome, highlighting the urgent need to explore specialised oral microbiome care during this period. What We Know: The oral microbiomes of pregnant women have higher total viable microbial counts compared to non-pregnant women, particularly in the first trimester (Fujiwara et al., 2017) . Microbial diversity remains stable during pregnancy, but the composition of the oral microbiome shifts toward a pathogenic state. This change, likely mediated by progesterone and oestrogen, reverts back to a healthy microbiome during the postpartum period (Ye & Kapila, 2021) .   Research has shown that Neisseria , Porphyromonas  and Treponema  were more prevalent in pregnant women, while Streptococcus  and Veillonella  were seen to be less common, compared to non-pregnant women. However, other studies found that Fusobacteria  and Spirochaetes  were more abundant during pregnancy, whereas Haemophilus , Neisseria , Streptococcus  and Rothia  were less prevalent. This compositional shift during pregnancy may increase the risk of infection by harmful oral microbiota, potentially triggering disease (Ye & Kapila, 2021) .  Pregnancy gingivitis affects 30-100% of women worldwide. Studies have found that increased levels of Po. gingivalis, Tr. denticola, Pr. intermedia, Ta. forsythia, Campylobacter rectus, A. actinomycetemcomitans  and Fretibacterium  in the oral microbiome are linked to gingival inflammation during pregnancy. Conversely, higher levels of Rothia dentocariosa  in saliva are associated with reduced gingival inflammation during pregnancy (Ye & Kapila, 2021) .  Industry Impact and Potential: Maintaining a balanced oral microbiome is crucial for a healthy pregnancy, as disruptions in the microbiome can contribute to pregnancy complications (Saadaoui, Singh & Al Khodor, 2021) . Further research is needed to fully elucidate the role of the oral microbiome during pregnancy, specifically exploring its role in gingival inflammation and association to adverse pregnancy outcomes (Cobb et al., 2017) . By understanding how the microbiome evolves and influences pregnancy outcomes, we can pioneer preventive strategies that enhance maternal well-being and foetal development (Cobb et al., 2017) . Our Solution: Sequential is an industry leader in comprehensive microbiome product testing and formulation. Our expertise and customisable services empower businesses to innovate confidently in developing oral hygiene products that preserve microbiome integrity, ensuring their efficacy and compatibility for a healthier oral microbiome. We are the ideal partner to help your company explore the potential of oral care during pregnancy. References: Cobb, C.M., Kelly, P.J., Williams, K.B., Babbar, S., Angolkar, M. & Derman, R.J. (2017) The oral microbiome and adverse pregnancy outcomes. International Journal of Women’s Health. Fujiwara, N., Tsuruda, K., Iwamoto, Y., Kato, F., Odaki, T., Yamane, N., Hori, Y., Harashima, Y., Sakoda, A., Tagaya, A., Komatsuzawa, H., Sugai, M. & Noguchi, M. (2017) Significant increase of oral bacteria in the early pregnancy period in Japanese women. Journal of Investigative and Clinical Dentistry. 8 (1), e12189. doi:10.1111/jicd.12189. Saadaoui, M., Singh, P. & Al Khodor, S. (2021) Oral microbiome and pregnancy: A bidirectional relationship. Journal of Reproductive Immunology. 145, 103293. doi:10.1016/j.jri.2021.103293. Ye, C. & Kapila, Y. (2021) Oral microbiome shifts during pregnancy and adverse pregnancy outcomes: Hormonal and Immunologic changes at play. Periodontology 2000. 87 (1), 276–281. doi:10.1111/prd.12386.

A brief overview of the climate crisis: Evidence strongly suggests that anthropogenic climate change caused by greenhouse gas emissions will continue causing major disruptions to the earth’s environmental systems. Climate change and pollution are changing our environment and subsequently, external factors to which individuals are exposed. Studies indicate that the skin microbiome is affected by these factors, which may influence the development or severity of skin conditions such as acne, atopic dermatitis and skin cancer. A summary of what we know: Climate variables, specifically temperature, humidity, UV radiation and air pollution may have modulating effects on the skin microbiome that could influence skin health (Isler, Coates and Boos, 2022) Studies have reported that both UVA and UVB can cause hyperplasia of sebaceous glands and thickening of the stratum corneum, potentially altering the microbial landscape by promoting growth of lipophilic organisms such as C.acnes and Malassezia (Dréno et al., 2018; Isler, Coates and Boos, 2022) Studies have also found that a temperature increase of 1°C leads to an increase in the effective UV dose by 2%, increasing skin cancer risk via keratinocyte DNA damage, leading to possible loss of skin bacteria that release antioxidant products which serve to protect against carcinogenesis (Isler, Coates and Boos, 2022) Additionally, air pollution such as particulate matter, nitrogen dioxide, and sulfur dioxide have been associated with increased outpatient visits for post-adolescent acne in China (Li et al., 2022) Industry impact & potential: Further studies using in vivo testing will be necessary to evaluate the effects of climate change on the skin microbiome more precisely, and propose product solutions. An example of innovation in this space is a biomimetic active, Galactinol Advanced by Clariant, that activates the skin's defense mechanisms to improve its resilience towards environmental stress and quickly changing climate. Our approach: Understanding how the changing environment affects our skin microbiome will be key to the future treatment and prevention of skin conditions. At Sequential, we are able to partner with clinical and personal care product companies to offer leading-edge in vivo microbiome testing, certification and formulation support to assist the development of products that help to protect the skin from environmental stresses whilst maintaining the microbiome. References: Dréno B, Bettoli V, Araviiskaia E, Sanchez Viera M, Bouloc A. The influence of exposome on acne. J Eur Acad Dermatol Venereol. 2018 May;32(5):812-819. doi: 10.1111/jdv.14820. Epub 2018 Feb 15. PMID: 29377341; PMCID: PMC5947266. Isler, Madeleine & Coates, Sarah & Boos, Markus. (2022). Climate change, the cutaneous microbiome and skin disease: implications for a warming world. International Journal of Dermatology. 62. 10.1111/ijd.16297.  Li X, An SJ, Liu XL, Ji AL, Cao Y, Xiang Y, Ma XY, Hu Q, Yuan ZQ, Li YF, Lu YG, Cai TJ. The Association Between Short-Term Air Pollution Exposure and Post-Adolescent Acne: The Evidence from a Time Series Analysis in Xi'an, China. Clin Cosmet Investig Dermatol. 2021 Jun 25;14:723-731. doi: 10.2147/CCID.S320248. PMID: 34211290; PMCID: PMC8241005.

The skin microbiome, particularly the axillary (armpit) region, is covered by dense secretory glands, such as apocrine, eccrine, and sebaceous glands. These glands secrete various nutrients and moisten skin folds such as the armpit, which provides habitable growth conditions for odour-causing bacteria. A summary of what we know: Sweat is an odourless liquid mostly comprised of water, electrolytes, and proteins, and the formation of an unpleasant odour is a result of the metabolic activity of the microbiome habituated in the axillary region (Teerasumran et al., 2023) There are four primary types of bacterial species involved in malodour compound production, Cutibacterium, Micrococci, Staphylococcus, and Corynebacterium with the latter two being the most prominent (Teerasumran et al., 2023) The bacterial community in the armpit decomposes the odourless sweat into volatile odorous byproducts, such as volatile fatty acids (VFAs), 3-hydroxy hexanoic acid (3M3H), and 3-hydroxy-3-methylhexanoic acid (HMHA) (Kim et al., 2021; Fredrich et al., 2013) The mechanism of action of deodorants relies on the use of antimicrobial agents to inhibit the growth of body odour-­forming microbial species, however complete suppression of the axillary microbiome can lead to dysbiosis (Teerasumran et al., 2023) Recent research has shown the potential prebiotic effect of 2- butyloctanol which inhibited odour-causing Corynebacterium  whilst maintaining skin-friendly Staphylococcus  in the axillary microbiome (Li et al., 2021) Industry impact & potential: Brands and ingredient manufacturers have started to show care for the underarm microbiome by introducing clean, sustainable and low preservative formulas Symrise Cosmetic Ingredients biodegradable deodorant active SymDeo® B125, effectively prevents malodours and claims ‘microbiome-friendly’ with ex vivo tests showing selective activity on odour-causing Gram-positive bacteria Pioneering microbiome brand Aurelia London (part of H&H Group) Probiotic Skincare’s Botanical Cream Deodorant is a multi-award winning formula that claims to ‘eliminate odour-causing bacteria’ Our Solution: We have helped some of the world's leading companies to test their microbiome-based deodorant formulations. In our clinical studies, we’ve observed some significant shifts in specific microbial taxa, such as Corynebacterium, and corresponding reports of improvements in malodour. Our work suggests that we may be entering the next generation for effective deodorants - significantly disrupting our traditional take on smelling fresh. As studies are primarily based on invitro studies, it will be critical to do further clinical studies in vivo  to demonstrate there is a translation to improved microbiome health, mirroring a reduction in malodour. References: Fredrich E, Barzantny H, Brune I, Tauch A. Daily battle against body odor: towards the activity of the axillary microbiota. Trends Microbiol. 2013 Jun;21(6):305-12. doi: 10.1016/j.tim.2013.03.002. Epub 2013 Apr 6. PMID: 23566668. Kim MJ, Tagele SB, Jo H, Kim MC, Jung Y, Park YJ, So JH, Kim HJ, Kim HJ, Lee DG,  Kang S, Shin JH. Effect of a bioconverted product of Lotus corniculatus seed on the axillary microbiome and body odor. Sci Rep. 2021 May 12;11(1):10138. doi: 10.1038/s41598-021-89606-5. PMID: 33980951; PMCID: PMC8115508. Li M, Truong K, Pillai S, Boyd T, Fan A. The potential prebiotic effect of 2-Butyloctanol on the human axillary microbiome. Int J Cosmet Sci. 2021 Dec;43(6):627-635. doi: 10.1111/ics.12738. Epub 2021 Oct 6. PMID: 34448215. Teerasumran P, Velliou E, Bai S, Cai Q. Deodorants and antiperspirants: New trends in  their active agents and testing methods. Int J Cosmet Sci. 2023 Aug;45(4):426-443. doi: 10.1111/ics.12852. Epub 2023 Mar 21. PMID: 36896776; PMCID: PMC10946881.

Background on Malassezia The skin surface micro-environment is colonised by a wide range of microorganisms, including bacteria, archaea, viruses, and fungi. Collectively this is referred to as the skin microbial community or microbiome. Malassezia  was discovered in the 19th century by Malassez and Sabaouraud. Malassezia  is the major component of the fungal skin microbiota, is present on all humans (and warm-blooded animals), and is most abundant on sebaceous (oily) body sites. It is a lipid dependent microbe, which is quite unusual. As shown below, in different areas of the body, even if it is oily, moist or dry, Malassezia  is the only resident fungi found on all skin. The only skin area with a higher diversity is the toes and the feet, where there is a rich diversity of skin fungi. For example, there are a variety of different fungi related to athlete's foot and nail fungus. Of course, our feet are our connection to the outside environment so this makes sense, as evolutionarily speaking feet would have a higher diversity of fungi because they (without wearing shoes) are exposed to more microbes than other areas of the skin. https://www.science.org/doi/10.1126/science.1260144 Recent Studies Professor Thomas Dawson is a major player in skin microbiota and has spent his career understanding this specific microbe called Malassezia . His work has been aimed at uncovering whether Malassezia  is commensal, pathogenic, or protective (mutualistic), and this work is what we will focus on here. A literature review paper ‘Cutaneous Malassezia : Commensal, Pathogenic, or Protector?’ (Chandra et al 2021) in which Tom Dawson is the lead author, is a significant article and one to which we would like to draw attention. The study had two main objectives; firstly, to advance our understanding of Malassezia  in the context of pathogenicity, commensalism, and mutualism, and secondly to share what we know about microbe-microbe and host-microbe interactions. The skin fungal population is almost always overlooked, as over the last decade the focus has been primarily on 16S rRNA sequencing specific to bacteria. However, fungi are increasingly found to be important for human health and disease. Consequently, work to uncover the importance of this microbe is extremely important and valuable.   What we know Commonly published articles reference that skin is occupied by 90-95% bacteria. However, this misrepresents the proportion of the microbial community, as it counts the number of genomes. As Malassezia  are huge compared to bacteria, Malassezia  have 200-500 times the cellular biomass per genome relative to Staphylococcus epidermidis , a representative and common skin bacterium. Hence, they have similar biomass to bacteria on the sebaceous areas, for example places like the forehead where there is a lot of oil and lipids. Moreover, Malassezia  have haploid genomes of 8-9Mb, emphasizing how well adapted they are to their specific environment and which makes them have among the smallest genomes for free-living fungi. Malassezia  genomes encode lipases, phospholipases, and acid sphingomyelinases for utilisation of lipids, and proteases for utilisation of proteins. Thus, they are equipped with everything they need to be able to survive on our skin. Lipases secreted by Malassezia  decompose the human skin sebum-derived lipids, such as mono-, di-, and triglycerides, into saturated and unsaturated fatty acids. The saturated fatty acids, which are healthy for skin, are consumed by Malassezia  for survival, whereas the unsaturated fatty acids accumulate on the stratum corneum. One theory is that this accumulation might interfere with the permeability of the skin barrier thereby leading to various skin disorders. One such example of this is scalp dandruff. In this article the Malassezia  clade is subdivided into three major groups; Group A, Group B, and Group C. Group A are considered M. furfur -like, are more robust in culture, less frequent inhabitants of human skin, and more often linked to skin or septic disease. Group B are common on healthy human skin, with M. restricta  and M. globosa  by far the most common and found on the skin of all humans, followed by M. sympodialis, then distantly by the other Group B members. The Group B exception is M. pachydermatis , which can cause human septic infections but is only normally found on animal skin.  Group C are divergent Malassezia, found specifically on animal species such as rabbit ears and bats.  Phylogenetic tree for Malassezia species, taken from Chandra et al 2021. Malassezia  in Ageing Skin The amount of Malassezia  on skin changes throughout a person's lifetime. At birth, neonatal sebaceous glands are turned on by hormones present in the maternal circulation and therefore produce lipids supporting initial Malassezia  colonization and growth until around 3 months. Malassezia  then decrease in number as the sebaceous glands shut down from lack of stimulatory androgens. Upon puberty androgen secretion increases, sebaceous glands turn back on, and the Malassezia  population again takes over. This sebaceous activity is slowly lost with the decline of androgen stimulation during adulthood, where skin is typically drier. This effect is particularly apparent during menopause.   A depiction on the amount of Malassezia present on the skin over a lifetime, Sequential. As Malassezia  are among the major commensal fungi in neonates, it is hypothesised that they may also induce and establish specific immune tolerance pathways, involving regulatory T cells (Tregs), in essence “training” our immune systems as to what is “self” and what is not (Dhariwala et al 2021). So, early exposure to Malassezia  is critical in training our immune system to be familiar with Malassezia , as we need Malassezia  as a commensal or protective mutualist on our skin. Importantly, this happens regardless of whether birth is vaginal or via caesarean. Malassezia  in Skin Disease Differently from the gut and the gut microbiome, healthy skin has a low microbial diversity dominated by a very few species: Malassezia , C acnes , and healthy Staphylococcus . Keratinocytes sense microbial populations through recognition of microbial pathogen-associated molecular pattern (PAMP) motifs via their pattern recognition receptors (PRRs), leucine rich repeat (LRRs) containing receptors, and Toll-like receptors (TLRs). These initiate a cascade of inflammation, signalling to the immune system to secrete antimicrobial peptides that can rapidly inactivate any pathogenic microorganisms. Malassezia  is associated with multiple different skin diseases, with conditions either being caused or exacerbated by alterations by Malassezia  in changing skin. One possible mechanism of Malassezia  mediated skin disease is host genetic susceptibility. In this hypothesis, an underlying genetic difference in individuals causes the same Malassezia  or their metabolites to be toxic to some people, but not others. For example, a defect in skin barrier properties might mean a toxin could penetrate and cause trouble in people with susceptibility but not in others. In this case the same Malassezia  and metabolites could be present on both individuals, but only one be affected. This is common in many fungal mediated diseases and has been clearly demonstrated in dandruff (DeAngelis et al 2005).    When there are even mild barrier defects, Malassezia  can cause the common skin condition pityriasis versicolor, this is most commonly associated with M. furfur, M. globosa  and M. sympodialis . There is increasing evidence about the role of Malassezia  in inflammatory skin conditions, such as atopic dermatitis and psoriasis. Malassezia metabolites trigger a scalp inflammatory response causing dandruff, and in severe situations seborrheic dermatitis, and can invade and inflame hair follicles to cause folliculitis. Moreover, infantile seborrheic dermatitis associated with M. furfur  shows a scaling scalp, ‘cradle cap’, which may be improved by an antifungal shampoo (although this is not a particularly targeted approach). Outside of the skin field, the contribution of Malassezia  has now been found in conditions like Crohn’s disease (Limon et al 2019), and cancers such as pancreatic cancer (Aykut et al 2019), demonstrating the importance of this microbe in the fine balance of human health.   Future Directions  Looking towards the future, an improved understanding of the host- Malassezia  relationship offers potential for the development of treatments to improve skin health outcomes. In a more cosmetic context, there is also opportunity to develop and introduce prebiotic or post-biotic metabolites to restore healthy skin microbiome, to normalize skin microbiome diversity, and restore functional attributes such as barrier, dryness, inflammation, and reverse dysbiosis. Thus, giving the healthy microbes which already live on our skin the right environment and the right nutrients may be used to improve skin health. However, there are still question marks and issues with using probiotics on the skin, and we are still yet to see the engineering of a beneficial probiotic in the context of Malassezia , bearing in mind here that it was only in the 2000s that Malassezia  was first genetically engineered because it was indeed so difficult to do so. Ultimately, we conclude that more research is needed to address the mechanistic processes in fungal-fungal, and microbe-host for skin health and disease, but are hopefully awaiting future developments in this fast-moving arena.    References Aykut, B., Pushalkar, S., Chen, R. et al. (2019). The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574, 264–267. https://doi.org/10.1038/s41586-019-1608-2   Dhariwala, M., and T Scharschmidt (2021) Baby’s skin bacteria: first impressions are long-lasting. Trends Immunol., https://doi.org/10.1016/j.it.2021.10.005 Limon JJ, Tang J, Li D, Wolf AJ, Michelsen KS, Funari V, Gargus M, Nguyen C, Sharma P, Maymi VI, Iliev ID, Skalski JH, Brown J, Landers C, Borneman J, Braun J, Targan SR, McGovern DPB, Underhill DM. (2019). Malassezia Is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Models. Cell Host Microbe. 2019 Mar 13;25(3):377-388.e6. doi: 10.1016/j.chom.2019.01.007. Epub Mar 5. Vijaya Chandra, S. H., Srinivas, R., Dawson, T. L., Jr, & Common, J. E. (2021). Cutaneous Malassezia: Commensal, Pathogen, or Protector?. Frontiers in cellular and infection microbiology, 10, 614446. https://doi.org/10.3389/fcimb.2020.614446 Yvonne M. DeAngelis, Christina M. Gemmer, Joseph R. Kaczvinsky, Dianna C. Kenneally, James R. Schwartz, Thomas L. Dawson. (2005). Three Etiologic Facets of Dandruff and Seborrheic Dermatitis: Malassezia Fungi, Sebaceous Lipids, and Individual Sensitivity. Journal of Investigative Dermatology Symposium Proceedings. https://doi.org/10.1111/j.1087-0024.2005.10119.x . ( https://www.sciencedirect.com/science/article/pii/S0022202X15526146 )

The skin microbiome is influenced by various environmental factors, with ultraviolet (UV) exposure being a significant one. Current research is exploring the impact of UV rays on the skin microbiome and developing innovative solutions to prevent sun damage while preserving the microbiome's delicate balance. What We Know: Certain bacteria and fungi have been observed to respond to UV exposure by producing melanin as a protective measure. These include species such as Cladosporium spp., Sporothrix Schenckii and Cryptococcus neoformans (Woo et al., 2022). A study recruited 21 participants who spent at least 7 days in a sunny holiday destination and compared their skin microbiome samples taken before the trip and up to 84 days after their return. The dominant bacterial phyla at all time points were Actinobacteria, Proteobacteria and  Firmicutes . However, by day 28 post-holiday, all participants exhibited significant changes in microbial beta diversity (Willmott et al., 2023). Participants identified as “sun-seekers" showed an immediate reduction in Proteobacteria  just one day after their holiday, though these levels gradually recovered over time. These results, among others, suggest that sun exposure can alter the diversity and composition of the skin microbiome, which may have downstream effects on skin health (Willmott et al., 2023). Lactobacillus crispatus  possesses UV-protective properties. However, because of the variable response of skin microbes to UV exposure, sunscreen can reduce skin microbiome diversity. One study showed that the application of SPF 20 sunscreen was correlated with a decrease in Cutibacterium acnes  levels following UV exposure (Schuetz et al., 2024). Industry Impact and Potential: Beame is soon to introduce their upcoming "Something You Mist SPF 30 Face Mist," the world’s first SPF product with stress-reducing benefits. This breakthrough formula features neurophroline, a natural active ingredient derived from the seeds of the wild indigo plant (Tephrosia purpurea) , which helps balance cortisol levels, protecting against stress-induced ageing while boosting skin brightness. Products like Beame's align with emerging skincare trends such as psychodermatology, which integrates mental wellness into skincare by treating skin conditions while also addressing their psychological impact, and neurocosmetics, which utilise active ingredients to harness the connection between the skin, nervous system and brain, aiming to enhance both skin quality and mood (Rizzi et al., 2021). Our Solution: Sequential offers a comprehensive, end-to-end microbiome product testing solution, enhanced by specialised product development and formulation services. Leveraging our deep expertise, we help businesses create innovative skin products, including topical sunscreens and photoprotective solutions, that safeguard microbiome integrity while promoting overall skin health.  References: Rizzi, V., Gubitosa, J., Fini, P. & Cosma, P. (2021) Neurocosmetics in Skincare—The Fascinating World of Skin–Brain Connection: A Review to Explore Ingredients, Commercial Products for Skin Aging, and Cosmetic Regulation. Cosmetics. 8 (3), 66. doi:10.3390/cosmetics8030066. Schuetz, R., Claypool, J., Sfriso, R. & Vollhardt, J.H. (2024) Sunscreens can preserve human skin microbiome upon erythemal UV exposure. International Journal of Cosmetic Science. 46 (1), 71–84. doi:10.1111/ics.12910. Willmott, T., Campbell, P.M., Griffiths, C.E.M., O’Connor, C., Bell, M., Watson, R.E.B., McBain, A.J. & Langton, A.K. (2023) Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity. Frontiers in Aging. 4. doi:10.3389/fragi.2023.1217635. Woo, Y.R., Cho, S.H., Lee, J.D. & Kim, H.S. (2022) The Human Microbiota and Skin Cancer. International Journal of Molecular Sciences. 23 (3), 1813. doi:10.3390/ijms23031813.

Vaginal microbiome transplantation (VMT) is an emerging treatment that aims to restore the natural balance of the vaginal microbiome, offering a promising alternative to traditional therapies for vaginal disorders. Recent studies highlight its potential to treat conditions like bacterial vaginosis, recurrent yeast infections, sexually transmitted infections (STIs) and preterm birth. What We Know: The vaginal microbiome is typically acidic (pH < 4.5) due to the presence of lactic acid-producing Lactobacilli . This acidity creates a protective barrier with microbicidal and virucidal properties, preventing infections and reducing the risk of issues such as STIs, infertility and pregnancy complications (Turner et al., 2023). Therefore, disruption of this microbial balance, whether by a shift in resident bacteria or the introduction of pathogens, can lead to discomfort and inflammation (Meng, Sun & Zhang, 2024). Due to the parallels between the gut and vaginal microbiomes - both maintaining health through a balanced microbial environment and experiencing infections when disrupted - research has explored similar therapeutic approaches. Just as faecal microbiota transplantation (FMT) has been effective for gut disorders, VMT shows promise in restoring microbial balance and improving health outcomes in women with vaginal microbiome dysbiosis (Meng, Sun & Zhang, 2024). Industry Impact and Potential: Research links reduced Lactobacillus  dominance and increased vaginal microbiome diversity to precancerous lesions and cervical cancer. The microbiota associated with HPV, dysplasia or cancer includes bacteria from bacterial vaginosis and other dysbiosis. These findings suggest that VMT might aid cervical cancer treatment by restoring healthier vaginal microbiota and addressing HPV-related factors (Łaniewski, Ilhan & Herbst-Kralovetz, 2020) . Freya BioSciences has successfully completed a Phase I clinical trial of FB101, a microbiome treatment derived from healthy donors designed to boost Lactobacillus levels and address vaginal dysbiosis in women undergoing IVF. The treatment demonstrated lasting effects for over 8 weeks and improved inflammatory markers, showing promise for enhancing infertility outcomes, as dysbiotic vaginal microbiomes are linked to lower IVF pregnancy rates. Phase II trials are expected to conclude by 2025 (Smith, 2023).  Our Solution: Sequential leads the way in microbiome research, providing comprehensive services that extend beyond vaginal microbiome analysis. We also design and support studies focused on the skin, scalp and oral microbiomes while assisting your company in formulating products that protect microbiome health. Our team of experts is dedicated to helping your business develop thorough and effective studies - such as those aimed at nurturing and enhancing the vaginal microbiome - ultimately promoting women's health and well-being. References: Łaniewski, P., Ilhan, Z.E. & Herbst-Kralovetz, M.M. (2020) The microbiome and gynaecological cancer development, prevention and therapy. Nature Reviews. Urology. 17 (4), 232–250. doi:10.1038/s41585-020-0286-z. Meng, Y., Sun, J. & Zhang, G. (2024) Vaginal microbiota transplantation is a truly opulent and promising edge: fully grasp its potential. Frontiers in Cellular and Infection Microbiology. 14. doi:10.3389/fcimb.2024.1280636. Turner, F., Drury, J., Hapangama, D.K. & Tempest, N. (2023) Menstrual Tampons Are Reliable and Acceptable Tools to Self-Collect Vaginal Microbiome Samples. International Journal of Molecular Sciences . 24 (18), 14121. doi:10.3390/ijms241814121.

Atopic Dermatitis (AD) is a chronic inflammatory skin condition marked by skin barrier dysfunction and immune dysregulation. Influenced by genetic, immunological and environmental factors, as well as the skin microbiome, AD often occurs alongside food allergies (FA). Research has investigated how the skin microbiome contributes to this. What We Know: The 'Dual Allergen Exposure Hypothesis' posits that dermal exposure to allergens during the early life period can lead to FA development, whereas early consumption of allergenic foods promotes tolerance (Lack et al., 2003) . During AD flare-ups, the skin microbiome composition changes: microbial diversity decreases as disease severity increases and generally the abundance of Staphylococcus aureus significantly rises. Approximately 70% of AD individuals are colonised with S. aureus  on lesional skin and 30%–40% in non-lesional skin. Staphylococcus epidermidis  communities are present in both flare and post-flare states (Totté et al., 2016) . Industry Impact and Potential: Mouse studies have shown that FA can develop through skin exposure to allergens due to compromised skin barriers in AD. This involves immune cell activation, increased allergen-specific antibodies and inflammation. Exposure to staphylococcal toxin (SEB) and allergens results in stronger allergic responses than exposure to allergens alone, suggesting that SEB may enhance food allergy development through AD-affected skin (Savinko et al., 2005) . AD children colonised by S. aureus  have a higher risk of FA compared to healthy controls. Infants aged 4-60 months colonised by S. aureus  have an increased risk of developing peanut and egg allergies within their first 5 years, regardless of AD severity (Jones, Curran-Everett & Leung, 2016; Tsilochristou et al., 2019) .  A deeper understanding of how the skin barrier and microbiome contribute to the development of AD and FA has sparked interest in skin-based interventions for allergy prevention. Several randomised controlled trials have examined prophylactic skin interventions from infancy to prevent AD, yielding mixed results. Future research should investigate how early-life shifts in skin microbiota affect AD and FA onset to refine intervention strategies and identify microbial biomarkers for high-risk infants. Although using skin microbes as biotherapeutics for AD shows promise, further investigation is needed to assess its potential for sustained clinical benefits  (Tham et al., 2024) . Our Solution: At Sequential, we specialise in comprehensive Microbiome Product Testing tailored to meet your specific goals in formulating products, such as AD and FD treatment and prevention strategies. Our customised services empower businesses to confidently develop topical solutions. We facilitate microbiome studies to ensure these products maintain microbiome integrity, promoting efficacy and compatibility for healthier skin.  References: Jones, A.L., Curran-Everett, D. & Leung, D.Y.M. (2016) Food allergy is associated with Staphylococcus aureus colonization in children with atopic dermatitis. Journal of Allergy and Clinical Immunology. 137 (4), 1247-1248.e3. doi:10.1016/j.jaci.2016.01.010. Lack, G., Fox, D., Northstone, K. & Golding, J. (2003) Factors Associated with the Development of Peanut Allergy in Childhood. New England Journal of Medicine. 348 (11), 977–985. doi:10.1056/NEJMoa013536. Savinko, T., Lauerma, A., Lehtimäki, S., Gombert, M., Majuri, M.-L., Fyhrquist-Vanni, N., Dieu-Nosjean, M.-C., Kemeny, L., Wolff, H., Homey, B. & Alenius, H. (2005) Topical Superantigen Exposure Induces Epidermal Accumulation of CD8+ T Cells, a Mixed Th1/Th2-Type Dermatitis and Vigorous Production of IgE Antibodies in the Murine Model of Atopic Dermatitis1. The Journal of Immunology. 175 (12), 8320–8326. doi:10.4049/jimmunol.175.12.8320. Tham, E.H., Chia, M., Riggioni, C., Nagarajan, N., Common, J.E.A. & Kong, H.H. (2024) The skin microbiome in pediatric atopic dermatitis and food allergy. Allergy. 79 (6), 1470–1484. doi:10.1111/all.16044. Totté, J.E.E., van der Feltz, W.T., Hennekam, M., van Belkum, A., van Zuuren, E.J. & Pasmans, S.G.M.A. (2016) Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta‐analysis. British Journal of Dermatology. 175 (4), 687–695. doi:10.1111/bjd.14566. Tsilochristou, O., Toit, G. du, Sayre, P.H., Roberts, G., Lawson, K., et al. (2019) Association of Staphylococcus aureus colonization with food allergy occurs independently of eczema severity. Journal of Allergy and Clinical Immunology. 144 (2), 494–503. doi:10.1016/j.jaci.2019.04.025.

Introduction: What are nanoparticles? Nanoparticles (NPs) are particles with sizes ranging from 1 to 100 nanometers and can be categorized based on their properties, shapes, or sizes. Their nanoscale dimensions and large surface area make them possess unique physical and chemical characteristics. These attributes make NPs ideal for a wide range of applications, including enhancing catalysis, imaging, biomedical uses, energy research, and environmental technologies (Khan et al ., 2019). Examples of some naturally occurring nanoparticles are Silver (Ag), Gold (Au), Iron Oxide (Fe3O4), and Silica (SiO2). Ag can be found in aquatic environments and are used for their antimicrobial properties in products like plastics, paints, and cosmetics. Au are found in ore deposits and are utilized in tumor phototherapy, immunoassays, and biosensors. Fe3O4 are present in sediments and are employed in controlled drug release systems. SiO2, which can be released during volcanic eruptions or found naturally in rocks, sand, soil and water, are used as food additives, in cellular imaging, and as nanocarriers (Griffin et al ., 2017). NPs can be engineered to interact with biological systems at both the molecular and cellular levels. This precise interaction makes them highly promising tools for influencing and modulating the microbiome.  Nanocarriers Nanocarriers (NCs) are nanoengineered, biocompatible materials or devices designed to work in combination with bioactive compounds. They play a crucial role in pharmaceutical and also in cosmetic sciences by enhancing the delivery and efficacy of therapeutic agents (Rout et al ., 2018). For instance, NCs enhance drug delivery by ensuring that antifungal medications are more effectively targeted to the infection site, improving their therapeutic impact. Their small size allows for better skin penetration as well as a controlled and sustained release of drugs, which maintains therapeutic levels longer and reduces the frequency of application. Additionally, nanocarriers improve the bioavailability of poorly soluble drugs and minimize systemic side effects by focusing the drug action more precisely on the infected areas (Keshwania et al ., 2023). Bioconjugated nanoparticulate systems are now being employed in the treatment of a range of severe and previously incurable infectious diseases, including tuberculosis, as well as chronic conditions like diabetes and various types of cancers (Rout et al ., 2018). Challenges in modulating the skin microbiome Rising Antimicrobial Resistance A significant challenge in skin microbiome management is the development of antimicrobial resistance. For instance, many Cutibacterium acnes  strains, a common skin bacterium associated with acne, have developed resistance to major antibiotics such as erythromycin, clindamycin, doxycycline, trimethoprim/sulfamethoxazole, and tetracycline (Alkhawaja et al ., 2020). Stability and Competition of Applied Microbiota Stabilizing applied bacteria on the skin is challenging. Despite initial topical disinfection, it is difficult to eliminate the existing subcutaneous microbiota. Consequently, new microbiota applied to the skin surface must compete with the microbiota residing in deeper skin layers, which can undermine their effectiveness (Callewaert et al ., 2021). Technical Difficulties in Probiotic Delivery Delivering probiotics effectively presents its own set of challenges: limited concentrations, low viability in harsh environments, susceptibility to oxidative damage, challenging preservation and distribution, etc. Encapsulation technology offers a solution by enabling precise and controlled release of probiotics at varying concentrations. This method protects probiotics from harsh conditions and environmental factors such as oxygen, temperature, and light, enhancing their survival and functionality (Pandey  et al ., 2024). Advances of nanotechnology in biomedical applications To address these challenges nanotechnology has been advancing rapidly, particularly in the development of innovative drug delivery systems. Innovations in nanocarrier systems, such as nanoparticles and liposomes (Figure 1), are now engineered to specifically target pathogens or infected tissues (Zong et al ., 2022). Liposomes can carry both water-soluble (Figure 1a) and fat-soluble (Figure 1b) drugs in one structure. They are biocompatible, biodegradable, low in toxicity, and cause minimal immune response. Different types of liposomes can be made positively charged, negatively charged, or neutral (Figure 1c). Liposomes interact with cells mainly through endocytosis (Figure 1d) or fusion (Figure 1e). Additionally, they can easily be modified with surface appendages allowing them to target molecules like antibodies, proteins, or enzymes to direct drugs to infection sites (Figure 1f) (Zong et al ., 2022). NP as Transdermal drug delivery systems (TDDS) The transdermal drug delivery system is a technique that allows drugs to be absorbed through the skin. Nevertheless, the great hydrophobicity and physiology of the skin layers prevent the passive permeation of drug molecules over 500kDA, thus limiting transdermal drug diffusion. Nanoparticles have the ability to improve drug bioavailability, drug penetration and physical stability alongside providing precise dose control and targeted delivery, ensuring that drugs are released in a controlled manner and directed specifically to desired tissues or skin layers. This improved targeting helps in overcoming the skin barrier, thus enhancing treatment efficacy and reducing side effects (Palmer & DeLouise., 2016). Drugs can penetrate the stratum corneum (SC) through two primary pathways: the transepidermal route and the transappendageal route (Figure 2). Transepidermal route In the transepidermal route, drugs can penetrate the skin via two pathways: the transcellular route , which is a direct path through corneocytes and lipid layers, and the intercellular route , which involves diffusing through the lipid matrix around corneocytes. Hydrophilic drugs typically use the transcellular route, while lipophilic  drugs prefer the intercellular route (Barnes et al ., 2021).  While lipophilic and amphiphilic molecules favour the intercellular route, the architecture of the epidermis presents a difficult path to follow causing limited permissibility. However, skin penetration enhancers (e.g. DMSO, glycols, laurocapram, etc.) can enhance drug permeation. The transcellular pathway on the other hand would be unfavorable for most drugs as they would be required to alternate hydrophilic and lipophilic regions.    Transappendagel route The transappendageal route involves drug transport through sweat glands and hair follicles, creating channels across the SC. While these appendages cover only about 0.1% of the skin's surface and contribute minimally to drug absorption, they are crucial for ions and large polar molecules. Sweat ducts and sebaceous glands can limit drug permeation due to their hydrophilic and lipid-rich environments (Barnes et al ., 2021). Notwithstanding, they benefit from accelerated transport through the skin and can serve as a reservoir for the drugs for an improved and sustained controlled localised release into skin in addition to a great proximity to the capillary vessels, facilitating systemic delivery. How can nanoparticles be used to modulate the microbiome? Nanocarriers as delivery systems Delivery of antimicrobial agents NPs can be engineered to carry antimicrobial agents like antibiotics, antimicrobial peptides, or essential oils, delivering them directly to targeted areas of the skin to combat harmful microbes. For instance, silver nanoparticles are known for their broad-spectrum antimicrobial properties, effectively inhibiting the growth of various bacteria and fungi. This makes them valuable in treating skin infections, as they can disrupt microbial cell membranes, inhibit enzyme activity, and generate reactive oxygen species (ROS) that lead to microbial death (Yin et al ., 2020). Assisting probiotic delivery Encapsulating probiotics within protective nanocarriers acts as a physical barrier that shields them from harsh environments, such as stomach acid and bile, ensuring higher survival rates upon consumption. This encapsulation also protects probiotics from external factors like temperature and light during storage, enhancing their stability and shelf life. Additionally, nanocarriers enable the precise and controlled release of probiotics at targeted sites, maximizing their therapeutic potential. Co-encapsulation is also an option, where probiotics and other bioactive compounds are delivered together, potentially enhancing overall health benefits through synergistic effects (Pandey et al ., 2024). Targeted drug delivery NPs can be engineered for specific cell, tissue, or location targeting by modifying their surface with ligands or antibodies, allowing for precise delivery of therapeutic agents directly to the intended site. This targeted approach significantly limits off-target effects, reducing damage to healthy cells and minimizing bystander effects. Additionally, the enhanced targeting and delivery efficiency provided by NPs enable a reduction in the required dose of the therapeutic compound, improving safety, and conserving biocompounds (Afzal et al ., 2021). Hussain et al. (2018) accomplished this by conjugating a 9 amino acid oligopeptide to a porous silicon NP loaded with antibiotic targeting specifically S. aureus  infected tissues.  Disruption of biofilms A biofilm is a collection of microbial cells attached to a surface, encased in a matrix of extracellular polymeric substances (Donlan et al ., 2002).  Following are few metal NPs that are known to have strong defence mechanism to combat biofilm formation;  Immunomodulation There are four types of immunomodulatory nanosystems: organic , inorganic , biomimetic , and naturally derived . Organic nanosystems, such as liposomes and polymeric nanoparticles, are known for their biocompatibility and controlled release capabilities. Inorganic nanosystems, including metal and silica nanoparticles, offer stability and can directly interact with immune cells. Biomimetic nanosystems mimic natural biological structures, enhancing cellular uptake and immune response. Naturally derived nanosystems use compounds from natural sources, like plant extracts or microbial products, providing inherent biocompatibility and immunomodulatory properties (Khatun et al ., 2023). Case study: Probiotic-based nanoparticles for targeted microbiota modulation and immune restoration in bacterial pneumonia (Fu et al ., 2022) Fu et al. designed probiotic-based nanoparticles called OASCLR by coating chitosan (CS), hyaluronic acid (HA), and ononin onto living Lactobacillus rhamnosus (LR). This probiotic was chosen by virtue of its microbial competitiveness, its ability to modulate the immune response in hyperactive immunocompetent and immunocompromised hosts and its role as a modulator of the microbiome composition. To ensure the viability of LR in the lungs, the probiotic was first encapsulated in CS, known for its unique mucoadhesive properties and great biocompatibility. HA was then added as it can regulate the immune system by specifically targeting pro-inflammatory M1 macrophages via CD44 receptors. To alleviate the oxidative damage rising from the harsh conditions in the lungs, the isoflavone Ononin was added to the coating. Through ROS-scavenging, anti-inflammatory and anti-oxidant properties, ononin could enhance OASCLR’s resistance against ROS-mediated cytotoxicity and hyaluronidase degradation while also promoting the growth of LR and inhibiting pathogens. Considering the low bioactivity of LR in the ROS environment, the designed CS/HA–ononin shell could prevent LR from oxygen damage and allow OASCLR nanoparticles targeting pro-inflammatory macrophages by the interaction of HA with CD44.  These nanoparticles demonstrated over 99.97% antibacterial efficiency against common clinical pathogens. Notably, OASCLR modulated lung microbiota by reducing pathogens and enhancing the richness and diversity of probiotic and commensal bacteria. They also targeted inflammatory macrophages via CD44, alleviating excessive immune responses in hyperactive pneumonia. Additionally, OASCLR improved macrophage phagocytic function in immunocompromised pneumonia, increasing phagocytic ability from 2.61% to 12.3%. This work suggests a promising strategy for treating both hyperactive and immunocompromised bacterial pneumonia (Figure 3) (Fu et al ., 2022). Method To determine whether the lung microbiome was altered following OASCLR treatment, the study established a primary pneumonia model in mice using Staphylococcus aureus  (SA). The experimental design involved infecting mice with SA via nasal intubation on Day -3. The mice were then treated with either PBS as a negative control or OASCLR through non-invasive aerosol inhalation on Day 0. Blood tests were conducted on Days 1 and 7, and 16S ribosomal RNA gene sequencing was performed on Day 2 to analyze changes in the lung microbiome (Figure 4) (Fu et al ., 2022). Results: Modulation of lung microbiome by OASCLR OASCLR group exhibited a higher Chao richness index, indicating greater bacterial species richness (Figure 5D). Further analysis showed a shift in microbiota composition, with increased Firmicutes and decreased Proteobacteria  and Bacteroidota  (Figure 5E). Additionally, OASCLR reduced pathogenic bacteria like Staphylococcus  while boosting probiotic and commensal bacteria such as Lactobacillus  and Bifidobacterium , suggesting that OASCLR effectively promotes a healthier lung microbiota (Figure 5F) (Fu et al ., 2022). Results: Decreased inflammation Immunofluorescence analysis revealed that OASCLR treatment reduced CD45 and TNF-α expression while slightly increasing IL-10, indicating a decrease in pro-inflammatory responses. RT-PCR analysis also showed a decreased TNF-α to IL-10 ratio in the OASCLR group compared to PBS (Figure 6). These results suggest that OASCLR effectively modulates excessive inflammation in primary bacterial pneumonia (Fu et al ., 2022). Results: Macrophage polarization OASCLR treatment altered the immune landscape by reducing pro-inflammatory markers such as TNF-α and increasing anti-inflammatory IL-10. It also lowered the expression of CD80, a marker associated with M1 macrophages, which are typically involved in pro-inflammatory responses and tissue damage. They suggested that (This indicates that)  OASCLR promotes a shift towards M2 macrophages, which are known for their anti-inflammatory properties, enhanced phagocytosis, and role in tissue repair and regeneration. This change in macrophage polarisation suggests that OASCLR helps reduce inflammation and supports tissue healing (Fu et al ., 2022). Results: Biocompatibility The mice treated with OASCLR showed no significant tissue damage or adverse effects. Blood tests and H&E staining confirmed that OASCLR nanoparticles did not affect liver or kidney function and were safe for major organs. These findings suggest OASCLR has strong therapeutic potential for treating hyperactive immunocompetent primary pneumonia while complying to biocompatibility requirements (Fu et al ., 2022). Conclusion of the case study OASCLR nanoparticles were reported to restore host immunity, regulate lung inflammation, and enhance macrophage phagocytosis in bacterial pneumonia. The ononin shell allows immune evasion and safe clearance, supporting clinical use. Combining probiotics with biomaterials boosts their function, making OASCLR nanoparticles a potential treatment for various diseases beyond pneumonia (Fu et al ., 2022). Consideration of NPs for microbiome modulation Challenges in using NPs for microbiome modulation include meeting strict regulatory standards, achieving precise targeting to avoid off-target effects, and ensuring NPs stability during storage and administration. It is also important to understand the NPs degradation to ensure timely and effective drug release. These factors are critical for advancing NP-based therapies in clinical settings (Wang et al ., 2017). Conclusion: Small entities for a big future NPs have a potential to significantly impact antimicrobial therapy and microbiome modulation despite their tiny size. NPs' unique properties, such as their ability to target specific pathogens and modulate biological systems, position them as powerful tools for advancing medical treatments. This perspective underscores the transformative possibilities of NPs in addressing current challenges in healthcare, including antibiotic resistance and precise drug delivery (Wang et al ., 2017). References Afzal Shah, Saima Aftab, Jan Nisar, Muhammad Naeem Ashiq, Faiza Jan Iftikhar,  Nanocarriers for targeted drug delivery, Journal of Drug Delivery Science and Technology, Volume 62, 2021, 102426, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2021.102426 . ( https://www.sciencedirect.com/science/article/pii/S1773224721001064 ) Ali SG, Ansari MA, Alzohairy MA, Alomary MN, AlYahya S, Jalal M, Khan HM, Asiri SMM,  Ahmad W, Mahdi AA, El-Sherbeeny AM, El-Meligy MA. Biogenic Gold Nanoparticles as Potent Antibacterial and Antibiofilm Nano-Antibiotics against Pseudomonas aeruginosa . Antibiotics (Basel). 2020 Feb 27;9(3):100. doi: 10.3390/antibiotics9030100. PMID: 32120845; PMCID: PMC7148532. Alkhawaja E, Hammadi S, Abdelmalek M, Mahasneh N, Alkhawaja B, Abdelmalek SM.  Antibiotic resistant Cutibacterium acnes among acne patients in Jordan: a cross sectional study. BMC Dermatol. 2020 Nov 17;20(1):17. doi: 10.1186/s12895-020-00108-9. PMID: 33203374; PMCID: PMC7673087. Barnes TM, Mijaljica D, Townley JP, Spada F, Harrison IP. Vehicles for Drug Delivery and  Cosmetic Moisturizers: Review and Comparison. Pharmaceutics. 2021 Nov 26;13(12):2012. doi: 10.3390/pharmaceutics13122012. PMID: 34959294; PMCID: PMC8703425. 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. Donlan RM. Biofilms: microbial life on surfaces. Emerg Infect Dis. 2002 Sep;8(9):881-90. doi:  10.3201/eid0809.020063. PMID: 12194761; PMCID: PMC2732559. Fu J, Liu X, Cui Z, Zheng Y, Jiang H, Zhang Y, Li Z, Liang Y, Zhu S, Chu PK, Yeung KWK,  Wu S. Probiotic-based nanoparticles for targeted microbiota modulation and immune restoration in bacterial pneumonia. Natl Sci Rev. 2022 Oct 16;10(2):nwac221. doi: 10.1093/nsr/nwac221. PMID: 36817841; PMCID: PMC9935993. Griffin S, Masood MI, Nasim MJ, Sarfraz M, Ebokaiwe AP, Schäfer KH, Keck CM, Jacob C.  Natural Nanoparticles: A Particular Matter Inspired by Nature. Antioxidants (Basel). 2017 Dec 29;7(1):3. doi: 10.3390/antiox7010003. PMID: 29286304; PMCID: PMC5789313. Hussain, S., Joo, J., Kang, J., Kim, B., Braun, G.B., She, Z.-G., Kim, D., Mann, A.P., Mölder, T., Teesalu, T., Carnazza, S., Guglielmino, S., Sailor, M.J., Ruoslahti, E., 2018.  Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy. Nat Biomed Eng 2, 95–103. https://doi.org/10.1038/s41551-017-0187-5 Ingle AP, Duran N, Rai M. Bioactivity, mechanism of action, and cytotoxicity of copper-based  nanoparticles: a review. Appl Microbiol Biotechnol. 2014 Feb;98(3):1001-9. doi: 10.1007/s00253-013-5422-8. Epub 2013 Dec 5. PMID: 24305741. Jardeleza C, Rao S, Thierry B, Gajjar P, Vreugde S, Prestidge CA, Wormald PJ.  Liposome-encapsulated ISMN: a novel nitric oxide-based therapeutic agent against Staphylococcus aureus biofilms. PLoS One. 2014 Mar 21;9(3):e92117. doi: 10.1371/journal.pone.0092117. PMID: 24658315; PMCID: PMC3962386. Keshwania P, Kaur N, Chauhan J, Sharma G, Afzal O, Alfawaz Altamimi AS, Almalki WH.  Superficial Dermatophytosis across the World's Populations: Potential Benefits from Nanocarrier-Based Therapies and Rising Challenges. ACS Omega. 2023 Aug 22;8(35):31575-31599. doi: 10.1021/acsomega.3c01988. PMID: 37692246; PMCID: PMC10483660. Khan, Ibrahim & Saeed, Khalid & Khan, Idrees. (2019). Nanoparticles: Properties,  Applications and Toxicities. Arabian Journal of Chemistry. 12. 908-931. 10.1016/j.arabjc.2017.05.011.  Khatun S, Putta CL, Hak A, Rengan AK. Immunomodulatory nanosystems: An emerging  strategy to combat viral infections. Biomater Biosyst. 2023 Jan 30;9:100073. doi: 10.1016/j.bbiosy.2023.100073. PMID: 36967725; PMCID: PMC10036237. Palmer BC, DeLouise LA. Nanoparticle-Enabled Transdermal Drug Delivery Systems for  Enhanced Dose Control and Tissue Targeting. Molecules. 2016 Dec 15;21(12):1719. doi: 10.3390/molecules21121719. PMID: 27983701; PMCID: PMC5639878. Pandey, R.P., Gunjan, Himanshu et al.  Nanocarrier-mediated probiotic delivery: a systematic  meta-analysis assessing the biological effects. Sci Rep  14, 631 (2024). https://doi.org/10.1038/s41598-023-50972-x Rout GK, Shin HS, Gouda S, Sahoo S, Das G, Fraceto LF, Patra JK. Current advances in  nanocarriers for biomedical research and their applications. Artif Cells Nanomed Biotechnol. 2018;46(sup2):1053-1062. doi: 10.1080/21691401.2018.1478843. Epub 2018 Jun 7. PMID: 29879850. Trivedi R, Upadhyay TK, Kausar MA, Saeed A, Sharangi AB, Almatroudi A, Alabdallah NM,  Saeed M, Aqil F. Nanotechnological interventions of the microbiome as a next-generation antimicrobial therapy. Sci Total Environ. 2022 Aug 10;833:155085. doi: 10.1016/j.scitotenv.2022.155085. Epub 2022 Apr 6. PMID: 35398124. Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and  prospects for the future. Int J Nanomedicine. 2017 Feb 14;12:1227-1249. doi: 10.2147/IJN.S121956. PMID: 28243086; PMCID: PMC5317269. Yin IX, Zhang J, Zhao IS, Mei ML, Li Q, Chu CH. The Antibacterial Mechanism of Silver  Nanoparticles and Its Application in Dentistry. Int J Nanomedicine. 2020 Apr 17;15:2555-2562. doi: 10.2147/IJN.S246764. PMID: 32368040; PMCID: PMC7174845. Zong TX, Silveira AP, Morais JAV, Sampaio MC, Muehlmann LA, Zhang J, Jiang CS, Liu SK.  Recent Advances in Antimicrobial Nano-Drug Delivery Systems. Nanomaterials (Basel). 2022 May 29;12(11):1855. doi: 10.3390/nano12111855. PMID: 35683711; PMCID: PMC9182179.

In the UK, around 120,000 people visit A&E annually due to burn injuries, with 72% resulting in hypertrophic scarring, a type of raised scar that forms within the boundaries of the original wound due to excessive collagen production during healing. While traditional wound dressings effectively promote healing, there’s growing interest in innovative approaches that address post-burn scarring more effectively.  What We Know: Traditional dressings help close and heal wounds by providing hydration and antimicrobial protection, but they aren’t designed to prevent or treat post-burn scarring. Burns disrupt the skin’s microbial balance, favouring heat-loving microbes like Aeribacillus, Caldalkalibacillus  and Nesterenkonia  while reducing beneficial bacteria such as Cutibacterium, Staphylococci and Corynebacteria . Increased levels of Corynebacterium  are linked to higher infection risks, whereas Staphylococci and Cutibacterium  are associated with lower infection rates post-burn (Yang et al., 2024).  Despite reduced bacterial richness at the genus level, burn patients exhibit increased microbial community diversity and evenness. This altered microbial landscape, marked by a lower overall bacterial burden and an overgrowth of Staphylococcus  species, highlights a persistent dysbiotic state in the skin microbiota during the subacute phase of wound healing (Liu et al., 2018) . Industry Impact and Potential: @Healome Therapeutics has developed a groundbreaking bioactive skin dressing technology, recently cleared by the @Medicines and Healthcare products Regulatory Agency (MHRA) for a phase I trial aimed at reducing scarring. The trial, conducted at Queen Elizabeth Hospital in Birmingham, UK, involves 25 patients with burns covering 3-20% of their body surface. Healome’s innovative dressing is a clear film that not only offers the benefits of traditional wound dressings but also incorporates synthetic human-derived decorin protein, which plays a critical role in wound healing. This protein reduces the inflammatory response and regulates the wound’s microenvironment. Early research suggests that this approach may reduce fibrosis and promote tissue regeneration, offering new hope for scar management in burn patients. Products like Healome’s dressing showcase the exciting potential of using the microbiome and skin environment to enhance wound healing, paving the way for future innovations in burn care. Our Solution: At Sequential, we offer comprehensive services for evaluating product impacts and formulations, supported by a vast database of over 20,000 microbiome samples and 4,000 ingredients, along with a global network of more than 10,000 testing participants. Our customizable microbiome studies simulate real-world testing scenarios, ensuring that your products preserve biome integrity while delivering optimal results. References: Liu, S.-H., Huang, Y.-C., Chen, L.Y., Yu, S.-C., Yu, H.-Y. & Chuang, S.-S. (2018) The skin microbiome of wound scars and unaffected skin in patients with moderate to severe burns in the subacute phase. Wound Repair and Regeneration: Official Publication of the Wound Healing Society [and] the European Tissue Repair Society. 26 (2), 182–191. doi:10.1111/wrr.12632. Yang, Y., Huang, J., Zeng, A., Long, X., Yu, N. & Wang, X. (2024) The role of the skin microbiome in wound healing. Burns & Trauma. 12, tkad059. doi:10.1093/burnst/tkad059.