Rosacea, a chronic inflammatory skin condition, is characterised by complex interactions between the skin microbiome and host factors, with its precise pathophysiology remaining elusive. Emerging treatments are shedding light on how these microbial and immune system dynamics may be targeted for effective management. What We Know: Demodex mites, particularly D. folliculorum and D. brevis, commonly found at the base of eyelashes, have been linked to rosacea, with higher densities observed in affected individuals. While these mites are generally harmless in small numbers, they may trigger inflammatory pathways and disrupt the skin barrier, potentially exacerbating rosacea (Sánchez-Pellicer et al., 2024) . Staphylococcus epidermidis, a typically beneficial bacterium within the skin microbiome, may also exhibit virulence factors in rosacea patients, contributing to the disease's pathogenesis (Sánchez-Pellicer et al., 2024).  Ivermectin, a topical anthelmintic drug commonly used for parasitic infections, has recently gained attention in dermatology. It works by interfering with the nerve and muscle functions of parasites, but it has also been found to have effects on microbial populations in rosacea patients (Nakatsuji et al., 2024) . Industry Impact and Potential: A recent study explored the effects of ivermectin on rosacea patients, focusing on its impact on both Demodex mites and the skin microbiome. The research demonstrated that ivermectin not only reduced Demodex density but also modulated the abundance of beneficial bacteria such as S. epidermidis, suggesting a broader therapeutic effect (Nakatsuji et al., 2024) . After treatment with ivermectin, there was an increase in the relative abundance of S. epidermidis and Cutibacterium acnes on both lesional and nonlesional skin, along with improved microbial α-diversity. A significant reduction in Demodex and an increase in S. epidermidis abundance were observed specifically on lesional skin (Nakatsuji et al., 2024) . This dual-action mechanism of ivermectin presents a promising new avenue for rosacea treatment, addressing both microbial imbalances and inflammation. These findings suggest that ivermectin and similar treatments could offer a more holistic approach to managing rosacea and other inflammatory skin conditions. The study also opens doors for further research into microbiome-targeted therapies, which may revolutionize clinical practices in dermatology (Nakatsuji et al., 2024) . Our Solution: Sequential offers an end-to-end Microbiome Product Testing Solution, alongside guided product development and formulation services. Leveraging our expertise, we assist businesses in devising novel approaches to microbiome-targeted treatments for rosacea, other skin diseases and inflammatory conditions. Our goal is to help transform skin microbiome health with treatments that fundamentally support microbiome integrity. References: Nakatsuji, T., Cheng, J.Y., Butcher, A., Shafiq, F., Osuoji, O., Gallo, R.L. & Hata, T.R. (2024) Topical Ivermectin Treatment of Rosacea Changes the Bacterial Microbiome of the Skin. Journal of Investigative Dermatology. 0 (0). doi:10.1016/j.jid.2024.10.592. Sánchez-Pellicer, P., Eguren-Michelena, C., García-Gavín, J., Llamas-Velasco, M., Navarro-Moratalla, L., Núñez-Delegido, E., Agüera-Santos, J. & Navarro-López, V. (2024) Rosacea, microbiome and probiotics: the gut-skin axis. Frontiers in Microbiology. 14. doi:10.3389/fmicb.2023.1323644.

Urinary tract infections (UTIs) affect nearly half of all women during their lifetime, with post-surgical UTIs being a common complication following female pelvic surgeries. While often viewed as an unavoidable risk, emerging research highlights the vaginal microbiome's critical role in predicting and potentially mitigating UTI risk. What We Know: UTIs occur when virulent bacteria, known as uropathogens, infiltrate the urinary system. Traditionally, the gastrointestinal (GI) tract has been regarded as the main source of these bacteria. However, mounting evidence shows that the vaginal microbiome plays an equally significant role, particularly in recurrent UTIs (Naji et al., 2024) . A study of 435 urine cultures found two-thirds of bacteria shared with the gut microbiome and one-third with the vaginal microbiome, demonstrating their interconnectedness. Vaginal bacteria predominantly influence lower urinary tract infections, while gut bacteria contribute to infections higher up in the urinary system (Dubourg et al., 2020) . When the vaginal microbiome is disrupted - through douching, sexual activity or hormonal changes - the risk of UTIs increases. Pathogens such as Gardnerella vaginalis  and Group B Streptococcus  can transiently invade the bladder, triggering immune responses and increasing susceptibility to uropathogens like E. coli . Dysbiosis, particularly a reduction in protective Lactobacillus  species, has been strongly linked to recurrent UTIs (Naji et al., 2024) .  Industry Impact and Potential: Preoperative analysis of the vaginal microbiome has the potential to revolutionise UTI risk management. In a study of postmenopausal women undergoing pelvic surgery, low levels of Lactobacillus  and a higher presence of pathogens like Gardnerella vaginalis  were predictive of postoperative UTIs. This highlights the potential for microbiome screening to inform targeted interventions and pre-surgical counselling (Occhino et al., 2024) . Beyond diagnostics, microbiome-based therapeutics hold promise. For example, Lactobacillus crispatus  probiotics have shown efficacy in reducing recurrent UTIs by inhibiting pathogen colonisation and biofilm formation. These findings emphasise the need for further research into therapies that strengthen the vaginal microbiome to lower UTI risks (Naji et al., 2024).  Our Solution: At Sequential, we are committed to advancing women’s health through innovative microbiome solutions. Alongside vulvar microbiome analysis, we offer expertise in assessing skin, scalp and oral microbiomes. Our team collaborates with clients to develop cutting-edge products and research that preserve microbiome integrity and promote health. Let us partner with you to create innovative solutions that maintain the vaginal microbiome, reduce UTI risks and empower women’s health. References: Dubourg, G., Morand, A., Mekhalif, F., Godefroy, R., Corthier, A., Yacouba, A., Diakite, A., Cornu, F., Cresci, M., Brahimi, S., Caputo, A., Lechevallier, E., Tsimaratos, M., Moal, V., Lagier, J.-C. & Raoult, D. (2020) Deciphering the Urinary Microbiota Repertoire by Culturomics Reveals Mostly Anaerobic Bacteria From the Gut. Frontiers in Microbiology. 11, 513305. doi:10.3389/fmicb.2020.513305. Naji, A., Siskin, D., Woodworth, M.H., Lee, J.R., Kraft, C.S. & Mehta, N. (2024) The Role of the Gut, Urine, and Vaginal Microbiomes in the Pathogenesis of Urinary Tract Infection in Women and Consideration of Microbiome Therapeutics. Open Forum Infectious Diseases. 11 (9), ofae471. doi:10.1093/ofid/ofae471. Occhino, J.A., Byrnes, J.N., Wu, P.-Y., Chen, J. & Walther-Antonio, M.R. (2024) Preoperative vaginal microbiome as a predictor of postoperative urinary tract infection. Scientific Reports. 14 (1), 28990. doi:10.1038/s41598-024-78809-1.

Studying the skin microbiome poses unique challenges, primarily due to the complexity of replicating its intricate environment in vitro. Recent innovations are addressing these limitations, enabling more precise, ethical and impactful microbiome research. What We Know: Skin microbiome research aims to uncover microbial traits and community dynamics associated with specific conditions or changes, providing a foundation for understanding host-microbe interactions. Microbes, highly sensitive to their environment, can serve as biomarkers for skin health, disease differentiation or treatment optimisation. These studies advance our knowledge of skin biology and support therapeutic innovation (Grogan et al., 2019) . Despite their value, many skin microbes are difficult to culture due to the complexity of the skin environment and the limitations of existing techniques. As a result, culture independent methods like 16S rRNA gene sequencing and shotgun metagenomics are widely used. These approaches analyse microbial DNA directly from samples, bypassing the need for cultivation (Grogan et al., 2019). While effective at profiling microbial ratios, culture-independent methods often lack insight into molecular interactions among microbes and with their host. A multi-omics approach - integrating metagenomics, metabolomics, proteomics and lipidomics - offers a more comprehensive way to study these complex interactions (Grogan et al., 2019). Industry Impact and Potential: A significant advancement in skin microbiome research is the TUS Skin Bacteria Co-culture (TSBC) medium, introduced by Yamamoto et al. (2024). This system enables the in vitro  study of four key skin microbes - Staphylococcus epidermidis, S. capitis, Cutibacterium acnes  and Corynebacterium  - by mimicking the skin’s natural environment. The TSBC medium has shown microbial ratios similar to those on Japanese skin, demonstrating its potential for broader applications. It facilitates research into how microbiota respond to internal factors, such as physiological changes, and external influences like skincare products (Yamamoto et al., 2024) . Together, culture-independent methods like metagenomic sequencing and culture-dependent systems like TSBC provide complementary tools for skin microbiome exploration. These advances open avenues for uncovering molecular interactions, developing targeted treatments, and enhancing personalized skincare solutions. Our Solution: Sequential is at the forefront of microbiome product testing and development, offering tailored solutions to help businesses innovate microbiome-focused products. Our expertise includes advanced culture-independent methods such as shotgun metagenomic sequencing, 16S rRNA profiling and ITS profiling, customised for diverse research needs. Whether exploring the skin, oral, scalp or vulvar microbiomes, Sequential is your ideal partner in unlocking the potential of microbiome research. References: Grogan, M.D., Bartow-McKenney, C., Flowers, L., Knight, S.A.B., Uberoi, A. & Grice, E.A. (2019) Research Techniques Made Simple: Profiling the Skin Microbiota. The Journal of investigative dermatology . 139 (4), 747-752.e1. doi:10.1016/j.jid.2019.01.024. Yamamoto, I., Sekino, Y., Kuramochi, K. & Furuyama, Y. (2024) Developing an In Vitro Culture Model for Four Commensal Bacteria of Human Skin .

Introduction The crucial role of the skin microbiome in aiding the development and maintenance of host cutaneous health and immunity has been gaining gradual recognition in the field of skin microbiome science (Liu et al. , 2023). From establishing immune tolerance in early life, to producing antimicrobial compounds to combat infection, and driving wound healing to prevent entry of unwanted pathogens past the skin barrier and into the body, it is becoming increasingly clear that these skin-associated microorganisms have a direct role in impacting host cell behaviour and function during immune development.  This is further revealed through the disruption of this balance between the two symbionts triggering infection and the development of skin disorders detrimental to host skin health. Recent studies have noted a rapid increase in the incidence of chronic inflammatory disorders like that of atopic dermatitis (AD) in recent years, with much of this through to be brought about as a result of modern lifestyle changes (i.e., increased hygiene and less exposure to microbes that enrich the microbiome) that fail to provide sufficient training for the immune system in developing these tolerogenic responses against inflammation (Alkotob et al. , 2020). Therefore, understanding and filling in our existing gaps in knowledge regarding the specifics of this immune-microbiome dialogue will be key to advancing the development of effective microbe-based treatments and therapies to address these problem areas and disorders. Study No. 1: Mechanisms of microbe-immune system dialogue within the skin (Lunjani et al.,  2021) This review article set out to outline the mechanisms through which microbes on the skin interact with each other, as well as discussing the systems that drive communication between the cutaneous microbiome and host immune system, in order to understand the role of such host-microbiome interactions in maintaining skin health (Lunjani et al. , 2021). Results Resident microbes were found to overproduce antimicrobial compounds in response to an overabundance of Staphylococcus aureus , a bacterial pathogen commonly associated with the skin disorder atopic dermatitis (AD), with beneficial, protective strains of staphylococci, such as S. epidermidis  and S. hominis , producing bacteriocin peptides to inhibit their growth by disrupting normal cell function. These species are also capable of producing other types of antimicrobial peptide that achieve similar results. The secretion of phenol-soluble modulins (PSMs) and proteases by S. Epidermidis  work by disrupting the cell membrane of these bacteria and inhibiting S. aureus biofilm formation, respectively. On the other hand, S. hominis  is capable of producing lantibiotics that are also capable of disrupting cellular membranes and preventing cell wall biosynthesis (Chakraborty, Gangopadhyay and Datta, 2019), while species such as S. lugdunensis  releases the peptide lugdunin to interrupt the usual bioelectrical activity of the cell membrane, preventing functions such as energy generation and communication (Benarroch and Asally, 2020) that allow S. aureus  to survive. Furthermore, the authors note S. aureus  has developed a complex system of communication that allows individual bacterial cells to detect and respond to changes in their local environment known as quorum sensing (Moreno-Gámez, Hochberg and van Doorn, 2023). In response, several species of commensal microbes are able to produce inhibitory molecules that block this signalling through quorum quenching, which is then able to block subsequent biofilm formation and enhance host immune response to infection. In addition to describing the complex ecological interactions mediating population control within these microbial communities on the skin, the authors of the paper also explored the mechanism of modulation of the host immune system by the cutaneous microbiome. Groups of specialised immune receptors present on the surface of skin cells of the epidermis (i.e., keratinocytes) are able to detect and distinguish between different microbe-identifying components such as proteins or genetic material, which allows the host immune system to regulate microbial density and community composition by preventing unwanted growth of potential pathogens through triggering the release of antimicrobials upon detection. Commensals on the skin are also capable of engaging in complex forms of communication with these keratinocytes to alert the host to any unwanted strains and triggering their defences. For example, the PSMs secreted by S. epidermidis  can also induce the production of keratinocyte-derived antimicrobial peptides and specific inflammatory molecules by activating some of the immune receptors present on these cells. However, these bacteria are just as capable of inhibiting a pro-inflammatory response by synthesising lipoteichoic acid following epithelial injury, which instructs these skin cells to increase the function of immune cells expressing immunoregulatory and tissue repair genes that block infection and repair the wounded skin. The authors also highlighted the role of other types of antimicrobial produced by resident skin commensals. Sapienic Acid is a type of fatty acid generated upon the metabolising of sebum by groups of bacteria, with deficient production of this compound associated with atopic dermatitis, possibly owing to its action against S. aureus , which is believed to be a risk factor for this condition. Cathelicidin, a peptide that works to disrupt the cell membranes of fungal and bacterial pathogens, as well as damaging the envelope of any infecting viral agents (Currie et al. , 2016). Anti-microbial histones, a component of neutrophil immune cells that can target and kill bacteria, as well as modulating the inflammatory immune response during infection both within the cell and outside in the extracellular environment. They are able to act against specific microorganisms like S. aureus, E. coli, and C. acnes  by inducing damage to their cellular membranes (Muñoz-Camargo and Cruz, 2024). Beyond this, the skin itself possesses a group of specialised Langerhans cells that are capable of sampling the environment for any unwanted microbes to trigger an immune response upon the detection of pathogen proteins. This property is also what allows them to produce an effective priming effect upon the host immune system for specific types of microbe such as C. albicans  and S. aureus , thus increasing the speed and effectiveness of response upon infection (Lunjani et al. , 2021). Conclusion The host-microbiome interface employs several molecular and chemical mechanisms to encourage effective communication between the two partners in the context of immune modulation in order to both protect the host from unwanted pathogen colonisation and infection, and defend against microbiome disruption and competition for resources. Such disruptions could lead to unwanted adverse effects, including accelerating the onset of certain dysbiosis-associated skin disorders such as atopic dermatitis, highlighting the importance of this bilateral immune dialogue in protecting the skin (Lunjani et al. , 2021). Study No. 2: Crosstalk between skin microbiota and immune system in health and disease (Liu et al., 2023) Introduction This comprehensive meeting report published by Nature  summarised the discussions of a workshop held by the US National Institute of Allergy and Infectious Diseases to evaluate the current state of knowledge regarding the interactions between skin microbial communities and the host immune system in health and disease (Liu et al. , 2023). Results The authors of this report noted microbial colonisation of the skin supports the establishment of immune tolerance in newborns via exposure to bacterial peptides and metabolites that induces the production of commensal-specific immune cells capable of recognising members of the host’s resident microbiota to avoid triggering unwanted immune responses targeting them for removal. Additionally, the presence of lipoteichoic acid in the cell walls of certain groups of bacteria bacteria may act to regulate the function of certain subsets of the host immune system by inducing the recruitment of maturation of immune mast cells into the skin (Wang et al. , 2017), while other strains such as S. epidermidis  are capable of producing a 6- N -hydroxyaminopurine compound that actively suppresses the growth of tumour cells and subsequent development of melanoma (Nakatsuji et al. , 2018). Several speakers also made mention of the role of certain skin microorganisms in the progression of atopic dermatitis, with some gene products from S. epidermidis  such as the enzyme cysteine protease (EcpA), promoting further inflammation and progressing disease severity, suggesting a role of certain species in driving further exacerbation of symptoms associated with certain skin disorders. Other detrimental effects associated with skin microbiome dysbiosis included the presence S. aureus  bacteria delaying the resolution of cutaneous lesions caused by infection with parasites belonging to the group Leishmania , hydrolase production by Malassezia  correlating with boosted production of proinflammatory cytokines from human skin cells, as well as a possible relationship between fungal dysbiosis and primary immune deficiencies such as STAT3 hyper IgE syndrome, a disorder characterised by eczema and recurrent skin infections (Tsilifis, Freeman and Gennery, 2021; Liu et al. , 2023). Conclusions Cross-talk between members of the cutaneous microbiome and their associated host are capable of driving both the establishment of immune tolerance, as well as shaping the development of host immune cells in early stages of life. Despite bringing about these beneficial effects, pathogenic behaviours of certain strains can also exacerbate the symptoms of dysbiotic skin disorders like atopic dermatitis, as well as interfering with regular functioning of the immune system, meaning a balance must be struck between the two to ensure skin function and homeostatic immunity (Liu et al. , 2023). Study No. 3: Skin autonomous antibody production regulates host–microbiota interactions (Gribonika et al.,  2024) Introduction This study sought to investigate the extent to which antibodies are involved in driving host skin immunity by studying the symbiotic mechanisms that trigger their production and mode of action in modulating host–microbiota dialogue and preventing onset of pathogenesis in a series of mouse models exposed to various immune treatments (Gribonika et al. , 2025). Results The authors of the study reported that topical association and colonisation of the skin by the commensal microbe S. epidermidis  was able to trigger the production of specific antibodies targeting this group of bacteria for density control, with signatures of these antibody responses detected within two weeks of administration and persisting for at least 200 days post-exposure, and followed by an increase in the level of S. epidermidis -specific antibody-secreting immune cells in the bone marrow 200 days post-topical association. This represents the development of an immune memory that is capable of producing commensal-specific antibodies targeting this specific species decades after initial exposure (Khodadadi et al. , 2019). These antibodies also demonstrated extreme strain-specificity, with no cross-reactions occurring between S. epidermidis -antibodies and other closely related species of skin bacteria such as Staphylococcus aureus . Further inoculating mice with groups of bacteria they had no prior exposure to (i.e., S. aureus  or Staphylococcus xylosus ) led to the production of antibodies specifically targeting these species, demonstrating the highly precise nature of these commensal-induced antibodies in matching their targets. Production of these topical microbe-specific antibodies were predicted to be driven by a need for the host to achieve control over the commensal burden by targeting a certain proportion of these bacteria for removal to ensure these microbes remain at a low biomass on the skin surface, as well as a general strategy to prevent infection by pathogens. To verify these claims, the researchers infected a group of mice with S. epidermidis  that they had not been previously exposed to and observed the growth of bacteria in these individuals 3 days post infection. In contrast, mice previously exposed to and already associated with this bacteria displayed a much more reduced bacterial presence in their tissues, which lends support to the idea of these commensal-specific antibodies playing a role in regulating population sizes of symbionts, with these effects observed more quickly in hosts already possessing a developed immunity against these commensals due to previous exposure to the same bacteria (Gribonika et al. , 2025). Conclusion Microbial colonisation and interaction with the skin is capable of priming the host immune system upon exposure into producing commensal-specific antibodies capable of selectively targeting and modulating the population sizes of skin resident species to reduce cutaneous microbiome biomass. These findings also highlight the role of the skin as an “autonomous lymphoid organ” capable of independently mounting an immune defensive response to regulate microbial infection and prevent any uncontrolled growth that could result in pathogenesis or infection (Gribonika et al. , 2025). Strengths & Limitations Strengths : Immunodeficient individuals that possess diminished antibody production capabilities have been shown to demonstrate increased susceptibility to skin infections. Further understanding the role of the microbiome in developing the skin’s immune system can have broad implications for the development of new therapies targeting the skin’s microbiome to help improve protection and immune development by leveraging the natural immune-priming properties of the skin microflora alongside its ability to secrete various compounds that protect the skin from disease (Gribonika et al. , 2025). Further research within this field can also foster the development of new technologies for the study of skin immunity such as: germ-free and gnotobiotic mice models, stem cells, and organoids. Not only that, but this might also aid progress in other fields of skin-related research beyond human immune system-skin microbiome interactions, extending to topics like skin physiological development or cutaneous responses to environmental stress (Liu et al. , 2023). Limitations : Many knowledge gaps still remain in skin microbiome research that must be filled to accelerate progression in developing these immune therapeutic technologies. This includes addressing topics such as the interaction dynamics between the skin microbiome and two major components of the human immune system (innate vs adaptive), how the immune system is capable of identifying and distinguishing between different commensal strains, and what the major cells and signalling pathways involved in this commensal-specific immune response are (Liu et al. , 2023). Other challenges that exist more broadly in the field of skin microbiome research also include developing realistic models that more accurately represent the process of commensal skin colonisation both on the skin and within its various niches (e.g., hair follicles), as well as further studying commensal bacteria-human cell interactions on its surface to better understand the mechanistic process underlying such immune dialogues (Liu et al. , 2023). Related Research and Future Directions Assessing the potential of topical pre- and probiotics for the treatment of skin disorders can help resolve much of the conflicting information in the current literature regarding the efficacy of such microbiome-based approaches in mitigating the effects of immune disorders of the skin. This can be taken further by investigating novel pre- and probiotic formulations that deviate from traditional ones by incorporating strains of bacteria and isolated metabolites that have not been previously used (Lunjani et al. , 2021). Further identification of new commensals and microbial metabolites that function in the skin microbiome environment could help build a more comprehensive understanding of the specific mechanisms by which the host immune system and cutaneous microbiome modulate each other to accelerate progress in therapeutic development to treat skin-associated disorders, as well as identifying novel targets for these treatments (Liu et al. , 2023). Conclusions The complex dialogue between the skin and its associated microbial community plays an important role in modulating host immunity and priming the host immune system against pathogen infection, all while promoting the selective recognition of symbiotic commensals through various means such as intercellular communication, antimicrobial peptide secretion, and commensal-specific antibody production. While previous studies offer detailed insight into some of the mechanisms employed during this symbiosis to confer cutaneous immunity, further studies might want to focus on developing knowledge gaps in other aspects of this area like the influence of these microbes over other components of the immune system (and vice-versa) to facilitate the development of novel therapeutics addressing skin health concerns by harnessing the natural immunogenic properties of the skin microbiome. References Alkotob, S.S. et al.  (2020) ‘Advances and novel developments in environmental influences on the development of atopic diseases’, Allergy , 75(12), pp. 3077–3086. Available at:   https://doi.org/10.1111/all.14624 . Benarroch, J.M. and Asally, M. (2020) ‘The Microbiologist’s Guide to Membrane Potential Dynamics’, Trends in Microbiology , 28(4), pp. 304–314. Available at:   https://doi.org/10.1016/j.tim.2019.12.008 . Chakraborty, H.J., Gangopadhyay, A. and Datta, A. (2019) ‘Prediction and characterisation of lantibiotic structures with molecular modelling and molecular dynamics simulations’, Scientific Reports , 9(1), p. 7169. Available at:   https://doi.org/10.1038/s41598-019-42963-8 . Cundell, A.M. (2018) ‘Microbial Ecology of the Human Skin’, Microbial Ecology , 76(1), pp. 113–120. Available at:   https://doi.org/10.1007/s00248-016-0789-6 . Currie, S.M. et al.  (2016) ‘Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans’, The Journal of Immunology , 196(6), pp. 2699–2710. Available at:   https://doi.org/10.4049/jimmunol.1502478 . Gribonika, I. et al.  (2025) ‘Skin autonomous antibody production regulates host–microbiota interactions’, Nature , 638(8052), pp. 1043–1053. Available at:   https://doi.org/10.1038/s41586-024-08376-y . Khodadadi, L. et al.  (2019) ‘The Maintenance of Memory Plasma Cells’, Frontiers in Immunology , 10, p. 721. Available at:   https://doi.org/10.3389/fimmu.2019.00721 . Liu, Q. et al.  (2023) ‘Crosstalk between skin microbiota and immune system in health and disease’, Nature Immunology , 24(6), pp. 895–898. Available at:   https://doi.org/10.1038/s41590-023-01500-6 . Lunjani, N. et al.  (2021) ‘Mechanisms of microbe-immune system dialogue within the skin’, Genes & Immunity , 22(5), pp. 276–288. Available at:   https://doi.org/10.1038/s41435-021-00133-9 . Moreno-Gámez, S., Hochberg, M.E. and van Doorn, G.S. (2023) ‘Quorum sensing as a mechanism to harness the wisdom of the crowds’, Nature Communications , 14(1), p. 3415. Available at:   https://doi.org/10.1038/s41467-023-37950-7 . Muñoz-Camargo, C. and Cruz, J.C. (2024) ‘From inside to outside: exploring extracellular antimicrobial histone-derived peptides as multi-talented molecules’, The Journal of Antibiotics , 77(9), pp. 553–568. Available at:   https://doi.org/10.1038/s41429-024-00744-0 . Nakatsuji, T. et al.  (2018) ‘A commensal strain of Staphylococcus epidermidis protects against skin neoplasia’, Science Advances , 4(2), p. eaao4502. Available at:   https://doi.org/10.1126/sciadv.aao4502 . Tsilifis, C., Freeman, A.F. and Gennery, A.R. (2021) ‘STAT3 Hyper-IgE Syndrome—an Update and Unanswered Questions’, Journal of Clinical Immunology , 41(5), pp. 864–880. Available at:   https://doi.org/10.1007/s10875-021-01051-1 . Wang, Z. et al.  (2017) ‘Skin microbiome promotes mast cell maturation by triggering stem cell factor production in keratinocytes’, Journal of Allergy and Clinical Immunology , 139(4), pp. 1205-1216.e6. Available at:   https://doi.org/10.1016/j.jaci.2016.09.019 .

Emerging research into the oral-gut microbiome axis highlights the profound impact of these interconnected ecosystems on systemic health. Once considered distinct, the oral and gut microbiomes are now recognised for their influence on various health outcomes, opening new opportunities for innovation that optimises this relationship. What We Know: The oral cavity and gut, while separate, are linked through microbial migration, especially during dysbiosis or compromised gut barriers. Oral microbes can travel to the gut via oral-to-gut or faecal-to-oral routes, influenced by factors like low gastric acidity, poor hygiene and immune deficiencies (Park et al., 2021). Shared microbial taxa such as Streptococcus, Prevotella  and Veillonella  demonstrate this connection throughout the gastrointestinal tract (Kunath et al., 2024). Oral dysbiosis, often linked to periodontal disease, has widespread systemic effects. Pathogens like Porphyromonas gingivalis  and Fusobacterium nucleatum  contribute to conditions like inflammatory bowel disease (IBD), colorectal cancer (CRC), liver diseases and pancreatic cancer by promoting inflammation and disrupting gut barrier function (Park et al., 2021). Prolonged use of antibacterial mouthwash, like chlorhexidine, disrupts both the oral and gut microbiomes. A mouse study showed that chlorhexidine reduced weight gain and improved metabolic function, but also increased colon triglycerides, suggesting reduced nutrient absorption. While short-term effects were beneficial, potential long-term disruptions in microbiota balance and nutrient malabsorption highlight the need for careful formulation of oral care products. This illustrates the oral-gut microbiome axis' role (Carvalho et al., 2024). Industry Impact and Potential: Ongoing research is needed to clarify the complexities of the oral-gut microbiome axis. Advanced metagenomic studies will further our understanding of microbial interactions and their role in systemic diseases (Kunath et al., 2024). Microbiome therapies offer the potential for personalised medicine, targeting the oral-gut axis to treat conditions like IBD, CRC and autoimmune disorders. For example, probiotic interventions (Park et al., 2021). Oral microbiome analysis can also serve as a non-invasive, cost-effective tool for early disease detection, as science now knows this to be representative of a larger landscape (Park et al., 2021). Our Solution: At Sequential, we lead microbiome product development and testing from global hubs in London, New York and Singapore. Our customisable services empower businesses to innovate confidently, ensuring products preserve microbiome integrity while meeting efficacy and sustainability goals, and studies that explore this. Partner with us to explore optimising the oral-gut microbiome axis by oral microbiome intervention and develop cutting-edge solutions for improved health outcomes. References: Carvalho, L.R.R.A., Boeder, A.M., Shimari, M., Kleschyov, A.L., Esberg, A., Johansson, I., Weitzberg, E., Lundberg, J.O. & Carlstrom, M. (2024) Antibacterial mouthwash alters gut microbiome, reducing nutrient absorption and fat accumulation in Western diet-fed mice. Scientific Reports. 14 (1), 4025. doi:10.1038/s41598-024-54068-y. Kunath, B.J., De Rudder, C., Laczny, C.C., Letellier, E. & Wilmes, P. (2024) The oral–gut microbiome axis in health and disease. Nature Reviews Microbiology. 22 (12), 791–805. doi:10.1038/s41579-024-01075-5. 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. (2021) Oral-Gut Microbiome Axis in Gastrointestinal Disease and Cancer. Cancers. 13 (9), 2124. doi:10.3390/cancers13092124.

The vaginal microbiome undergoes cyclical changes throughout the menstrual cycle, yet little is known about how menstrual products - such as tampons, pads and menstrual cups - interact with and influence this delicate ecosystem. Gaining insights into these interactions could lead to innovations that optimise the vaginal microbiome and reduce infection risk. What We Know: The vaginal microbiome fluctuates throughout the menstrual cycle. Research shows that Lactobacillus crispatus  increases during non-menstrual phases, while bacterial vaginosis-associated species decrease, reflecting microbial shifts linked to hormonal changes (Krog et al., 2022). The reasons behind increased microbiome diversity during menstruation remain unclear, but may involve hormonal shifts, iron availability from menstrual blood or the effects of menstrual products (Krog et al., 2022). Industry Impact and Potential: Research comparing menstrual products suggests nuanced effects on vaginal health. One study found no significant differences in microbiome composition between tampon and menstrual cup users. However, menstrual cup use was linked to increased reports of fungal genital infections, though the small sample size limits the generalisability of these findings (Tessandier et al., 2023). Another study examined the impact of tampons and menstruation on vaginal microbiome composition and diversity. It found that Lactobacillus  species dominated at mid-cycle, with individualised but significant changes during menstruation. Despite some diversity differences between pad and tampon use, the two tampon types (viscose and cotton) did not significantly alter the microbiome (Hickey et al., 2013). A separate study identified tampons as a niche for Staphylococcus aureus , detected in 40% of healthy women and 100% of menstrual toxic shock syndrome cases. However, tampons did not significantly affect microbiome richness or diversity. The virulence of S. aureus  seems to stem from complex microbial interactions, rather than tampon use directly affecting the microbiome (Jacquemond et al., 2018). These findings underscore the importance of continued research into the interaction between menstrual products and the vaginal microbiome. Understanding these dynamics could lead to menstrual products that better support microbiome resilience, reduce infection risk and promote women's health. Our Solution: At Sequential, we are leading the way in microbiome research and development, offering comprehensive services beyond vaginal/vulvar microbiome analysis. We also assess skin, scalp and oral microbiomes, reinforcing our leadership in creating products that maintain microbiome integrity. Our team excels at helping companies develop robust studies to enhance the vaginal microbiome, improving women’s health and well-being. References: Hickey, R.J., Abdo, Z., Zhou, X., Nemeth, K., Hansmann, M., Osborn, T.W., Wang, F. & Forney, L.J. (2013) Effects of tampons and menses on the composition and diversity of vaginal microbial communities over time. BJOG: an international journal of obstetrics and gynaecology. 120 (6), 695–704; discussion 704-706. doi:10.1111/1471-0528.12151. Jacquemond, I., Muggeo, A., Lamblin, G., Tristan, A., Gillet, Y., Bolze, P.A., Bes, M., Gustave, C.A., Rasigade, J.-P., Golfier, F., Ferry, T., Dubost, A., Abrouk, D., Barreto, S., Prigent-Combaret, C., Thioulouse, J., Lina, G. & Muller, D. (2018) Complex ecological interactions of Staphylococcus aureus in tampons during menstruation. Scientific Reports. 8 (1), 9942. doi:10.1038/s41598-018-28116-3. Krog, M.C., Hugerth, L.W., Fransson, E., Bashir, Z., Nyboe Andersen, A., Edfeldt, G., Engstrand, L., Schuppe-Koistinen, I. & Nielsen, H.S. (2022) The healthy female microbiome across body sites: effect of hormonal contraceptives and the menstrual cycle. Human Reproduction (Oxford, England). 37 (7), 1525–1543. doi:10.1093/humrep/deac094. Tessandier, N., Uysal, I.B., Elie, B., Selinger, C., Bernat, C., et al. (2023) Does exposure to different menstrual products affect the vaginal environment? Molecular Ecology. 32 (10), 2592–2601. doi:10.1111/mec.16678.

Beef tallow has recently gained popularity as a natural solution for various skin concerns. Despite anecdotal support, scientific research on its effects - particularly on the skin microbiome - remains limited. What We Know: Historically used in cooking, soap and as a biofuel, tallow is a rendered form of suet, which is the hard fatty tissue surrounding the organs of ruminant animals like cattle and sheep. Therefore, it is essentially a byproduct of the meat industry (Russell et al., 2024) . Tallow is solid at room temperature and composed mainly of triglycerides, including oleic acid, palmitic acid, stearic acid and linoleic acid, along with essential fat-soluble vitamins A, D, E and K. Its high triglyceride content makes it an effective natural moisturising agent, often marketed as a more biocompatible alternative to petroleum-based skincare products (Russell et al., 2024) . Tallow’s composition closely mirrors that of human skin, which may explain its reported benefits for skin health. The application of physiological lipids, like those found in tallow, supports the skin’s barrier function, suggesting its use as a promising natural moisturiser with biocompatible, skin-friendly properties (Russell et al., 2024) . Industry Impact and Potential: Mutton tallow combined with walnut oil in an enzymatically interesterified fat blend has shown promising moisturising and stability properties, indicating potential therapeutic benefits for conditions like atopic dermatitis (AD) and psoriasis. Furthermore, tallow has been  (Kowalska et al., 2017) . Omega-3 beef tallow, sourced from omega-3-fed cows, is part of a therapeutic blend that has demonstrated potential for treating AD by reducing inflammation, enhancing skin barrier proteins and normalising immune responses in affected skin (Lee et al., 2020) . Some research on tallow’s use as a delivery vehicle for drugs and in vaccines exists, but studies on isolated tallow in skincare are limited. Due to the lack of regulation, consumers should be cautious about product sourcing and quality. As an animal-derived ingredient, tallow may face challenges in a market favouring plant-based and vegan products, while its lack of reef-safety and environmental impact may deter eco-conscious consumers (Russell et al., 2024) . Furthermore, research on tallow's side effects, including potential skin or eye irritation, is inconclusive, highlighting the need for further studies across different skin types (Russell et al., 2024) . Our Solution: Sequential’s personalised skincare approach leverages the power of microbiome-driven products through our comprehensive Microbiome Product Testing Solution. This all-inclusive service combines independent testing with expert-led formulation, empowering businesses to create innovative, customised skincare solutions that are tailored to the unique needs of individual microbiomes. References: Kowalska, M., Mendrycka, M., Zbikowska, A. & Kowalska, D. (2017) ASSESSMENT OF A STABLE COSMETIC PREPARATION BASED ON ENZYMATIC INTERESTERIFIED FAT, PROPOSED IN THE PREVENTION OF ATOPIC DERMATITIS. Acta Poloniae Pharmaceutica. 74 (2), 465–476. Lee, Y.-S., Yang, W.-K., Jo, E.-H., Shin, S.H., Lee, Y.-C., Park, M.-C. & Kim, S.-H. (2020) NCM 1921, a Mixture of Several Ingredients, Including Fatty Acids and Choline, Attenuates Atopic Dermatitis in 1-Chloro-2,4-Dinitrobenzene-Treated NC/Nga Mice. Nutrients. 12 (1), 165. doi:10.3390/nu12010165. Russell, M.F., Sandhu, M., Vail, M., Haran, C., Batool, U. & Leo, J. (2024) Tallow, Rendered Animal Fat, and Its Biocompatibility With Skin: A Scoping Review. Cureus. 16 (5), e60981. doi:10.7759/cureus.60981.

Orthodontic devices, like thermoplastic retainers, are vital for maintaining teeth alignment after braces or preventing grinding. However, their impact on the oral microbiome remains underexplored, and innovation is needed to mitigate potential disruptions, which can lead to microbial imbalances and infections. What We Know: The oral microbiome is shaped by factors such as diet, pH levels and microbial interactions, and orthodontic devices can disrupt this balance, raising infection risks. Retainers often accumulate plaque, but it remains unclear whether the material, surface roughness or wear duration most influences plaque retention. This disruption creates an environment that favors harmful bacteria, like Streptococcus mutans  and Lactobacillus , linked to dental caries and plaque buildup (Al-lehaibi et al., 2021). Orthodontic appliances also impact oral hygiene by reducing saliva exposure, which lowers its natural antimicrobial effect. This can increase microbial concentrations, acidity and food residue retention, promoting dysbiosis and potentially leading to periodontal disease (Al-Lehaibi et al., 2021) . Industry Impact and Potential: A study of patients wearing thermoplastic retainers for three months revealed significant changes in the oral microbiome, with Lactobacillus  species predominating, followed by Streptococcus . This microbial shift is concerning as these bacteria are associated with dental caries and plaque buildup. Excess Lactobacillus  can create an acidic environment that accelerates enamel demineralization, increasing the risk of tooth decay and other oral health issues (Al-Lehaibi et al., 2021). Advances in orthodontic device hygiene, such as ultrasonic and UVC cleaning technologies, help reduce plaque and harmful microbial buildup. These technologies not only improve oral hygiene but also maintain retainer material integrity, extending the appliance’s lifespan. Brands like @Zima Dental and @Sonic Dental offer countertop devices that use these technologies to sanitise retainers, ensuring better hygiene and mitigating microbial accumulation. Future research should focus on understanding how different retainer materials, surface textures and wear durations specifically influence the microbial composition of the oral cavity. Investigating the interaction between these factors and the development of dental diseases could help develop more effective hygiene strategies and orthodontic appliances that minimise microbiome disruption. Our Solution: At Sequential, we specialise in microbiome analysis and product development across oral, skin, scalp and vulvar microbiomes. As pioneers in creating innovative solutions to protect and preserve the microbiome, we are well-equipped to collaborate with your company to develop products that support oral health, enhance hygiene practices for orthodontic device users and reduce the risk of microbiome dysbiosis. References: Al-Lehaibi, W.K., Al-Makhzomi, K.A., Mohammed, H.S., Enezei, H.H. & Alam, M.K. (2021) Physiological and Immunological Changes Associated with Oral Microbiota When Using a Thermoplastic Retainer. Molecules (Basel, Switzerland) . 26 (7), 1948.

The skin microbiome is a dynamic ecosystem shaped by both internal and external factors. Ongoing research aims to distinguish natural fluctuations from those driven by environmental influences. What We Know: Facial skin is particularly sensitive to environmental factors like temperature, humidity and UV exposure, leading to variations in microbiome composition across different climates. For instance, UV radiation increases sebum production, promoting the growth of lipophilic microorganisms such as Cutibacterium acnes  and Malassezia , while warm temperatures (33.2–35.0°C) further support their growth by boosting sebum secretion. Higher humidity levels tend to enhance bacterial diversity (Tao et al., 2024). One study highlighted this variability, showing that individuals in northwest China’s dry, high-altitude regions had lower Malassezia  and bacterial diversity but higher ceramide and fatty acid levels compared to those living in the warm, humid southern regions (Tao et al., 2024). Industry Impact and Potential: A study tracking microbiome variability over the course of a year found that Cutibacterium  was more abundant in winter, correlating with increased transepidermal water loss (TEWL), a measure of skin barrier integrity. In contrast, Corynebacterium, Staphylococcus  and Streptococcus  were more abundant in summer. These changes in bacterial populations were linked to fluctuations in skin hydration, elasticity and TEWL (Seo et al., 2023). Interestingly, hydration levels did not show significant seasonal variation, but elasticity was higher in summer, aligning with the increased abundance of Staphylococcus  and Streptococcus . The study also revealed that TEWL was significantly higher in winter, while Cutibacterium  abundance and TEWL decreased from winter to summer (Seo et al., 2023). These findings highlight the importance of adapting skincare routines to seasonal changes to maintain microbiome health and barrier integrity. In colder months, increased TEWL from low humidity can be countered with hydrating products containing humectants like hyaluronic acid and barrier-strengthening ingredients like ceramides (Proksch, 2008). In warmer, humid conditions, lightweight, non-comedogenic products and consistent sunscreen use can manage oil levels while protecting against UV-induced microbiome shifts and barrier damage (Seo et al., 2023). Our Solution: At Sequential, we lead the way in microbiome research with a robust database of over 20,000 microbiome samples, 4,000 ingredients and a global network of 10,000 testing participants. Our solutions offer customisable microbiome studies and product formulations, with a focus on preserving microbiome integrity. Whether exploring the skin, scalp, oral or vulvar microbiome, Sequential is your ideal partner in advancing microbiome research. References: Proksch, E. (2008) Protection Against Dryness of Facial Skin: A Rational Approach. Skin Pharmacology and Physiology. 22 (1), 3–7. doi:10.1159/000159771. Seo, J.Y., You, S.W., Gu, K.-N., Kim, H., Shin, J.-G., Leem, S., Hwang, B.K., Kim, Y. & Kang, N.G. (2023) Longitudinal study of the interplay between the skin barrier and facial microbiome over 1 year. Frontiers in Microbiology. 14, 1298632. doi:10.3389/fmicb.2023.1298632. Tao, R., Li, T., Wang, Y., Wang, R., Li, R., Bianchi, P., Duplan, H., Zhang, Y., Li, H. & Wang, R. (2024) The facial microbiome and metabolome across different geographic regions. Microbiology Spectrum. 12 (1), e03248-23. doi:10.1128/spectrum.03248-23.

Introduction The vagina is one of the most heavily colonised organs of the human body, with a unique ecosystem consisting of bacteria, fungi, viruses and other groups of microorganisms that play a vital role in modulating reproductive fertility, preventing inflammatory diseases and sexually transmitted infections, and may even contain microbial biomarkers indicating risk of preterm delivery during pregnancy (Lee et al. , 2023). Its physical properties (i.e., low pH and oxygen) make it an ideal environment for specific colonisation by groups of mostly acid-favouring and low-oxygen tolerant species, resulting in a relatively low level of diversity (France et al. , 2022; Lee et al. , 2023).   In healthy, cisgender women (individuals whose gender identity is the same as their birth-assigned sex), the vaginal microbiomes is usually dominated by a single group of bacteria known as the Lactobacilli , which are capable of producing lactic acid compounds that work to maintain the acidic pH of the vagina and inhibit growth of harmful pathogens (Huang et al. , 2024). This low diversity composition is favoured within the vagina, as shifts from a Lactobacillus dominant to a more diverse microbiome are commonly associated with increased risk of disease and infection, including disorders such as sexually transmitted infections (STIs), bacterial vaginosis (BV), and even HIV (France et al. , 2022; Feil et al. , 2024). The vaginal microbiomes of transgender men Transgender men (i.e., individuals assigned female sex at birth but identify as male) who have retained their natal genitalia may also choose to undergo gender affirming hormone therapy (GAHT) in the form of testosterone supplementation to aid in presenting with a more masculine appearance through increased facial and body hair, greater muscle mass, and suppression of menstruation (Winston McPherson et al. , 2019).  While much of the focus of vaginal microbiome research has been related to cisgender women, it is also worth focusing on the properties of these communities in transgender individuals, especially those that might be undergoing testosterone therapy, as this hormone is predicted to play a strong role in influencing the composition of the vaginal microbiome with substantial effects. However, the relationship between the two remains to be fully explored, with only a couple of studies in the current literature seeking to understand it. Study No. 1: The vaginal microbiome of transgender men (Winston McPherson et al.,  2019) To better understand the effects of GAHT on vaginal microbiome composition, this study set out to investigate how testosterone would go on to influence the vaginal floras of a cohort of healthy transgender men prescribed testosterone for at least 1 year compared with samples taken from cisgender women, being one of the first studies in the field to do so (Winston McPherson  et al.,  2019). Results The researchers found the vaginal flora of most the transgender men to have a lower abundance of Lactobacillus (<2%) as the primary bacterial group inhabiting the vagina compared to the microbiomes of cisgender women (>90%), and a greater overall bacterial diversity and abundance of species such as Gardnerella  and Prevotella  associated with increased risk of bacterial vaginosis (BV).  However, transgender individuals receiving oestrogen either as a treatment for vaginal atrophy or BV showed a positive association with the majority presence of Lactobacillus  (>90%) and reduced species diversity in the microbiota, suggesting a similar effect of oestrogen in maintaining a favourable environment for Lactobacillus  colonisation and prevention of disease in transgender men. The authors go on to state that administration of intravaginal oestrogen might counteract these effects and restore balance to the vaginal microbiomes of transgender men receiving testosterone therapy (Winston McPherson  et al.,  2019). Conclusion Testosterone can act to cause compositional changes in the vaginal microflora of transgender individuals by depleting Lactobacillus  abundance and promoting the growth of bacterial species associated with bacterial vaginosis, leading to differences between cisgender women and transgender men. This study also draws a link between oestrogen and Lactobacillus , with the former promoting growth and colonisation of the vagina by the latter and reducing diversity, suggesting a possible therapy for the treatment of conditions associated with this kind of dysbiosis (Winston McPherson  et al.,  2019). Study No. 2: The vaginal microbiome of transgender men receiving gender-affirming hormonal therapy in comparison to that of cisgender women (Feil et al.,  2024) Building off results from previous studies, the aim of this was to investigate similarities between the vaginal microbiome compositions of transgender men and menopausal and premenopausal cisgender women as as the effects of hormonal testosterone therapy in the former and reduced oestrogen in the latter are believed to have a similar effects in both groups (Feil et al. , 2024). Results Analyses of microbiome composition revealed transgender men and menopausal women to possess greater species diversity than premenopausal women, with the vaginal communities of transgender men characterised by similarities to those of menopausal women, a reduction in Lactobacillus  and increase in the population of gut-associated species such as Campylobacter, Anaerococcus, Dialister, and Prevotella . However, the abundance of the latter two groups showed a decline over the duration of hormonal therapy in trans men. The authors of the study suggest these similarities between transgender men and menopausal women to be driven by a reduction of oestrogen in the blood resulting in a reduction of vaginal glycogen, a vital chemical metabolised by Lactobacillus species into lactic acid that maintains the ideal acidic environment of the vagina. As this oestrogen decreases, less glycogen is available as a food source for these beneficial bacteria, causing the population to decrease and the vaginal pH to rise as a result. This opens up room for colonisation by other species, thus causing the observed increase in species diversity, and increasing susceptibility to infection. Over time, the authors noted a reduction in this species diversity with length of testosterone treatment in transgender men, likely caused by a lowered abundance of Dialister and Prevotella  species, and suggesting a shift to a less diverse vaginal microbiome with prolonged testosterone therapy. Although they did note that Lactobacillus  populations failed to return to their original dominance even after this period (Feil et al. , 2024). Conclusion The study suggests that the reduced abundance of Lactobacillus  and overall increase in species diversity within the vaginal microbiomes of transgender men receiving GAHT to be driven by a reduction in glycogen compounds in the vagina that Lactobacillus  species use as a food source, with their subsequent loss opening up space for habitation by other species and infection, and resulting in effects similar to those in menopausal cisgender women while differing significantly from the microbiomes of premenopausal cisgender women (Feil et al. , 2024). Study No. 3: Characteristics of the Vaginal Microbiome Before and After Testosterone Treatment in Transgender Men (Panichaya et al.,  2024) Another study looking to investigate the effects of initiating testosterone therapy on the composition of vaginal microbiota in transgender men by comparing vaginal communities before and after testosterone use over the course of 12 weeks in a cohort of Thai participants, while also assessing its impact on the appearance of vulvovaginal symptoms such as vaginal pH, vaginal atrophy score (VAS), and vaginal maturation value (VMV) (Panichaya et al. , 2024). Results This study also reported a loss of Lactobacillus  dominance post-testosterone treatment, accompanied by a significant increase of Prevotella and Streptococcus . Similar to previous studies, administration of testosterone resulted in an increase in the vaginal microbiome diversity of transgender men in the post-treatment group, further lending support to the composition-altering effects of testosterone on these microbial communities.  Participants of the study reported the appearance of more vulvovaginal symptoms after 12 weeks of testosterone treatment, with higher VAS, higher vaginal pH, and worse VMVs, however these symptoms did not demonstrate any statistically significant correlation with the decreased relative abundance of Lactobacilli  observed in these groups, with the authors suggesting a potential trend that could be further elucidated through future studies with larger sample sizes. Interestingly, the study also failed to establish any significant statistical correlation between changes in hormone levels within the participants (i.e., decrease in estradiol/increase in testosterone) and reduction of Lactobacillus , another observation that merits being followed up on. While there were no reports of infection in the 12-week follow up after the study had ended, the authors predicted longer term use of testosterone might eventually cause vaginal infection and other physical symptoms (e.g., painful intercourse, itching, irregular bleeding) to emerge (Panichaya et al. , 2024). Conclusion This study demonstrated significant changes to occur in the vaginal microbiomes of transgender men undergoing testosterone therapy, including a reduction in the relative abundance of Lactobacillus  and increase in overall diversity, two symptoms commonly associated with potential adverse vaginal health outcomes. It also looked at physical effects resulting from hormonal therapy in relation to these compositional changes in the vaginal microbiota, and reported an interesting trend emerging between the two despite their lack of significant correlation (Panichaya et al. , 2024). Strengths & Limitations of Research Strengths : Improving our understanding of how testosterone therapy can influence the vaginal microbiomes of transgender men can drive the development of strategies to prevent or reduce the risk of serious infection or disease such as BV/HIV commonly associated with testosterone-altered microbial communities. This will aid in improving the quality of life and healthcare outcomes for transgender individuals undergoing GAHT, and also improve sexual health within this population. Developments in this field will also help destigmatize discussions and research surrounding vaginal health in transgender men so that individuals and healthcare professionals can accurately address concerns surrounding these topics, while also helping transgender individuals make more informed decisions regarding their health. Data from these studies can provide extensive repositories of vaginal and serum specimens collected from transgender participants that can be used by researchers as a resource to accelerate progress in fields such as disease research, drug development, and biomarker identification within the context of transgender health research (Muzny et al. , 2023). Limitations : The small sample sizes used in these studies reduces their ability to identify subtle differences between groups, draw clear correlations between hormone levels and vaginal microbiomes, while increasing the likelihood of obtaining statistical errors that could reduce the accuracy of conclusions being drawn from the data (Winston McPherson et al. , 2019). Many of the aforementioned studies also failed to collect any demographic information (race, ethnicity, or body mass index) on their participants, meaning little information could be obtained on the extent of these factors in influencing the rate or magnitude of testosterone-driven changes in vaginal microbiome composition (Winston McPherson et al. , 2019). More longitudinal studies looking into the effects of testosterone on the vaginal microflora of transgender men are needed. These will help better define the relationship between the two, and establish a stronger causal link between any observed compositional changes ( Lactobacillus  depletion; increase in diversity) and testosterone therapy, should one exist. Related Research and Future Directions The findings of these studies can be taken further through the development of therapeutic treatments to treat unwanted effects in the vaginal microbiomes of transgender individuals receiving GAHT, such as the use of vaginal or oral probiotics to prevent infection by restoring balance to the microbiome without the use of oestrogen therapy that can have potentially dysphoric effects (Feil et al. , 2024). Understanding the hormonal factors influencing the vaginal microbiome of transgender men may have potential therapeutic applications in developing approaches to restore microbiome balance in other groups. This may include those of menopausal women possessing similar compositions to transgender individuals, the neovaginal microbiomes of transgender women who have not yet started oestrogen therapy to establish these Lactobacillus  dominant communities, as well as cisgender women suffering from hormonal disorders such as polycystic ovary syndrome (PCOS) resulting in above average levels of testosterone that might cause similar microbiome shifts as those observed in transgender men. Gathering more demographic data (e.g., ethnicity/age/race) could help determine whether these factors affect how vaginal microbiomes respond to testosterone therapy and improve the generalisability of studies investigating testosterone’s influence on these microbial communities (Panichaya et al. , 2024). Conclusion The vagina is an incredibly complex organ housing trillions of microorganisms that play an essential role in its healthy development. However, many studies looking into the role of the vaginal microbiome have almost exclusively focused on these effects in cisgender women, with scarce information on how their role could be affected during gender-affirming testosterone therapy in transgender men. Despite this, recent findings suggest testosterone to be a big player in altering the composition of the vaginal microbiome from its healthy state of Lactobacillus  dominance to a more diverse one that runs the risk of causing infection or disease. More studies are needed to better understand this relationship, improve our knowledge of transgender health, and drive the development of effective treatments to minimise any risk of harm arising from these testosterone-mediated shifts in microbiome structure. References Feil, K. et al.  (2024) ‘The vaginal microbiome of transgender men receiving gender-affirming hormonal therapy in comparison to that of cisgender women’, Scientific Reports , 14(1), p. 21526. Available at:   https://doi.org/10.1038/s41598-024-72365-4 . France, M. et al.  (2022) ‘Towards a deeper understanding of the vaginal microbiota’, Nature Microbiology , 7(3), pp. 367–378. Available at:   https://doi.org/10.1038/s41564-022-01083-2 . Huang, L. et al.  (2024) ‘A multi-kingdom collection of 33,804 reference genomes for the human vaginal microbiome’, Nature Microbiology , 9(8), pp. 2185–2200. Available at:   https://doi.org/10.1038/s41564-024-01751-5 . Lee, C.Y. et al.  (2023) ‘New perspectives into the vaginal microbiome with systems biology’, Trends in Microbiology , 31(4), pp. 356–368. Available at:   https://doi.org/10.1016/j.tim.2022.09.011 . Muzny, C.A. et al.  (2023) ‘Impact of testosterone use on the vaginal microbiota of transgender men, including susceptibility to bacterial vaginosis: study protocol for a prospective, observational study’. Available at:   https://doi.org/10.1136/bmjopen-2023-073068 . Panichaya, P. et al.  (2024) ‘Characteristics of the Vaginal Microbiome Before and After Testosterone Treatment in Transgender Men’, Transgender Health  [Preprint]. Available at:   https://doi.org/10.1089/trgh.2023.0249 . Winston McPherson, G. et al.  (2019) ‘The Vaginal Microbiome of Transgender Men’, Clinical Chemistry , 65(1), pp. 199–207. Available at:   https://doi.org/10.1373/clinchem.2018.293654 .

The skin microbiome is vital for skin health and barrier integrity. Sun exposure, especially UV radiation, plays a significant role in modulating this ecosystem. While moderate sun exposure aids vitamin D synthesis, excessive UV radiation disrupts microbial balance, causing oxidative stress and altering microbial composition. Understanding the interaction between UV and the skin microbiome is crucial for advancing skincare and overall skin health. What we know: A significant shift in microbial beta diversity was observed on the forearms of participants after four weeks of extensive sun exposure compared to baseline, suggesting that sunlight alters the diversity and composition of the skin microbiota (Willmott et al ., 2023). An overall increase in Cyanobacteria , Fusobacteria , Verrucomicrobia , and Oxalobacteraceae  species was observed, while Lactobacillaceae  and Pseudomonadaceae  species showed a decline after UVR exposure (Gilaberte et al ., 2025). Research shows that bacteria, like skin cells, react differently to UVA and UVB light. One study found both UV types reduce Pseudomonas aeruginosa, but Escherichia coli was less affected by UVA, indicating varying bacterial responses to sunlight (Smith et al., 2023). A study found that SPF 20 sunscreen protects both skin and its microbiome, preventing erythema and preserving beneficial bacteria like Lactobacillus crispatus. In contrast, unprotected or placebo-treated skin showed a disrupted microbial balance, with a reduced Lactobacillus to Cutibacterium acnes ratio (Schuetz et al., 2024). Applying sunscreen prior to UV exposure helps support and protect the skin microbiome, and researchers suggest that using sunscreens with higher SPF levels could provide even stronger microbial and skin protection (Schuetz et al ., 2024). Industry impact and potential: The growing awareness of how sun exposure affects the skin microbiome is driving innovation in sun care. Research indicates that UV protection can influence the balance of skin microorganisms, paving the way for products that not only shield against sun damage but also support overall skin health. Further research is needed to understand how different UV wavelengths impact the skin microbiome and contribute to long-term skin health issues, including aging and chronic conditions. More studies are also required to evaluate how various sunscreen formulations affect the skin’s microbial balance (Gilaberte et al ., 2025). Our solution: At Sequential, we help skincare brands create sun care products that protect the microbiome and support skin health. Through in vivo testing and detailed analysis of formulations' impact on the skin’s microbial ecosystem, we ensure products deliver UV protection without disrupting microbial balance. With access to over 20,000 microbiome samples, we provide scientifically-backed solutions that meet the growing demand for skin care prioritizing long-term health and immediate benefits. References: Gilaberte Y, Piquero-Casals J, Schalka S, Leone G, Brown A, Trullàs C, Jourdan E, Lim HW,  Krutmann J, Passeron T. Exploring the impact of solar radiation on skin microbiome to develop improved photoprotection strategies. Photochem Photobiol. 2025 Jan-Feb;101(1):38-52. doi: 10.1111/php.13962. Epub 2024 May 20. PMID: 38767119; PMCID: PMC11737011. Schuetz R, Claypool J, Sfriso R, Vollhardt JH. Sunscreens can preserve human skin  microbiome upon erythemal UV exposure. Int J Cosmet Sci. 2024 Feb;46(1):71-84. doi: 10.1111/ics.12910. Epub 2023 Oct 6. PMID: 37664974. Smith, M. L., O’Neill, C. A., Dickinson, M. R., Chavan, B., & McBain, A. J. (2023). Exploring  associations between skin, the dermal microbiome, and ultraviolet radiation: advancing possibilities for next-generation sunscreens. Frontiers in Microbiomes , 2 , Article 1102315. https://doi.org/10.3389/frmbi.2023.1102315 Willmott T, Campbell PM, Griffiths CEM, O'Connor C, Bell M, Watson REB, McBain AJ,  Langton AK. Behaviour and sun exposure in holidaymakers alters skin microbiota composition and diversity. Front Aging. 2023 Aug 8;4:1217635. doi: 10.3389/fragi.2023.1217635. PMID: 37614517; PMCID: PMC10442491.

The relationship between our oral and gut microbiomes is a growing area of research, offering new insights into how these communities shape health and disease. Emerging evidence is revealing how everyday oral hygiene practices, like antibacterial mouthwash use, affect this balance. What We Know: The gut and oral microbiomes are among the body’s largest microbial ecosystems, comprising 29% and 26% of the total bacterial count, respectively. Despite their distinct environments, their two-way connection - the ‘oral-gut microbiome axis’ - facilitates the exchange of microbial signals and metabolites that influence digestion, immune responses and systemic health. Disruptions in this axis have been linked to gastrointestinal disorders, cardiovascular diseases, among others, underscoring its vital role in maintaining overall health (Carvalho et al., 2024).  Although these microbiomes are distinct - due to barriers like gastric acidity and bile - oral bacteria may sometimes bypass these defences and migrate to the gut, influencing the gut microbiome and potentially contributing to diseases such as inflammatory bowel disease (IBD), colorectal cancer and systemic inflammatory conditions (Kunath et al., 2024). Industry Impact and Potential: Prolonged use of antibacterial mouthwash has been shown to disrupt the oral microbiome. A study on Listerine Cool Mint found that daily use for three months increased levels of Fusobacterium nucleatum  and Streptococcus anginosus . These opportunistic bacteria are linked to periodontal disease, systemic illnesses and even oesophageal and colorectal cancers. Moreover, oral bacteria that bypass the gut’s barriers may trigger systemic inflammation, compromising immune function and contributing to chronic diseases (Laumen et al., 2024). Research on chlorhexidine mouthwash in mice revealed notable changes in gut health, including reduced microbiome diversity, impaired nutrient absorption, and altered metabolism. While outcomes like decreased weight gain may initially appear beneficial, they are likely a result of malabsorption, which can have harmful downstream effects (Carvalho et al., 2024). These findings highlight the need to explore the oral–gut microbiome axis further, particularly the role of the oral microbiome in gut function and nutrient absorption. This opens new possibilities for developing oral hygiene products that maintain oral microbiome integrity while safeguarding the gut microbiome, paving the way for innovative solutions that support holistic health. Our Solution: At Sequential, we lead microbiome product development and testing from our hubs in London, New York and Singapore. We help businesses create products that preserve microbiome integrity while achieving efficacy. Partner with us to develop cutting-edge oral hygiene solutions that target the oral-gut microbiome axis and advancing health outcomes. References: Carvalho, L.R.R.A., Boeder, A.M., Shimari, M., Kleschyov, A.L., Esberg, A., Johansson, I., Weitzberg, E., Lundberg, J.O. & Carlstrom, M. (2024) Antibacterial mouthwash alters gut microbiome, reducing nutrient absorption and fat accumulation in Western diet-fed mice. Scientific Reports. 14 (1), 4025. doi:10.1038/s41598-024-54068-y. Kunath, B.J., De Rudder, C., Laczny, C.C., Letellier, E. & Wilmes, P. (2024) The oral–gut microbiome axis in health and disease. Nature Reviews Microbiology. 22 (12), 791–805. doi:10.1038/s41579-024-01075-5. Laumen, J.G.E., Van Dijck, C., Manoharan-Basil, S.S., de Block, T., Abdellati, S., Xavier, B.B., Malhotra-Kumar, S. & Kenyon, C. (2024) The effect of daily usage of Listerine Cool Mint mouthwash on the oropharyngeal microbiome: a substudy of the PReGo trial. Journal of Medical Microbiology. 73 (6). doi:10.1099/jmm.0.001830.