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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.

Folliculitis decalvans (FD) is a rare and challenging type of alopecia that leads to hair follicle inflammation, resulting in hair loss and scarring. Recent research suggests that FD has a unique microbiological signature and is associated with an impaired immune response, opening new avenues for understanding and treating this condition. What We Know: FD typically presents as a slowly expanding, painful alopecic plaque on the vertex of the scalp, often in young males. Despite extensive research, the exact cause is unclear. However, several factors have been implicated, including genetic predisposition, Staphylococcus aureus  colonisation, bacterial biofilms, compromised epidermal barrier integrity, congenital abnormalities in follicular orifices and dysfunction in the local immune system (Moreno-Arrones et al., 2023). As there is no definitive cure for FD, the goal of treatment is to stabilise the disease. Current therapeutic options include topical and systemic corticosteroids, antibiotics and isotretinoin. Case reports also highlight unconventional therapies such as topical tacrolimus, photodynamic therapy (PDT), dapsone, intravenous immunoglobulin (IVIG) and TNFα inhibitors, though these treatments are supported by limited evidence (Rózsa et al., 2024). Interestingly, while S. aureus  colonisation has long been linked to FD, recent research suggests its role may have been overstated due to past limitations in microbiological techniques. New studies reveal that FD-affected hair follicles have a distinct microbiome, with key species including Ruminococcaceae, Agathobacter  sp., Tyzzerella  sp. and Bacteroidales vadin  HA21 (Moreno-Arrones et al., 2023). Additionally, FD patients show significantly lower levels of IL-10, TNF-α and IL-6 after exposure to bacterial strains, indicating an impaired immune response that could contribute to the disease (Moreno-Arrones et al., 2023). Industry Impact and Potential: A successful case study treated a therapy-resistant FD patient with CO2 laser-assisted PDT. PDT induces fibroblast apoptosis, generates reactive oxygen species and offers antimicrobial and anti-inflammatory effects. Applying CO2 laser before PDT enhances photosensitiser absorption by creating microscopic channels in the skin. This method, previously effective for hypertrophic acne scars (Rózsa et al., 2024). Our Solution: With over 20,000 microbiome samples and 4,000 ingredients in our extensive database, along with a global network of more than 10,000 testing participants, Sequential offers comprehensive services to assess the impact of products and formulations. Our commitment to preserving microbiome integrity makes us an ideal partner for developing scalp and hair care products, including those focused on FD and scarring treatments. References: Moreno-Arrones, O.M., Garcia-Hoz, C., Del Campo, R., Roy, G., Saceda-Corralo, D., Jimenez-Cauhe, J., Ponce-Alonso, M., Serrano-Villar, S., Jaen, P., Paoli, J. & Vano-Galvan, S. (2023) Folliculitis Decalvans Has a Heterogeneous Microbiological Signature and Impaired Immunological Response. Dermatology (Basel, Switzerland). 239 (3), 454–461. doi:10.1159/000529301. Rózsa, P., Varga, E., Gyulai, R. & Kemény, L. (2024) Carbon-dioxide laser-associated PDT treatment of folliculitis decalvans. International Journal of Dermatology. 63 (9), 1256–1257. doi:10.1111/ijd.17136.

Menopause represents a significant hormonal shift, and its impact on the vaginal and vulvar microbiomes remains an area of emerging research. Given the prevalence of menopause-related conditions, understanding these changes is critical for advancing women's health and the treatment thereof. What We Know: Menopause introduces systemic symptoms and distinct changes in the vaginal microbiome, primarily driven by reduced estrogen levels. This reduction often leads to a decline in the dominant and favourable Lactobacillus  species, increasing the risk of microbial dysbiosis which is associated with further health complications including bacterial vaginosis, aerobic vaginitis, vulvovaginal candidiasis and increased risk of sexually transmitted infections (Muhleisen & Herbst-Kralovetz, 2016). Estrogen plays a vital role in regulating the vaginal microbiological environment by maintaining epithelial thickness and glycogen levels, promoting mucus secretion and lowering vaginal pH via Lactobacilli  colonisation and lactic acid production (Barrea et al., 2023) . These changes, along with shifts in the gut and oral microbiomes during menopause, are hypothesised to contribute to the development of menopause-related diseases, including osteoporosis, breast cancer, endometrial hyperplasia, periodontitis and cardiometabolic disorders. Therefore, interventions and solutions are crucial (Barrea et al., 2023) . Industry Impact and Potential: Hormone replacement therapy (HRT) has been shown to enhance Lactobacillus dominance in the vaginal microbiome, alleviating symptoms of dysbiosis. However, the negative side effects of HRT experienced by some patients mean that alternatives to this are necessary (Muhleisen & Herbst-Kralovetz, 2016) . Oral and vaginal probiotics hold great promise. Initial studies complement previous research findings on the menopause-vaginal microbiome connection, but additional trials are needed to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis (Muhleisen & Herbst-Kralovetz, 2016) . In one study, a two-week oral supplementation with four Lactobacillus  species (two capsules daily) positively influenced vaginal microbiota colonisation in 22 postmenopausal patients undergoing chemotherapy for breast cancer. Although this is a small sample size, it highlights the potential of probiotic treatments (Marschalek et al., 2017) . Our Solution: In addition to vulvar microbiome analysis, we at Sequential provide services for assessing skin, scalp and oral microbiomes. We have established our company as a leader in facilitating the assessment and development of products that maintain microbiome integrity. Our team of experts is well-equipped to support your company in formulating innovative products and studies aimed at maintaining and improving the vulvar microbiome to support women’s health. References: Barrea, L., Verde, L., Auriemma, R.S., Vetrani, C., Cataldi, M., Frias-Toral, E., Pugliese, G., Camajani, E., Savastano, S., Colao, A. & Muscogiuri, G. (2023) Probiotics and Prebiotics: Any Role in Menopause-Related Diseases? Current Nutrition Reports. 12 (1), 83–97. doi:10.1007/s13668-023-00462-3. Marschalek, J., Farr, A., Marschalek, M.-L., Domig, K.J., Kneifel, W., Singer, C.F., Kiss, H. & Petricevic, L. (2017) Influence of Orally Administered Probiotic Lactobacillus Strains on Vaginal Microbiota in Women with Breast Cancer during Chemotherapy: A Randomized Placebo-Controlled Double-Blinded Pilot Study. Breast Care (Basel, Switzerland). 12 (5), 335–339. doi:10.1159/000478994. Muhleisen, A.L. & Herbst-Kralovetz, M.M. (2016) Menopause and the vaginal microbiome. Maturitas. 91, 42–50. doi:10.1016/j.maturitas.2016.05.015.

The vaginal microbiome undergoes profound changes during pregnancy, marked by shifts in microbial composition and diversity that significantly impact maternal health. While the importance of these shifts is increasingly recognised, the tools to interpret these changes remain limited. What We Know: The vaginal microbiome plays a pivotal role in pregnancy, with a healthy state predominantly featuring Lactobacillus  species. These bacteria help maintain a low pH, protecting against infections. Microbial dysbiosis is linked to complications such as preterm birth (PTB), miscarriage, gestational diabetes mellitus (GDM), preeclampsia and chorioamnionitis (CAT) (Gerede et al., 2024) . PTB is associated with increased levels of anaerobic bacteria like Gardnerella vaginalis and Prevotella . Communities dominated by L. iners  or anaerobic bacteria carry higher risks compared to  L. crispatus -dominant profiles. Similarly, miscarriage often correlates with reduced Lactobacillus  abundance and greater microbial diversity. Dysbiosis not only disrupts the protective functions of the microbiome but also promotes inflammation and tissue damage, which can contribute to complications such as cervical insufficiency or placental ischemia (Gerede et al., 2024) . In GDM, altered microbiota may exacerbate inflammatory pathways, worsening glucose intolerance. Elevated levels of Prevotella bivia  have been implicated in inflammation associated with preeclampsia, while a diverse microbiome depleted of L. crispatus  is linked to increased infection risks in CAT. These microbial shifts reflect dynamic interactions with maternal physiology and evolve across pregnancy trimesters (Parraga-Leo et al., 2024) . Industry Impact and Potential: Probiotic interventions to restore Lactobacillus  dominance show promise for managing bacterial vaginosis, but their efficacy in preventing broader pregnancy complications warrants further investigation. New evidence suggests that microbial profiles and community disruptions could serve as biomarkers for identifying high-risk pregnancies (Parraga-Leo et al., 2024). Recent innovations include the Vaginal Microbiome Atlas during Pregnancy (VMAP), which integrates data from 11 studies and 3880 samples across 1402 individuals. This comprehensive resource leverages MaLiAmPi, a cutting-edge phylogenetic tool implemented via a Nextflow pipeline, to harmonise diverse datasets. By addressing technical variations and improving accuracy, MaLiAmPi enhances the reliability of microbiome data, setting a new standard for microbiome analysis (Parraga-Leo et al., 2024). Our Solution: Sequential specialises in microbiome analysis, offering services for assessing the vulvar microbiome alongside skin, scalp and oral microbiomes. Our expertise in developing products that maintain microbiome integrity positions us as industry leaders in supporting innovations for women’s health.  References: Gerede, A., Nikolettos, K., Vavoulidis, E., Margioula-Siarkou, C., Petousis, S., Giourga, M., Fotinopoulos, P., Salagianni, M., Stavros, S., Dinas, K., Nikolettos, N. & Domali, E. (2024) Vaginal Microbiome and Pregnancy Complications: A Review. Journal of Clinical Medicine. 13 (13), 3875. doi:10.3390/jcm13133875. Parraga-Leo, A., Oskotsky, T.T., Oskotsky, B., Wibrand, C., Roldan, A., et al. (2024) VMAP: Vaginal Microbiome Atlas during Pregnancy. JAMIA open. 7 (3), ooae099. doi:10.1093/jamiaopen/ooae099.

Introduction The human microbiome is a significant driver of human health and disease, composed of trillions of microorganisms that contribute to supporting host health and development. While various factors play a role in influencing the overall diversity and composition of these communities, little remains known regarding the driving factors determining their inheritance and establishment (Benga et al. , 2024). Two main competing hypotheses exist to explain this: either the human microbiome is actively shaped by (1) host genetics, or (2) maternal transmission. Many studies seeking to resolve them have achieved mixed results, making it difficult to conclude on which is the primary driver of microbial inheritance. Regardless, recent findings on the skin and gut microbiomes now suggest that host genotype might play a more important role in the active shaping of certain microbial communities than initially thought (Benga et al. , 2024). Importance of the skin and gut microbiomes As the largest organ of the human body, the skin employs a variety of chemical, physical, and biological defences to protect the body from external stress or damage by acting as a barrier to infection, promoting thermoregulation, and preventing water loss (Smythe and Wilkinson, 2023). As an extra layer of protection, it has also evolved a specialised community of symbiotic microorganisms to carry out additional functions pertaining to human skin health known as the skin microbiome. With a density of 104  to 106 bacteria per square centimetre of skin surface (Cundell, 2018), it plays an essential role in promoting skin health by preventing growth of pathogens, priming the immune system to differentiate harmful microbes from friendly ones (Lunjani et al. , 2021), and even regulating skin growth and development (Meisel et al. , 2018). The gut is another key organ that possesses its own highly diverse and interconnected community of microorganisms, reaching densities as high as 1012 cells per gram depending on segment (Sekirov et al. , 2010). These microbes line the inner walls of the gastrointestinal tract like the stomach, small, and large intestine, where they aid in carrying out essential functions involving development of the human nervous (Dash, Syed and Khan, 2022) and immune systems, influencing host metabolic activity, fermenting food, and defending against pathogens (Hou et al. , 2022).  Influence of host genotype Several factors influence human microbiome composition over the course of an individual’s life. In most cases, these forces can act to introduce new species, increase or decrease their abundance, or completely wipe them out, which can affect host health in either a positive or negative direction. While we have a fairly comprehensive understanding of the environmental and endogenous factors modulating gut (e.g., immune system, diet) and skin (e.g., cosmetics, hormones) microbiome composition, less is known regarding the key factors influencing the active shaping of these communities in early life. So far two possible hypotheses have been proposed: (1) host genetics actively shape the microbiome, or (2) microbial inheritance occurs through maternal transmission.  Evidence that all humans (to date) share over 50 bacterial species across their gut microbiota despite other compositional differences is taken as evidence that there exists a core human gut metagenome responsible for preserving these groups across the human population (Boccuto et al. , 2023). Host-genetics are theorised to influence establishment of the gut microbiome through specific genes. Although the mechanisms of how it does so is not so well understood, some evidence points to these genes influencing certain physiological factors in the host body that affect gut landscape and resulting growth of microbes. For example, one study reported a strong association between the lactase gene and levels of Bifidobacterium , a bacterium that has evolved to digest sugars found in human and cow milk, with lactose-intolerant individuals possessing a higher abundance of this bacteria than lactose-persisters (Qin et al. , 2022). This is thought to be because their inability to metabolise lactose makes this sugar more easily available for consumption by bacteria in the gut compared to persisters that can break it down on their own, thus increasing their population (Goodrich et al. , 2016). As with the gut, microbial communities on the skin are thought to be influenced at some level by host genetic factors, albeit if similarly (if not more) understudied, with studies pointing to the influence of these genes on skin architecture (Si et al. , 2015) and its associated immune system (Srinivas et al. , 2013) affecting the ability of certain species to colonise the skin surface. For example, one study found a significant link between genetic variants related to deficient skin barrier function and an abundance of Corynebacterium jeikeium , a skin bacterium responsible for causing infection in immunocompromised patients, suggesting an impaired skin barrier results in poorer defence against pathogenic bacteria like C. jeikeium  that permit it to invade and cause disease more easily (Si et al. , 2015). Influence of maternal transmission Other sources point to the early establishment of an individual’s gut microbiota being primarily driven by maternal inheritance, with mode of delivery (vaginal or caesarean) being the main mechanism through which this occurs, however, the extent of its influence over the gut microbiome remains controversial. Some studies state vaginally-delivered infants possess more species characteristic of the mother’s vaginal ( Lactobacillus + Bacteroides ) and fecal microbiota ( Bifidobacterium ), while those delivered via C-section have a greater abundance of skin microbes such as Staphylococcus  (Wang et al. , 2024). However, these findings are inconsistent across studies, and some even suggest these effects are short-lived, with compositional differences between the two groups dropping to <2% within 5 years of an infant’s life (Bogaert et al. , 2023). Other proposed means by which maternal legacy shapes the gut microbiome is through breastfeeding, which transfers essential nutrients and beneficial microbes from the mother’s milk microbiome to the infant gut (Tian et al. , 2023), or placental transmission (Miko et al. , 2022) of microbes and microbial metabolites from the mother’s gut to the infant’s to seed the gut and prime the fetus’s primitive immune system to distinguish between friendly and harmful microbe strains. Similarly, mode of delivery has also been found to play a role in influencing the establishment of bacterial and fungal communities present on the infant skin, with one study reporting vaginally-born children possess more vagina-associated fungal groups ( Candida  and Rhodotorula ) than caesarean-delivered children that possess more skin-associated and airborne fungal genera ( Malassezia  and Alternaria ) (Wang et al. , 2022). Other studies have also reported differences in the bacterial composition of vaginally and caesarean-delivered children, with the former possessing more vaginal bacteria like Lactobacillus , and latter a greater abundance of skin bacteria, like  Staphylococcus, Corynebacterium , and Cutibacterium , indicating some level of influence in delivery mode in influencing skin microbiome abundance for the first 10 years of life (Dominguez-Bello et al. , 2010). Other studies however, have noted that microbial richness, diversity, or taxonomic profiles do not significantly differ between the cutaneous microbiomes of the two infant groups in the four weeks after birth (Pammi et al. , 2017), or even between vaginally and caesarean-delivered infants aged 1–3 months (Capone et al. , 2011). These observations are believed to be attributed to the highly dynamic nature of the newborn skin microbiome that resolves these differences over time, and also highlight the inconclusive nature of this data. Study: The host genotype actively shapes its microbiome across generations in laboratory mice (Benga et al.,  2024) Existing literature regarding the effects of maternal legacy (i.e., passage through the birth canal, weaning, coprophagy, and grooming) and host genotype on human microbiomes remain inconclusive. This study set out to determine which of the two factors plays a more important role in actively shaping host microbiome composition over several generations within a controlled setting, being one of the first studies to both look at host genotype effects on skin-based communities, and maternal effects across multiple generations, providing greater insight into its longer-term influences (Benga et al. , 2024).  Results The team collected early-stage embryos from two different mice strains, and by carefully controlling the environment to minimise its effect on the mice, bred them for six generations. The first generation of offspring were exposed to a common initial microbiome to observe how the effects of host genetics and maternal legacy would go on to alter composition over the next five generations, and disentangle these factors (Benga et al. , 2024). Figure 1: Schematic representation of microbiome inheritance across six generations of mice. (1) The study investigates whether microbiome composition is primarily shaped by maternal transmission or host genetics. (2) In early generations, maternal legacy plays a dominant role in microbiome composition. (3) Over successive generations, the influence of maternal transmission diminishes, and host genotype becomes the primary factor shaping microbiome structure, as indicated by the balance shifting from maternal legacy (blue) to host genotype (yellow) in later generations. Image taken from   (Benga et al., 2024). As illustrated in Figure 1, maternal legacy had a strong effect in shaping microbiome composition within the first generation of offspring, particularly for gut-based communities. However, its influence over both skin and gut microbiome composition weakened over time and was gradually overpowered by host genotype across subsequent generations. By F3 to F5, genetic factors became the dominant force in determining microbiome structure, as represented by the shifting balance in the schematic diagram. The study identified 33 microbial species that preferentially colonized hosts of specific genetic backgrounds, indicating genotype-specific enrichment of particular taxa. Furthermore, quantification of blood serum metabolites revealed significant differences in microbial metabolite abundance between host genotypes, suggesting an interaction between host genetics and microbiome function (Benga et al. , 2024). Conclusion The study suggests that under controlled environments, host genetic traits far outweigh any maternal impact on the gut microbiome, with genotype driving the active shaping of the host microbiome over several generations under controlled environmental factors. These effects could also possibly extend to the metabolic activity of the microbiome being modulated by host genetic factors, thus further shaping its behaviour and function. The study resolves the debate by showing that maternal legacy does not persist beyond the initial offspring generation in stable environments. This study by Benga et al. (2024) stands out as one of the few researches to explore both the effects of host genotype and the maternal influences on the microbiome. However, it is essential to acknowledge that findings from mice models may not fully translate to human physiology. Therefore, future studies should aim to replicate this research in human populations to better understand how host genotype and maternal effects interact to shape the microbiome.  Strengths and limitations Strengths: Improving our understanding of the factors modulating the composition and behaviour of the human microbiome has important implications for the identification of host disease markers and abnormal species growth that can interfere with microbiome function to cause disease, allowing the development of measures that mitigate against these host genotype-driven effects (Benga et al. , 2024) Understanding the factors influencing infant microbiomes and their role in the subsequent development of early immunity can catalyse the development of novel prebiotic/probiotic therapies that prevent pathogen colonisation and infection in vulnerable infant populations (Pammi et al. , 2017) Developing multi omic platforms that can analyse the metagenomic composition of individuals in relation to other components such as proteomics and metabolomics can help identify any genetic markers that could be associated with a dysbiotic microbiota and offer personalised solutions to help counteract and balance these effects  Limitations: Many of the studies looking into disentangling the effects of maternal and host genetic influence on microbiome composition remain inconclusive regarding the effects of either, with many studies concluding on the influence of host genotype being performed on immune defective or highly inbred mice, or lacking natural process of microbiome colonisation, instead relying on artificial methods not representative of actual microbial exposure in human infants (Benga et al. , 2024) These studies also fail to consider sites other than the gut microbiome, leaving a scarcity of information regarding the influence of maternal and host-specific factors on other communities in the body such as the skin, thus preventing any meaningful conclusions being drawn from gut-specific studies More longitudinal studies are needed to establish a stronger long-term link between these factors and their influence on human microbiomes, with most host genotype studies using murine models that may not accurately reflect human physiology, behaviours, and life history processes/child-rearing practices Implications & Applications Development of therapies to maintain the health of the microbiome in susceptible populations or reverse the dysbiotic effect of faulty genetics Knowledge of how maternal influence can affect microbiome and resulting infant health can empower caregivers to practice microbiome-friendly child rearing where possible, or encourage the development of similarly beneficial alternatives if not Combining genetics and microbiome screening approaches can allow for more accurate models to be drawn to predict individual therapeutic drug responses when treating dysbiotic microbiomes (Sanna et al. , 2022) Related Research and Future Directions Application of experiments seeking to establish a more causal relationship between host genotype and microbiome composition via studies implementing controlled interventions (e.g., genetic knock-outs, germ-free hosts) to better understand the genetic mechanisms controlling microbiome composition (Bubier, Chesler and Weinstock, 2021) Expanding upon the respective roles of maternal legacy and host genotype in influencing microbiome composition and shaping at other body sites such as the vaginal and oral microbiomes to understand how these can influence overall health and disease progression Extend this to see how host genotype can influence the relationship between microbiome dysbiosis and psychological health by studying the relationship between host genetics, microbiome composition, and any psychiatric disorder-associated phenotypes or endophenotypes Conclusion The skin and gut both harbour trillions of microbes that play a crucial role in the maintenance of health and regular bodily function, with numerous factors contributing to their composition. Host genotype is likely to prevail over the effects of maternal legacy when determining the initial formation and establishment of these microbial communities in early life, with maternal legacy effects only persisting in a single generation, after which they are overpowered and persisted by the host’s own genetic factors. Expanding these studies to other bodily sites, and more longitudinal ones, can help elucidate the extent to which these factors persist in their influence, as well as how they interact with or drive disease phenotypes (Benga et al. , 2024). At Sequential, we are at the forefront of microbiome research, revolutionizing the field through its innovative Multi-Omic Studies, which integrate human and microbiome analysis to uncover deeper insights into biological interactions. By employing state-of-the-art technologies, including genetic and metabolic profiling alongside advanced microbial sequencing, we provide a comprehensive understanding of how host genetics and the microbiome shape health outcomes. This multi-layered approach enables the development of science-baked formulations, enhances product efficacy, and advances personalized skincare solutions. With an extensive microbiome database and expertise in clinical testing, we are driving scientific progress in human-microbiome research. References Benga, L. et al.  (2024) ‘The host genotype actively shapes its microbiome across generations in laboratory mice’, Microbiome , 12(1), p. 256. Available at:  https://doi.org/10.1186/s40168-024-01954-2 . Boccuto, L. et al.  (2023) ‘Human Genes Involved in the Interaction between Host and Gut Microbiome: Regulation and Pathogenic Mechanisms’, Genes , 14(4), p. 857. Available at:  https://doi.org/10.3390/genes14040857 . 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