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Acne vulgaris, affecting up to 97% of adolescents globally, is a widespread skin condition. Recent advancements in treatment are focusing on innovative topical products that specifically target the biofilm formation of Cutibacterium acnes , the primary bacterium linked to acne. What we know: Acne is characterised by increased sebum production, which leads to inflammatory lesions (papules, pustules or nodules) primarily on the face, back and chest. While C. acnes  is linked to acne, its exact role is unclear due to its widespread presence in both healthy and acne-affected skin (Cavallo et al ., 2022). C. acnes  strains are classified into six phylotypes: IA1, IA2, IB, IC, II and III, each associated with different body distributions, clinical conditions, antimicrobial susceptibility and inflammatory properties. The IA1 phylotype is predominantly found in moderate to severe acne and is notably more virulent, suggesting that the dominance of IA1 strains in acne patients may indicate a dysbiotic shift linked to microenvironmental changes within the follicle (Cavallo et al. , 2022). Biofilm production by specific C. acnes  phylotypes is linked to colonisation of the pilosebaceous unit, potentially causing a homeostatic imbalance in the skin microbiome. Biofilms in acne follicles lead to persistent bacterial presence and relapse after antibiotic treatment, indicating a strong connection to biofilm-related colonisation. While biofilm is crucial for C. acnes persistence during antibiotic therapy, the factors promoting early adhesion and biofilm formation remain unidentified (Cavallo et al ., 2022). Industry impact and potential: All  C. acnes strains can form biofilm, but phylotype IA1 is the most effective at doing so. Research has shown that IA1 strains exhibit enhanced biofilm formation capabilities, including greater adhesion, increased biomass production, and a higher degree of antibiotic tolerance compared to other phylotypes (Cavallo et al ., 2022). @Vytrus Biotech has introduced Quora Noni™, a groundbreaking product featuring anti-quorum sensing molecules derived from plant stem cells. This innovative treatment targets acne by inhibiting the formation of virulent biofilms. Dubbed "the microbiome communication hacker," Quora Noni™ disrupts the communication between the skin microbiome and epidermal cells, delivering an effective bacteriostatic and anti-biofilm effect against C. acnes. Our solution: At Sequential, we specialise in comprehensive Microbiome Product Testing tailored to meet your specific goals in formulating products, such as acne treatment and prevention strategies. Our expertise and customised services empower businesses to innovate confidently in developing topical solutions. Additionally, we facilitate microbiome studies to ensure these products maintain microbiome integrity, promoting efficacy and compatibility for healthier skin. References: Cavallo, I., Sivori, F., Truglio, M., De Maio, F., Lucantoni, F., Cardinali, G., Pontone, M., Bernardi, T., Sanguinetti, M., Capitanio, B., Cristaudo, A., Ascenzioni, F., Morrone, A., Pimpinelli, F. & Di Domenico, E.G. (2022) Skin dysbiosis and Cutibacterium acnes biofilm in inflammatory acne lesions of adolescents. Scientific Reports. 12 (1), 21104. doi:10.1038/s41598-022-25436-3.

Chemical peels are dermatological procedures that involve applying a chemical solution to the skin, thereby exfoliating the top layers to allow cell turnover and enhance skin texture and tone. The process involves using different types of acids or chemical agents that can vary in strength, leading to varying depths of peel, from superficial to deep. The procedure needs to be carried out more than once to get beneficial results, and recent research has begun to explore their impact on the skin microbiome. What we know: Chemical peels can reduce sebum production and possess antibacterial, anti-inflammatory, keratolytic, and comedolytic properties (Măgerușan et al ., 2023). 30% Supramolecular Salicylic Acid Peel have shown to decrease certain bacterial populations such as Staphylococcus and Propionibacterium (Shao et al ., 2023). A study had found out that the immediate application of the chemical peel, caused a disruption in the skin's microbial composition. However, over a period of several weeks, the skin microbiota had rebalanced to levels similar or better than pre-treatment levels, indicating a temporary disturbance followed by a recovery phase (Bhardwaj et al ., 2024). It was seen that immediately after the peel, C. acnes  decreased by 60%. However, within two weeks, these counts began to return to normal levels, reaching baseline levels by the fourth week (Bhardwaj et al ., 2024). Although the peel initially compromises the skin barrier, the recovery phase showed an improvement in barrier function, potentially due to the regrowth of a balanced microbiome (Bhardwaj et al ., 2024). Industry impact & potential: Post-peel treatments should be designed to restore and support the skin microbiome. Further studies need to be done to delve deeper into the interaction between chemical peels and skin microbiome. Our solution: Sequential is at the forefront of integrating microbiome science into skincare. Our cutting-edge research aims to analyse and understand how skincare products interact with the skin microbiome. By collaborating with us and our skincare professionals we can advise you on treatments that not only enhance skin appearance but also maintain microbiome health. Reference: Bhardwaj V, Handler MZ, Mao J, Azadegan C, Panda PK, Breunig HG, Wenskus I, Diaz I, König  K. A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face: Clinical evidence and mechanistic understanding by computational biology and optical biopsy. Exp Dermatol. 2024 Apr;33(4):e15069. doi: 10.1111/exd.15069. PMID: 38568090. Măgerușan ȘE, Hancu G, Rusu A. A Comprehensive Bibliographic Review Concerning  the Efficacy of Organic Acids for Chemical Peels Treating Acne Vulgaris. Molecules. 2023 Oct 22;28(20):7219. doi: 10.3390/molecules28207219. PMID: 37894698; PMCID: PMC10608815. Shao X, Chen Y, Zhang L, Zhang Y, Ariyawati A, Chen T, Chen J, Liu L, Pu Y, Li Y, Chen J.  Effect of 30% Supramolecular Salicylic Acid Peel on Skin Microbiota and Inflammation in Patients with Moderate-to-Severe Acne Vulgaris. Dermatol Ther (Heidelb). 2023 Jan;13(1):155-168. doi: 10.1007/s13555-022-00844-5. Epub 2022 Nov 9. PMID: 36350527; PMCID: PMC9823178.

Antibiotics are a class of antimicrobial substances designed to target and eliminate bacteria. They play a crucial role in modern medicine as the primary agents used to fight bacterial infections. These powerful medications are indispensable for both treating and preventing bacterial diseases, making them one of the most important tools in combating infectious diseases. What we know: Antibiotic treatment decreases the bacterial density and alters the bacterial composition in skin (Zhang et al ., 2014). Subjects treated with doxycycline 100mg and trimethoprim/sulfamethoxazole showed more significant alterations in skin microbial communities than those that did not receive antibiotics (Jo et al ., 2021). Oxytetracycline reduced the diversity of the skin microbiome. Diversity reduction often indicates a disruption in the natural balance of microbial communities (Pereira et al ., 2024). Exposure to antibiotics often leads to the development of antibiotic-resistant bacteria within the skin microbiome (Jo et al ., 2021). The skin microbiome has the ability to recover after antibiotic exposure, but the recovery process can be slow and incomplete. Some bacterial communities may never return to their original state, potentially leading to long-term health impacts (Jeanette et al ., 2017). Industry impact & potential: Studies show that after antibiotic treatment, resistant strains can dominate, posing a challenge for future treatments (Jo et al ., 2021). Companies can innovate by creating targeted antibiotics that minimize disruption to the beneficial microbiota or by developing products that support microbiome recovery post-antibiotic treatment The cosmetic industry can leverage this knowledge to create skincare products that promote a healthy microbiome, potentially reducing the need for antibiotics by enhancing the skin's natural defense mechanisms Our solution: At Sequential, we have the first-ever targeted skin panels, specifically designed to address key skin concerns. These panels, a breakthrough in microbiome research, reflect years of dedicated work by our scientists to identify the microbial factors behind various skin conditions. Unlike traditional microbiome research tools, our panels allow for precise, focused analysis on any specific skin concern.  Reference: Jeanette M Carlson, Annie B Leonard, Embriette R Hyde, Joseph F Petrosino & Todd P  Primm (2017) Microbiome disruption and recovery in the fish Gambusia affinis following exposure to broad-spectrum antibiotic, Infection and Drug Resistance, , 143-154, DOI: 10.2147/IDR.S129055 Jo JH, Harkins CP, Schwardt NH, Portillo JA; NISC Comparative Sequencing Program;  Zimmerman MD, Carter CL, Hossen MA, Peer CJ, Polley EC, Dartois V, Figg WD, Moutsopoulos NM, Segre JA, Kong HH. Alterations of human skin microbiome and expansion of antimicrobial resistance after systemic antibiotics. Sci Transl Med. 2021 Dec 22;13(625):eabd8077. doi: 10.1126/scitranslmed.abd8077. Epub 2021 Dec 22. PMID: 34936382; PMCID: PMC8878148. Pereira, Ana & Brown, Anya & Strobel, Davis & Soares, Marta & Xavier, Raquel & Apprill,  Amy & Sikkel, Paul. (2024). Effects of two common antibiotics on the skin microbiome of ornamental reef fishes: Implications for manipulative experiments in microbial dynamics. Aquaculture, Fish and Fisheries. 4. 10.1002/aff2.162.  Zhang M, Jiang Z, Li D, Jiang D, Wu Y, Ren H, Peng H, Lai Y. Oral antibiotic treatment  induces skin microbiota dysbiosis and influences wound healing. Microb Ecol. 2015 Feb;69(2):415-21. doi: 10.1007/s00248-014-0504-4. Epub 2014 Oct 10. PMID: 25301498.

Intense Pulsed Light or IPL is a non-invasive treatment method that uses broad-spectrum light to address various skin concerns such as acne, hyperpigmentation, rosacea, and aging. The technology functions by emitting various wavelengths of light that penetrate the skin and target specific chromophores, such as melanin in hair follicles or hemoglobin in blood vessels. This process causes the targeted chromophores to heat up and break down. Unlike lasers, an IPL device emits multiple wavelengths of pulsating light.  What we know: There are observable changes in the overall microbial diversity on the skin post-IPL treatment, with some bacterial populations decreasing and others increasing (Liu et al ., 2021). A study found that IPL treatment significantly reduced the population of Cutibacterium acnes , and thereby inhibiting sebum secretion (Liu et al ., 2021). It was also seen that the relative abundance of Staphylococcus epidermidis increased  (Liu et al ., 2021). Blue light specifically targets bacteria like Cutibacterium acnes through the generation of reactive oxygen species (ROS), IPL’s broader spectrum affects a wider range of chromophores, potentially leading to broader microbial changes (Serrage et al ., 2024). The changes in microbial populations due to IPL are often temporary, and after returns to its baseline state over time (Serrage et al ., 2024). Industry impact & potential: By influencing the skin microbiome, IPL may provide therapeutic benefits for conditions linked to microbial imbalance, such as acne and rosacea. IPL could be incorporated into treatment regimens not only for cosmetic enhancements but also for the management of chronic skin conditions, thus broadening its clinical applications. Our solution: At Sequential, we conduct skin microbiome testing for your personalised skincare products. We have a database of 20,000 microbiome samples. We also have expert researchers and dermatologists that can advice you on an ingredient or product. Reference: Liu, Jiexiong & Liu, Lu & Zhou, Lin & Chen, Lingna & Chen, Xia & Xiong, Xia & Deng,  Yongqiong. (2021). The Effect of Intense Pulsed Light on the Skin Microbiota and Epidermal Barrier in Patients with Mild to Moderate Acne Vulgaris. Lasers in Surgery and Medicine. 53. 10.1002/lsm.23426.  Serrage HJ, O' Neill CA, Uzunbajakava NE. Illuminating microflora: shedding light on the  potential of blue light to modulate the cutaneous microbiome. Front Cell Infect Microbiol. 2024 Apr 10;14:1307374. doi: 10.3389/fcimb.2024.1307374. PMID: 38660491; PMCID: PMC11039841.

Many females report using personal lubricants during intimate sexual activities to help alleviate vaginal dryness and the genitourinary syndrome of menopause. Clinicians also frequently use vaginal lubricants to conduct gynecologic exams. Lubricants are classified by the Food and Drug Administration (FDA) as medical devices, and they are subject to more regulatory control than general-use products due to their intended use in contact with sensitive skin and mucosal tissues.  What we know: Research indicates that some lubricants can disrupt the vaginal microbiome by altering its pH and microbial composition (McElroy et al ., 2016). There are a few differences in the vaginal microbiota and cytokine profiles of lubricant users and controls, and it was seen that there was a decrease in the relative abundance of Lactobacillus crispatus  following use of lubricant, which is a predominant bacteria in a healthy vaginal microbiome (Tuddenham et al ., 2021). Most clinical and personal lubricants contain parabens and chlorhexidine gluconate (CHG), and CHG have a detrimental effect on the vaginal microbiota by decreasing the overall bacterial load, including health-associated Lactobacillus  spp (Łaniewski et al ., 2021). Two commonly used brands of lubricant, Surgilube and KY Jelly, contain chlorhexidine and can alter vaginal microbiota (McElroy et al ., 2016). Water-based lubricants on the vaginal microbiome of premenopausal and postmenopausal women remained unchanged, although the vaginal microbiome differed significantly between them (Krychman et al ., 2023). Industry impact & potential: The industry is shifting towards the development of microbiome-friendly lubricants. Companies are focusing on formulations that support the natural vaginal flora, reduce irritation, and maintain optimal pH levels . Our solution: Sequential is a company dedicated to advancing microbiome research and testing formulas not only in skin, scalp, oral microbiome, but the vaginal microbiome as well. We utilize advanced genomic sequencing techniques to profile individual microbiomes, providing insights into the specific composition and health of the microbiome. We conduct human clinical trials to evaluate the efficacy and safety of products. These trials involve recruiting participants to test new formulations, ensuring real-world applicability and effectiveness  Reference: Krychman, Michael MD; Hood, Sarah BS; Palacios, Santiago MD; Soe, Jin PhD. Evaluation  of the Effect of Water-Based Lubricants on the Vaginal Microbiome of Premenopausal and Postmenopausal Women [ID: 1376703]. Obstetrics & Gynecology 141(5S):p 103S, May 2023. | DOI: 10.1097/01.AOG.0000931272.48436.ba McElroy, Katie & Regan, Mary. (2016). Vaginal Microbiota and Lubricant Use During Labor:  Implications for Nursing Research, Practice, and Policy. SAGE Open Nursing. 2. 10.1177/2377960816662286. Łaniewski P, Owen KA, Khnanisho M, Brotman RM, Herbst-Kralovetz MM. Clinical and  Personal Lubricants Impact the Growth of Vaginal Lactobacillus Species and Colonization of Vaginal Epithelial Cells: An in Vitro Study. Sex Transm Dis. 2021 Jan;48(1):63-70. doi: 10.1097/OLQ.0000000000001272. PMID: 32842049; PMCID: PMC8793461. Tuddenham S, Stennett CA, Cone RA, Ravel J, Macintyre AN, Ghanem KG, He X, Brotman  RM. Vaginal cytokine profile and microbiota before and after lubricant use compared with condomless vaginal sex: a preliminary observational study. BMC Infect Dis. 2021 Sep 18;21(1):973. doi: 10.1186/s12879-021-06512-x. PMID: 34537015; PMCID: PMC8449901.

The oral-lung axis is an emerging field of research that explores the connection between oral health and the lung microbiome. Growing evidence indicates that maintaining a healthy oral microbiome and good oral hygiene practices may play a crucial role in protecting lung health.  What We Know: The oral-lung axis is a closely linked and bi-directional connection between the oral and lung microbiomes. This relationship highlights the role of the oral microbiome in lung health and disease (Garmendia & Cebollero-Rivas, 2024). The oral microbiome is one of multiple factors that affects and challenges respiratory health. Others include host genetics, diet, lifestyle and exposure to toxicants (smoke, biofuel, pollutants) (Cicchinelli et al., 2023). The lung microbiome frequently overlaps with the oral microbiome due to the close connection between these two anatomical regions through the oral-lung axis. Salivary flow and microaspiration are the primary mechanisms that promote the establishment of the lung microbiome (Garmendia & Cebollero-Rivas, 2024). Smoking is an environmental factor that significantly alters the composition of the oral and subgingival microbiota, leading to oral dysbiosis characterised by a diverse, pathogen-rich, commensal-poor and anaerobic microbiome. These changes impact lower airway dysbiosis through the oral-lung axis, negatively affecting respiratory health (Cicchinelli et al., 2023). Industry Impact and Potential: Dental plaque migrating to the lungs can worsen lung microbiome imbalances and related diseases. For example, the periodontal pathogen Fusobacterium nucleatum in the lungs is linked to worsening Chronic Obstructive Pulmonary Disease (COPD). Conversely, COPD can also disrupt the oral microbiota. This bidirectional relationship emphasises the need for more research and suggests that improving oral health could help prevent and manage lung diseases (Garmendia & Cebollero-Rivas, 2024). Researchers urge dentists and physicians to be more aware of the oral microbiome's impact on COPD and other lung diseases. They emphasise the need to prevent periodontal disease and slow the progression of COPD by monitoring and addressing oral health (Subbappa et al., 2023). Interventional studies have demonstrated that periodontal treatments aimed at supporting the oral microbiome can help improve symptoms of COPD, prompting development of innovative products to support oral health (Lin et al., 2023). Our Solution: At Sequential, we specialise in microbiome analysis and product development for the oral, skin, scalp and vaginal regions, leading the way in solutions that maintain the microbiome. With our expertise, we are well-positioned to collaborate with your company to create innovative products that promote a healthy oral microbiome, enhance microbiota diversity, support lung health, and protect against lung diseases.  References: Cicchinelli, S., Rosa, F., Manca, F., Zanza, C., Ojetti, V., Covino, M., Candelli, M., Gasbarrini, A., Franceschi, F. & Piccioni, A. (2023) The Impact of Smoking on Microbiota: A Narrative Review. Biomedicines. 11 (4), 1144. doi:10.3390/biomedicines11041144. Garmendia, J. & Cebollero-Rivas, P. (2024) Environmental exposures, the oral–lung axis and respiratory health: The airway microbiome goes on stage for the personalized management of human lung function. Microbial Biotechnology. 17 (6), e14506. doi:10.1111/1751-7915.14506. Lin, P., Liu, A., Tsuchiya, Y., Noritake, K., Ohsugi, Y., Toyoshima, K., Tsukahara, Y., Shiba, T., Nitta, H., Aoki, A., Iwata, T. & Katagiri, S. (2023) Association between periodontal disease and chronic obstructive pulmonary disease. The Japanese Dental Science Review. 59, 389–402. doi:10.1016/j.jdsr.2023.10.004. Subbappa, A., Lokesh, K.S., Chaya, S.K., Kaleem Ullah, M., Siddaiah, J.B., Bhojraj, N. & Mahesh, P.A. (2023) Unmasking the Silent Threat: Periodontal Health’s Impact on COPD Severity and Hospitalization. Journal of Personalized Medicine. 13 (12), 1714. doi:10.3390/jpm13121714.

Ginseng, also scientifically known as ​Panax Ginseng, is a medicinal herb that has long been used as a blood-enriching and tonifying agent in Korea, China, and other parts of East Asia. It has various biologically active effects on the human body with minimal side effects. Ginseng improves immunity, blood flow, and memory. It is also found to prevent skin damage from ultraviolet rays, and has antioxidant effects. Recent studies suggest that ginseng may also have a significant impact on the skin microbiome, influencing its composition and function to promote healthier skin. What we know: Ginsenoside is a glycoside that can be extracted from ginseng, and it has been associated with various therapeutic effects, such as reducing wrinkles, improving elasticity, wound-healing, antioxidative, and anti-inflammatory properties (Cong et al ., 2023). Ginseng extract has been shown to support a balanced skin microbiome by promoting the growth of beneficial bacteria and inhibiting harmful pathogens (Hou et al ., 2022). Ginseng has been shown to promote the growth of beneficial bacteria like Staphylococcus epidermidis , which helps maintain skin health by producing antimicrobial peptides and modulating immune responses (Hou et al ., 2022). Ginseng inhibits the growth of pathogenic bacteria such as Staphylococcus aureus , which is known to cause infections and conditions like atopic dermatitis (Hou et al ., 2022). The anti-inflammatory and antioxidant properties of ginseng offer significant benefits for skin health. These properties help in protecting the skin from damage and maintaining a balanced microbiome. Compounds found in ginseng have demonstrated the ability to reduce inflammation and oxidative stress in skin cells (Peng et al ., 2021). Industry impact & potential: Korea Ginseng Corporation (KGC) is a leading producer and global marketer of high-quality Korean red ginseng products, and the company also focuses on research and development to ensure the efficacy and safety of its ginseng products. There is a growing consumer demand for personal care products that promote a healthy skin microbiome. Ginseng's natural properties make it an attractive ingredient for these products, driving innovation and development in the industry. Ginseng's potential to modulate the skin microbiome can be leveraged in developing treatments for skin conditions such as acne, eczema, and psoriasis.  Our solution: Sequential specialises in skin microbiome analysis, and testing formulations in vivo . We also can offer scientifically-backed solutions to enhance skin health through microbiome modulation. We can ensure your product meets industry standards and offers the best skincare quality. Reference: Cong L, Ma J, Zhang Y, Zhou Y, Cong X, Hao M. Effect of anti-skin disorders of  ginsenosides- A Systematic Review. J Ginseng Res. 2023 Sep;47(5):605-614. doi: 10.1016/j.jgr.2023.04.005. Epub 2023 May 4. PMID: 37720567; PMCID: PMC10499590. Hou JH, Shin H, Shin H, Kil Y, Yang DH, Park MK, Lee W, Seong JY, Lee SH, Cho HS, Yuk  SH, Lee KY. Influence of Panax ginseng  formulation on skin microbiota: A randomized, split face comparative clinical study. J Ginseng Res. 2022 Mar;46(2):296-303. doi: 10.1016/j.jgr.2021.12.002. Epub 2021 Dec 14. PMID: 35509819; PMCID: PMC9058842. Peng X, Hao M, Zhao Y, Cai Y, Chen X, Chen H, Zhang Y, Dong L, Liu X, Ding C, Liu W,  Yang M, Luo Y. Red ginseng has stronger anti-aging effects compared to ginseng possibly due to its regulation of oxidative stress and the gut microbiota. Phytomedicine. 2021 Dec;93:153772. doi: 10.1016/j.phymed.2021.153772. Epub 2021 Sep 23. PMID: 34753028.

Perioral dermatitis (PD) is a common and prevalent inflammatory skin condition characterised by small, red papules and pustules around the mouth. While the exact cause of PD remains elusive, research suggests that the skin microbiome could be a significant factor in both the development and treatment of this condition, offering new avenues for understanding and managing PD. What We Know: PD most commonly affects adult women aged 20-45. It can also appear around the eyes (periocular) and nose (paranasal), leading to the alternative name "periorificial dermatitis." Despite this, PD does not share many characteristics with other forms of dermatitis (Tolaymat & Hall, 2024). The exact cause of PD remains unknown, but various environmental factors have been linked to its onset. These include the use of topical and inhaled corticosteroids, which are believed to disrupt the hair follicle microflora and contribute to pathogenesis. Although most patients are female, no hormonal link has been established (Tolaymat & Hall, 2024). PD development is associated with certain oral hygiene practices, such as using fluoride-containing toothpaste, chewing gum and dental fillings. Additionally, excessive skincare routines (e.g., over-exfoliation) and the use of specific cosmetic products (like combining moisturisers and foundations, as well as certain sunscreens) have been implicated (Tolaymat & Hall, 2024). Treatment for PD typically involves topical creams, oral antibiotics and removing cosmetics. Zinc supplementation has also shown efficacy. Avoiding propyl gallate (food additive E310), found in some oils, crisps, spices and cake mixes may also help manage PD, as it is thought to aggravate the condition (Gürtler & Laurenz, 2022). Industry Impact and Potential: Studies suggest that Candida albicans , fusiform bacteria and Demodex  mites may play a role in the onset of PD (Tolaymat & Hall, 2024). Research indicates that Streptococcus  and Rothia  are common on the perioral skin of healthy infants, but more studies are needed to understand the microbial landscape of PD in adults. Given the correlation between PD and epidermal barrier disorders (which are linked to microbial dysbiosis) this area of research holds significant potential for developing new treatments and preventive strategies (Ferček et al., 2021). Our Solution: Exploring the microbial implications of PD could lead to novel treatments like targeted probiotics, prebiotics and microbiome-modulating skincare products. Sequential offers customisable microbiome studies to assess your products' impact on skin microbiome integrity. With our guided formulation services and extensive participant database, we support your efforts to understand and treat conditions like perioral dermatitis, marking an exciting shift towards more effective, personalised dermatology care. References: Ferček, I., Lugović-Mihić, L., Tambić-Andrašević, A., Ćesić, D., Grginić, A.G., Bešlić, I., Mravak-Stipetić, M., Mihatov-Štefanović, I., Buntić, A.-M. & Čivljak, R. (2021) Features of the Skin Microbiota in Common Inflammatory Skin Diseases. Life (Basel, Switzerland). 11 (9), 962. doi:10.3390/life11090962. Gürtler, A. & Laurenz, S. (2022) The impact of clinical nutrition on inflammatory skin diseases. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology: JDDG. 20 (2), 185–202. doi:10.1111/ddg.14683. Tolaymat, L. & Hall, M.R. (2024) Perioral Dermatitis. In: StatPearls. Treasure Island (FL), StatPearls Publishing. p. http://www.ncbi.nlm.nih.gov/books/NBK525968/ .

What we know: Bacterial Vaginosis (BV) affects 23-29% of women worldwide, and it costs $4.8 billion to treat symptomatic BV annually (Peebles et al., 2019) Treatment often only presents temporary relief, with recurrence in around 80% of patients three months of successful treatment (Coudray et al., 2020)  BV is characterised by discomfort of the vagina, it is generally caused by a decrease in amount of Lactobacillus (which we know is dominant in the vaginal microbiomes of healthy women) and an increase in facultative or obligate anaerobic microbes (Chen et al., 2021) (Onderdonk et al., 2016).   Studies have shown that Bacterial Vaginosis prevalence varies between ethnic groups in nearly all of the populations studied In the US bacterial vaginosis has been black race, in the UK Afro-Caribbeans, in Canada aboriginal populations, in Spain Gypsy populations, and in China Tibetan ethnicity all had a higher prevalence - interestingly, all of these groups constitute a minority population in the country researched (Lewis et al., 2017) We know that certain types of hormonal contraceptives can alter the vaginal microbiome, and the use of an oral contraceptive has been found to be consistent with a decrease in BV prevalence (Lewis et al., 2017)  An increased risk of BV is thought to be caused by more frequent vaginal intercourse as well as intercourse with new, multiple, or an increased number of male sexual partners (Lewis et al., 2017)  BV has been associated with a variety of health issues within women, including preterm birth, pelvic inflammatory disease, an increased susceptibility to infection of HIV (Onderdonk et al., 2016) Industry impact & potential: It is clear that a more effective and complex strategy to the treatment and prevention of BV is needed  (According to The National Institute for Health and Care Excellence) Around 50% of BV cases among women are asymptomatic, therefore it is important that reliable technology is developed to better identify BV in an effort to limit misdiagnosis  A pilot study in 2019 highlighted the possibility of using vaginal microbiome transplantation from healthy donors as a treatment for BV, and this presents an interesting potential for the future of treatment. Yet, it has to be noted that the risks and potential long-term consequences need to be studied a great deal more in order to determine whether this has the potential to become a feasible option in the future (Vieira-Baptista et al., 2022) Sequential’s approach: Our Scientific Advisor Professor Phillip Bennett is a key pioneer in vaginal microbiome research. By conducting microbiome testing on intimate care formulations, manufacturers can address common concerns like bacterial vaginosis. Microbiome testing in vaginal care products ensures that they are not only effective in addressing individual concerns, but also gentle and supportive of the natural microbial community. References: Chen X, Lu Y, Chen T, Li R. The Female Vaginal Microbiome in Health and Bacterial Vaginosis. Front Cell Infect Microbiol. 2021 Apr 7;11:631972. doi: 10.3389/fcimb.2021.631972. PMID: 33898328; PMCID: PMC8058480. Coudray MS, Madhivanan P. Bacterial vaginosis-A brief synopsis of the literature. Eur J Obstet Gynecol Reprod Biol. 2020 Feb;245:143-148. doi: 10.1016/j.ejogrb.2019.12.035. Epub 2019 Dec 24. PMID: 31901667; PMCID: PMC6989391. Lewis FMT, Bernstein KT, Aral SO. Vaginal Microbiome and Its Relationship to Behavior, Sexual Health, and Sexually Transmitted Diseases. Obstet Gynecol. 2017 Apr;129(4):643-654. doi: 10.1097/AOG.0000000000001932. PMID: 28277350; PMCID: PMC6743080. Onderdonk AB, Delaney ML, Fichorova RN. The Human Microbiome during Bacterial Vaginosis. Clin Microbiol Rev. 2016 Apr;29(2):223-38. doi: 10.1128/CMR.00075-15. PMID: 26864580; PMCID: PMC4786887. Peebles K, Velloza J, Balkus JE, McClelland RS, Barnabas RV. High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis. Sex Transm Dis. 2019 May;46(5):304-311. doi: 10.1097/OLQ.0000000000000972. PMID: 30624309. Vieira-Baptista P, De Seta F, Verstraelen H, Ventolini G, Lonnee-Hoffmann R, Lev-Sagie A. The Vaginal Microbiome: V. Therapeutic Modalities of Vaginal Microbiome Engineering and Research Challenges. J Low Genit Tract Dis. 2022 Jan 1;26(1):99-104. doi: 10.1097/LGT.0000000000000647. PMID: 34928260; PMCID: PMC8719494.

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

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

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