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Introduction: Cosmetic Preservatives Cosmetics are products designed to enhance or alter the appearance of the face, body, or hair, with effects such as hydration, anti-aging, whitening, and cleansing, depending on their intended purpose. Cosmetic formulations, consist of various ingredients that work together, including, base ingredients (water, surfactants, oils, polymers, emulsifiers) that provide texture and consistency, active ingredients such as hyaluronic acid for hydration or retinol for anti-aging, and colorants (natural or synthetic) that give pigmentation to the product (Tang & Du, 2024). Cosmetics are particularly water-based, and they can create a favorable environment for microbial growth. Therefore, “preservatives” are essential to prevent contamination of microbes and extend shelf life (Tang & Du, 2024). A well-designed preservation system, whether built into the formulation or added externally, should effectively prevent microbial contamination, maintaining product integrity from its sealed state until it is fully used, even after repeated exposure to air and contact (Halla et al ., 2018). Without preservatives, cosmetics could become breeding grounds for harmful bacteria and pose risks of infections or irritations, compromising both safety and effectiveness (Tang & Du, 2024). How do microorganisms contaminate cosmetics? Microbial contamination can occur at various stages, from production to consumer use, making it essential to identify and monitor all potential sources. Contamination during manufacturing (primary contamination) and during consumer handling (secondary contamination) can impact product safety and stability (Figure 1) (Halla et al ., 2018). To prevent microbial contamination in cosmetics, a comprehensive quality management system must be established, covering every stage from raw material selection to final consumer use. This includes strict quality control of raw materials, ensuring that only high-quality, contaminant-free ingredients enter the production process. Hygienic manufacturing processes, including proper cleaning, disinfection, and occupational hygiene, must be strictly followed to minimize the risk of primary contamination during production. Additionally, proper packaging and controlled distribution play a crucial role in preserving product integrity by preventing exposure to environmental contaminants (Uzdrowska & Górska-Ponikowska, 2023). Beyond manufacturing, consumer education on safe usage is equally important, as improper handling, such as using unclean applicators or exposing products to moisture, can introduce secondary contamination (Halla et al ., 2018).  Figure 1: Causes, effects, and prevention of cosmetic contamination. Image taken from   (Halla et al., 2018) . Microorganisms that have been identified in cosmetic products Cosmetic products can provide a favorable environment for microbial growth, particularly when produced under unsanitary conditions. Contamination often involves pathogenic bacteria such as Pseudomonas aeruginosa , Staphylococcus aureus , and Enterobacteria , which pose risks due to their ability to cause infections (Halla et al ., 2018).  Staphylococcus epidermidis  is another commonly detected microorganism linked to skin-related concerns (Alshehrei, 2023). Beyond bacterial contamination, fungal presence is a notable issue, especially Filamentous fungi , which are associated with opportunistic infections and mycotoxin production. Additionally, yeasts like Candida albicans  can proliferate in inadequately preserved formulations, increasing the likelihood of skin and mucosal infections (Halla et al ., 2018).  Although cases of infection from contaminated cosmetics are infrequent, studies have identified recurring microbial contaminants, including Klebsiella oxytoca , Burkholderia cepacia , Escherichia coli , Enterobacter gergoviae , and Serratia marcescens . While intact skin and mucous membranes serve as protective barriers, exposure to these pathogens may elevate infection risks, particularly for individuals with weakened immune systems or compromised skin integrity (Halla et al ., 2018). Regulations that have been placed for cosmetics As the cosmetic industry continues to evolve with the introduction of new ingredients, global regulations have been established to ensure consumer safety, product quality, and accountability for adverse reactions. Among the most influential regulatory frameworks are those from the United States, Japan, and the European Union, as these regions represent the largest cosmetic markets worldwide (Halla et al ., 2018).   United States Regulations In the United States, the Food and Drug Administration (FDA) oversees cosmetic safety and ensures that products entering the market comply with legal requirements. While the FDA does not mandate sterility in cosmetics, products must not contain pathogenic microorganisms, and the total microbial load must remain within safe limits. Although no strict microbial limits are specified by the FDA, the Personal Care Products Council (PCPC) provides industry guidelines, recommending that microbial contamination should not exceed 500 CFU/g for products intended for the eye area or infants and 1,000 CFU/g for all other cosmetics. Additionally, manufacturing facilities are expected to adhere to Good Manufacturing Practices (GMPs) to minimize the risk of microbial contamination (Table 1) (Halla et al ., 2018).       European Union Guidelines   In the European Union (EU), cosmetic safety is regulated under EU Council Directive 76/768/EEC. Microbiological safety guidelines are outlined by the Scientific Committee on Consumer Safety (SCCS), categorizing products into two groups:    Category 1: Products used on mucous membranes, eye area, or intended for children under three years old, where the microbial count must not exceed 100 CFU/g or CFU/mL (Halla et al ., 2018).       Category 2: All other cosmetic products, which must remain below 1,000 CFU/g or CFU/mL (Halla et al ., 2018).       Bacteria such as Pseudomonas aeruginosa , Staphylococcus aureus , and Candida albicans  are considered high-risk contaminants and must be absent in 1 g or 1 mL for Category 1 products and in 0.1 g or 0.1 mL for Category 2 products (Table 1) (Halla et al ., 2018).   Table 1: Regulations that have been placed for cosmetics. These regulations allow for strict quality control, hygiene practices, and microbial safety measures to be maintained in order to reduce contamination risks, ensuring the safety of cosmetic products for consumers. Preservation strategies in cosmetics   Cosmetic manufacturers use various strategies to prevent microbial contamination while maintaining product integrity. Preservation can be chemical, physical, or physicochemical, with two main stages:   1. Primary Preservation  - Implemented during manufacturing, focusing on Good Manufacturing Practices (GMP), including raw material quality control, water treatment, equipment sterilization, and hygienic environments (Halla et al ., 2018).   2. Secondary Preservation  - Applied after production to maintain stability during storage, transport, and consumer use. Different methods are used; Physical Preservation - Protective packaging, such as airless pumps, narrow openings, antimicrobial packaging, can minimise contamination (Halla et al ., 2018).     Physicochemical Preservation - Factors like water activity reduction (using salts, polyols, and hydrocolloids), emulsion type (W/O emulsions offer better protection than O/W), and pH control, that create an unfavorable environment for microbial growth (Halla et al ., 2018).     Chemical Preservation - Includes synthetic preservatives that are regulated under cosmetic laws, natural preservatives such as plant extracts and essential oils, and multifunctional ingredients such as, chelating agents, surfactants, and humectants that enhance microbial resistance while serving additional functions (Halla et al ., 2018).   The combination of these approaches, known as “Hurdle Technology”, ensures cosmetics remain safe, and free from pathogenic microorganisms (Halla et al ., 2018). The preservatives paradox Benefits of preservatives in cosmetics Preservatives play a crucial role in preventing the growth of bacteria, fungi, and other microorganisms, minimizing the risk of infections. Moreover, by maintaining product stability, preservatives help extend shelf life and ensure long-term safety for consumers. Preservatives also allow the development of diverse formulations, particularly those with high water content, which are more prone to microbial contamination (Tang & Du, 2024).  Challenges of preservatives in cosmetics Certain preservatives, such as parabens and isothiazolinones, have been associated with adverse health effects, including skin irritation, and to ensure effective preservation, certain formulas have high concentrations of preservatives, which further increase the risk of toxicity to consumers (Halla et al ., 2018).   Cosmetic preservatives are hazardous micropollutants that often remain in aquatic environments due to incomplete removal in wastewater treatment. These chemicals can harm organisms like fish and algae, raising concerns about their environmental impact (Nowak-Lange, Niedziałkowska & Lisowska 2022). Applying cosmetic products can disrupt the skin microbiota, affecting the balance of the skin, mucous membranes, and scalp. Products like moisturizers, soaps, shampoos, and lotions may alter the skin’s protective lipid layer and impact its natural microflora. This imbalance can result from factors such as preservatives, which remain active after application and interact with microbes, disturbing the bacterial balance (Pinto et al ., 2021). Preservatives impact on the skin microbiome Preservatives can impact the skin microbiome in several ways, and some of which are; Disruption of microbiota Certain preservatives can disrupt the microbiome balance of the skin. A study highlights that skincare products, particularly those with preservatives, influence the skin microbiome. The study found that preservative-free products (PFPs) led to an increase in commensal bacteria such as Sphingomonas   and   Neisseria , which are associated with UV protection, anti-aging effects, and reduced skin inflammation. In contrast, conventional skincare products (CSPs), which typically contain preservatives, showed different microbial shifts and were linked to a less pronounced positive impact on skin microbiome composition.(Wagner et al ., 2024). Disruption of microbial communication Some preservatives may interfere with quorum sensing, which is a way bacteria communicate using signaling molecules to coordinate group behaviors based on population density. Quorum sensing helps regulate functions like enzyme production, biofilm formation, and virulence (Falà et al ., 2022). By disrupting this process, preservatives can inhibit these functions and disrupt the microbial balance.  Alteration of skin pH Certain preservatives can alter the skin's pH, thereby influencing the growth of microorganisms. Maintaining the right pH is crucial for a healthy microbiome, as skincare products directly interact with both skin pH and microbial communities (Janssens-Böcker et al ., 2025).   Barrier function impact Some preservatives such as parabens and formaldehyde releasers, can weaken the skin barrier over time. Exposure to such ingredients may lead to barrier disruption, reducing the skin’s ability to retain moisture, defend against irritants, and maintain homeostasis, potentially causing sensitivity and irritation (Panwar & Rathore, 2024). Comprehensive review: Preservatives & the skin microbiome To gain a deeper understanding of the current knowledge on the impact of preservatives on the skin microbiome, two well-established publications have been selected. Study 1: Effect of commonly used cosmetic preservatives on skin resident microflora dynamics (Pinto et al ., 2021) The study investigated the effects of commonly used cosmetic preservatives (Table 2) on the skin microbiota using  in vitro methods. Methodology Table 2: List of formulations [C1-C12] containing preservatives used in this work. Table taken from (Pinto et al., 2021) . A solution was prepared by combining preservatives at standard concentrations with water and Aristoflex AVC (a gelling agent) to achieve a consistent viscosity. To mimic real skin conditions, a Labskin 3D skin model was utilized, enabling the researchers to observe interactions between the preservatives and the bacterial strains. The bacterial strains studied included Cutibacterium acnes , Staphylococcus epidermidis , and Staphylococcus aureus , which are key skin microbes. These strains were cultured under controlled conditions before being introduced to the 3D skin model.  Following bacterial inoculation, different preservative combinations were applied to the skin models to assess their impact on the skin microbiome. A preservative free gel was used as a control to determine baseline bacterial activity. After 3 hours of contact, two 4mm biopsy samples were collected from each skin model. RNA was extracted from the skin biopsies, and gene expression levels were analyzed using quantitative real-time PCR (qRT-PCR). Results  The results indicate that different preservative combinations have varying effects on skin microbiota (Table 3). Some combinations, such as C2 and C3, strongly inhibit S. aureus while moderately inhibiting C. acnes  without affecting S. epidermidis , making them ideal for restoring microbiome balance. Others, like C1, C4, C6, and C7, moderately inhibited S. aureus  and slightly inhibited C. acnes  while preserving S. epidermidis , suggesting their suitability for maintaining a balanced skin microbiome.   In contrast, combinations like C5, C8, and C9 significantly reduced S. epidermidis , which could disrupt the natural microbiota, making them less ideal for general cosmetic use. Notably, C10 strongly inhibited S. aureus  but had minimal impact on C. acnes  and S. epidermidis , making it a potential choice for targeting S. aureus driven dysbiosis. Table 3: Activity of the different combination of preservatives tested on growth dynamic expressed as % of inhibition. +++, strongly inhibited [< 75%]; ++, moderately inhibited [90–80%]; +, weakly inhibited [98–91%]; −, no inhibition. Table taken from (Pinto et al., 2021) . Conclusion In conclusion, the study shows that different preservative combinations have varying effects on the skin’s microbiome. Hence, choosing the right preservatives in cosmetics is important to keep the skin microbiome healthy and balanced.  There are several limitations of the study. The study only focuses on three bacterial strains Staphylococcus aureus , Staphylococcus epidermidis , and Cutibacterium acnes  which limits its ability to fully represent the diverse and complex skin microbiome. It does not account for the realistic effects of product usage or the dynamic interactions within the skin’s ecosystem. Additionally, the study does not reflect the full functionality of the skin, including its ability to regulate microbial balance. Importantly, it overlooks the microbiome’s natural resilience.  However, the findings provide valuable insights for formulators when having to choose preservatives for cosmetic products. Study 2: In-vivo  impact of common cosmetic preservative systems in full formulation on the skin microbiome (Murphy et al ., 2021) The study investigated the in vivo  impact of common cosmetic preservatives (Table 4) on the skin microbiome. Methodology Table 4: Ingredients of the 4 different formulations. In bold are the preservatives compositions. Table taken from (Murphy et al., 2021) . The study involved 60 healthy adult female participants aged between 18–55 from different ethnicities. 4 products were tested (3 rinse-off and 1 leave-on products), and each product was tested on a group of 15 participants, with no pre-conditioning phase to maintain their natural skin microbiome.  Leg skin microbiome samples were collected from each subject before and after application of the products, and the impact of the preservatives containing products was analyzed by using standard microbiome analysis including taxonomic and diversity analysis. Results: Alpha Diversity Alpha diversity analysis was performed to evaluate the preservatives impact on the  leg skin microbiome before and after product application, by using three common metrics, Chao1, Faith’s Phylogenetic Distance, and Shannon Entropy. All samples were standardized to a read count of 8000 based on rarefaction curve analysis.  Figure 2: Alpha diversity analysis of leg skin microbiome before and after product application. (A) Per sample alpha diversity assessment of the impact of the different preservation systems on the skin microbiome, (B) Group alpha diversity assessment of the impact of the different preservation systems on the skin microbiome, (C) Statistical analysis of alpha diversity changes between timepoints for each preservation system. Image taken from (Murphy et al., 2021) . As shown above (Figures, (A) Alpha diversity per sample for different preservation systems, (B) Group alpha diversity for preservation systems, (C) Statistical analysis of alpha diversity changes over time for each system), no significant changes in alpha diversity were observed after using the products. Results: Beta Diversity Beta diversity analysis was performed to evaluate the potential changes in the microbiome community structure across all product groups. The Bray-Curtis and Jaccard metrics were used to identify any significant shifts in the community after product use (Figures 3A–3D). No significant changes were observed. Fig 3. Beta diversity analysis of leg skin microbiome before and after formulation application. Analysis of the impact of cosmetic products containing different preservation systems (A-D) using Bray Curtis and Jaccard Diversity metrics. Panels A-D correspond to preservation systems A-D. Image taken from (Murphy et al., 2021) . Conclusion The study had several limitations. One being, the product's effectiveness diminishes due to dilution, particularly in wash-off products. Moreover, the study was limited to the leg skin microbiome, and does not apply to other body areas with different microbial compositions. Additionally, the study only focused on short-term effects, leaving the long-term impacts of continuous product use unclear. Finally, not including a preservative-free control group, limited the ability to fully assess the preservatives impact on the skin microbiome. However, despite these limitations the study was able to show us that the preservative containing products had no significant changes in the skin microbiome’s structure or diversity after usage. These data suggest that the different preservation systems in full formulation have minimal impact on the skin microbiome. The analysis also shows that the leg skin microbiome can recover to its original state after using the products. This was true for both wash-off products, which are diluted during use, and leave-on lotions, where the product stays on the skin longer without dilution.  In summary, preservatives are essential for ensuring cosmetic safety and stability, and both the in vitro and in vivo studies highlight the importance of selecting appropriate preservatives, and that when used in full formulation it has only minimal effects on the skin microbiome. However, more future research needs to be done to deepen our understanding of their influence on skin microbiome and health. References Alshehrei F. M. (2023). Isolation and Identification of Microorganisms associated with  high-quality and low-quality cosmetics from different brands in Mecca region -Saudi Arabia. Saudi journal of biological sciences , 30 (12), 103852. https://doi.org/10.1016/j.sjbs.2023.103852 Falà, A. K., Álvarez-Ordóñez, A., Filloux, A., Gahan, C. G. M., & Cotter, P. D. (2022).  Quorum sensing in human gut and food microbiomes: Significance and potential for therapeutic targeting. Frontiers in microbiology , 13 , 1002185. https://doi.org/10.3389/fmicb.2022.1002185 Halla, N., Fernandes, I. P., Heleno, S. A., Costa, P., Boucherit-Otmani, Z., Boucherit, K.,  Rodrigues, A. E., Ferreira, I. C. F. R., & Barreiro, M. F. (2018). Cosmetics Preservation: A Review on Present Strategies. Molecules (Basel, Switzerland) , 23 (7), 1571. https://doi.org/10.3390/molecules23071571 Janssens-Böcker, C., Doberenz, C., Monteiro, M., & de Oliveira Ferreira, M. (2025).  Influence of Cosmetic Skincare Products with pH < 5 on the Skin Microbiome: A Randomized Clinical Evaluation. Dermatology and therapy , 15 (1), 141–159. https://doi.org/10.1007/s13555-024-01321-x Murphy, B., Hoptroff, M., Arnold, D., Eccles, R., & Campbell-Lee, S. (2021). In-vivo impact of  common cosmetic preservative systems in full formulation on the skin microbiome. PloS one , 16 (7), e0254172. https://doi.org/10.1371/journal.pone.0254172 Nowak-Lange, M., Niedziałkowska, K., & Lisowska, K. (2022). Cosmetic Preservatives:  Hazardous Micropollutants in Need of Greater Attention? International Journal of Molecular Sciences , 23 (22), 14495. https://doi.org/10.3390/ijms232214495 Panwar, Aakash & Rathore, Priyanka. (2024). Impact of formulation excipients on skin  barrier functions: A review. International Journal of Pharmaceutical Chemistry and Analysis. 11. 41-44. 10.18231/j.ijpca.2024.005.  Pinto, D., Ciardiello, T., Franzoni, M., Pasini, F., Giuliani, G., & Rinaldi, F. (2021). Effect of  commonly used cosmetic preservatives on skin resident microflora dynamics. Scientific reports , 11 (1), 8695. https://doi.org/10.1038/s41598-021-88072-3 Tang, Zhenyu & Du, Qiaoyan. (2024). Mechanism of Action of Preservatives in Cosmetics.  Journal of Dermatologic Science and Cosmetic Technology. 1. 100054. 10.1016/j.jdsct.2024.100054.  Uzdrowska, Katarzyna & Górska-Ponikowska, Magdalena. (2023). Preservatives in  cosmetics technology. Aesthetic Cosmetology and Medicine. 12. 73-78. 10.52336/acm.2023.008.  Wagner, N., Valeriano, V. D., Diou-Hirtz, S., Björninen, E., Åkerström, U., Engstrand, L.,  Schuppe-Koistinen, I., & Gillbro, J. M. (2024). Microbial Dynamics: Assessing Skincare Regimens’ Impact on the Facial Skin Microbiome and Skin Health Parameters. Microorganisms , 12 (12), 2655. https://doi.org/10.3390/microorganisms12122655

Numerous deodorants and antiperspirant products have been developed to combat and treat malodour or body odour (BO). New approaches target the axillary (underarm) microbiome, the cause of BO, and meadowfoam extract could offer a natural solution. What We Know: Sweat is initially odourless and axillary malodor only develops when the cutaneous microbiome enzymatically breaks down sweat molecules produced by apocrine sweat glands. Certain molecules responsible for the odour associated with sweat have been identified, including an apical efflux pump encoded by the ABCC11  (MRP8) gene (Martin et al., 2010). Bacterium Staphylococcus hominis  has been identified as one bacterium that produces malodorous thiol compounds through the enzymatic degradation of sweat. The enzyme C-S lyase breaks down Cys-Gly-3M3SH, a peptide derivative found in sweat, into constituents including 3M3SH, which is a highly malodorous volatile compound from the thiol family. Due to its thiol nature, 3M3SH has a much lower olfactory threshold than other volatile compounds, making it the primary contributor to the intensity of perspiration odours (Verzeaux et al., 2024). White meadowfoam, Limnanthes alba , is a species of flowering plant native to California and Oregon that is known for its use in cosmetics and hair care products due to its stability, smooth texture and long-lasting presence on the skin (AgMRC, 2023).    Industry Impact and Potential: A deodorant containing meadowfoam extract was shown to be effective in reducing S. hominis. This product significantly reduced  S. hominis  abundance and C-S lyase activity, effectively decreasing odour without disrupting the axillary microbiome balance (Verzeaux et al., 2024). Traditional odour control methods - preventing sweat, masking odours with fragrance, or using antiseptic agents - face criticism due to physiological concerns, potential skin irritation, disruption of the axillary microbiota and the use of controversial ingredients like aluminium salts and alcohol. These issues highlight the need for risk-free, natural solutions that specifically target the biological mechanisms behind malodour production (Verzeaux et al., 2024).   Therefore, researchers propose meadowfoam-containing deodorants as a promising natural alternative for managing BO, with participants reporting high satisfaction in controlling both odour and perspiration (Verzeaux et al., 2024). Our Solution: Sequential is a leading expert in comprehensive, end-to-end microbiome product testing and formulation. Our specialised, customisable services enable businesses to develop innovative products that support and maintain microbiome health, ensuring both effectiveness and compatibility. We offer tailored expertise in facial, oral, scalp and vaginal microbiome research and formulation, providing full support for your product development needs, which may be extended to products targeting the axillary microbiome. References: Martin, A., Saathoff, M., Kuhn, F., Max, H., Terstegen, L. & Natsch, A. (2010) A Functional ABCC11 Allele Is Essential in the Biochemical Formation of Human Axillary Odor. Journal of Investigative Dermatology. 130 (2), 529–540. doi:10.1038/jid.2009.254. Verzeaux, L., Lopez-Ramirez, N., Grimaldi, C., Guedj, O., Aymard, E., Muchico, H. & Closs, B. (2024) Meadowfoam to Control S. Hominis and Axillary Malodor – As Shown by Meta Sequencing and Culturomics. Cosmetics & Toiletries. https://www.cosmeticsandtoiletries.com/cosmetic-ingredients/actives/article/22916729/silab-meadowfoam-to-control-s-hominis-and-axillary-malodor-as-shown-by-meta-sequencing-and-culturomics .

Vaginal seeding involves using a cotton gauze or swab to collect vaginal fluids and transfer them to a newborn's mouth, nose, or skin. This practice is typically done after cesarean deliveries, where the baby doesn’t naturally come into contact with the mother’s vaginal bacteria. The goal of vaginal seeding is to introduce maternal vaginal bacteria to the infant, with the idea that it may promote proper gut colonization and potentially reduce the risk of conditions like asthma, allergies, and immune disorders, which have been linked to rising cesarean delivery rates. What we know: A study found that 30 cesarean-born infants who underwent vaginal seeding had fecal and skin microbiota that more closely resembled those of vaginally born infants during their first year (Kelly, Nolan & Good, 2021). Infant microbiota showed more variability compared to maternal microbiota, with cesarean-born infants having the highest variability, vaginal-born infants the lowest, and vaginally seeded infants displaying intermediate variability in their fecal, oral, and skin samples (Kelly, Nolan & Good, 2021). Research on vaginal microbiota transfer (VMT) through exposure to maternal vaginal fluids revealed that this process significantly accelerated the maturation of gut microbiota in newborns (Zhou et al ., 2023). They also demonstrated that VMT regulated levels of certain fecal metabolites and metabolic functions, including carbohydrate, energy, and amino acid metabolism, within 42 days after birth (Zhou et al ., 2023). VMT also can influence infant neurodevelopment by enhancing various metabolites (Zhou et al ., 2023).   Industry impact & potential: While vaginal seeding shows potential, its long-term effects on health outcomes still needs to be investigated. VMT may influence infant neurodevelopment by enhancing various metabolites; however, the precise mechanisms behind this effect need further investigation for clarification (Zhou et al ., 2023). Our solution: At Sequential, we conduct research on the vaginal microbiome to understand its role in women's health. Our efforts center around leveraging cutting-edge sequencing technologies to thoroughly analyze microbial communities. By characterizing these communities, we aim to identify specific biomarkers that can indicate health conditions or risks. This research not only enhances our understanding of the vaginal microbiome's role in overall well-being but also aids in developing targeted solutions for maintaining vaginal health.  Reference: Committee Opinion No. 725: Vaginal Seeding. Obstet Gynecol. 2017 Nov;130(5):e274-e278.  doi: 10.1097/AOG.0000000000002402. PMID: 29064974. Kelly JC, Nolan LS, Good M. Vaginal seeding after cesarean birth: Can we build a better  infant microbiome? Med. 2021 Aug 13;2(8):889-891. doi: 10.1016/j.medj.2021.07.003. PMID: 35590163. ​​Zhou L, Qiu W, Wang J, Zhao A, Zhou C, Sun T, Xiong Z, Cao P, Shen W, Chen J, Lai X,  Zhao LH, Wu Y, Li M, Qiu F, Yu Y, Xu ZZ, Zhou H, Jia W, Liao Y, Retnakaran R, Krewski D, Wen SW, Clemente JC, Chen T, Xie RH, He Y. Effects of vaginal microbiota transfer on the neurodevelopment and microbiome of cesarean-born infants: A blinded randomized controlled trial. Cell Host Microbe. 2023 Jul 12;31(7):1232-1247.e5. doi: 10.1016/j.chom.2023.05.022. Epub 2023 Jun 15. PMID: 37327780.

Cutaneous T-cell lymphoma (CTCL) is a type of cancer that grow primarily in the skin. The most common forms are Mycosis fungoides (MF) and Sézary syndrome (SS). MF usually appears as red patches, plaques, or tumors on the skin, progressing slowly, while SS is more aggressive, with widespread redness and swollen lymph nodes. CTCL weakens the immune system, leading to frequent infections, chronic inflammation, and reduced ability to fight tumors (Dey et al ., 2024). In Europe and the USA, CTCL affects around 0.55 to 1.06 per 100,000 people, with MF being the most common form (Łyko & Jankowska-Konsur, 2022).  What we know: External factors, such as microbial antigens, may worsen the disease by promoting chronic inflammation and cancerous cell transformation (Dey et al ., 2024). Staphylococcus aureus  and Staphylococcus epidermidis , plays a key role in CTCL (Jost & Wehkamp, 2022). Staphylococcus aureus  contribute to morbidity and mortality by producing enterotoxins that disrupt skin barriers, activate T-cells, and promote cancer progression. In contrast, Staphylococcus epidermidis supports skin barrier function and modulates immune responses through the production of lantibiotics (Jost & Wehkamp, 2022). In CTCL patients, shifts in the abundance of bacteria such as Corynebacterium  and Cutibacterium (Jost & Wehkamp, 2022). Enterococcus  has been found in necrotic tumors of MF patients and successfully treated with antibiotics, while Pseudomonas aeruginosa , often fatal in septic CTCL cases, contributes to over half of the deaths (Jost & Wehkamp, 2022). Staphylococcus aureus  strains were prevalent and showed significant resistance to common antibiotics, complicating treatment with standard therapies (Licht et al ., 2024). Industry impact & potential: 3D human skin culture models could improve our understanding of the interactions between Staphylococcus aureus , immune cells, and malignant cells, while also examining how environmental factors affect skin microbiota, potentially identifying biomarkers or therapeutic targets (Jost & Wehkamp, 2022). Research on the impact of treatment on the skin microbiome in CTCL is still needed, and further studies on non-antibiotic treatments that restore microbiome balance could improve CTCL management (Łyko & Jankowska-Konsur, 2022). Our solution: Sequential specializes in skin microbiome analysis and in vivo formulation testing, providing scientifically-backed solutions to improve skin health through microbiome modulation. We ensure your product meets industry standards and delivers optimal skincare quality. Reference: Dey S, Vieyra-Garcia PA, Joshi AA, Trajanoski S, Wolf P. Modulation of the skin microbiome  in cutaneous T-cell lymphoma delays tumour growth and increases survival in the murine EL4 model. Front Immunol. 2024 Apr 5;15:1255859. doi: 10.3389/fimmu.2024.1255859. PMID: 38646524; PMCID: PMC11026597. Jost M, Wehkamp U. The Skin Microbiome and Influencing Elements in Cutaneous T-Cell  Lymphomas. Cancers (Basel). 2022 Mar 4;14(5):1324. doi: 10.3390/cancers14051324. PMID: 35267632; PMCID: PMC8909499. Licht, P., Dominelli, N., Kleemann, J. et al.  The skin microbiome stratifies patients with  cutaneous T cell lymphoma and determines event-free survival. npj Biofilms Microbiomes 10, 74 (2024). https://doi.org/10.1038/s41522-024-00542-4 Łyko M, Jankowska-Konsur A. The Skin Microbiome in Cutaneous T-Cell Lymphomas  (CTCL)-A Narrative Review. Pathogens. 2022 Aug 18;11(8):935. doi: 10.3390/pathogens11080935. PMID: 36015055; PMCID: PMC9414712.

The menstrual cycle is a recurring process, usually lasting about 28 days. It has four key phases: menstrual, follicular, ovulation, and luteal, each regulated by hormonal changes. These hormonal shifts not only impact reproductive functions but also influence various aspects of a woman's health, including the composition and balance of the vaginal microbiota, which can fluctuate throughout the cycle. What we know: Lactobacillus  species are among the most common colonizers of the vaginal tract in women of reproductive age and are recognized as key components of a healthy vaginal microbiome (Krog et al ., 2022). Lactobacillus  is thought to defend against infections and maintain a healthy vaginal epithelium by producing lactic acid, which lowers the vaginal pH and makes it difficult for pathogenic bacteria to grow (Song et al ., 2020). Menstrual blood neutralizes the acidic vaginal environment, raising the pH, which promotes the growth of anaerobic bacteria like Streptococcus  and Gardnerella , while reducing Lactobacillus  populations, and the iron in menstrual blood also nourishes certain bacteria (Shen et al ., 2022). Women with unstable Vaginal Community Dynamics (VCDs) showed higher phage counts, often dominated by Lactobacillus iners , and had Gardnerella spp  strains more likely to carry bacteriocin-coding genes (Hugerth et al ., 2024). Menstruation triggers an inflammatory response characterized by increased cytokine production and a higher accumulation of mature, activated neutrophils in the vagina, alongside an increase in Streptococcaceae  (Adapen et al ., 2022). Industry impact & potential: Modifying the vaginal microbiota with antibiotics or probiotics could be beneficial , and recognizing effective therapeutic strategies for these modifications is important (Adapen et al ., 2022). Our solution: At Sequential, we have assembled a dedicated team of scientists who have meticulously studied the human microbiome including the vaginal microbiome. With experience collaborating with many clients worldwide, we are well-prepared to partner with your company on intimate female health applications, microbiome testing, in vivo  and clinical certification, and formulation support. Reference: Adapen C, Réot L, Nunez N, Cannou C, Marlin R, Lemaître J, d'Agata L, Gilson E, Ginoux  E, Le Grand R, Nugeyre MT, Menu E. Local Innate Markers and Vaginal Microbiota Composition Are Influenced by Hormonal Cycle Phases. Front Immunol. 2022 Mar 25;13:841723. doi: 10.3389/fimmu.2022.841723. PMID: 35401577; PMCID: PMC8990777. Hugerth, L.W., Krog, M.C., Vomstein, K. et al.  Defining Vaginal Community Dynamics: daily  microbiome transitions, the role of menstruation, bacteriophages, and bacterial genes. Microbiome  12, 153 (2024). https://doi.org/10.1186/s40168-024-01870-5 Krog MC, Hugerth LW, Fransson E, Bashir Z, Nyboe Andersen A, Edfeldt G, Engstrand L,  Schuppe-Koistinen I, Nielsen HS. The healthy female microbiome across body sites: effect of hormonal contraceptives and the menstrual cycle. Hum Reprod. 2022 Jun 30;37(7):1525-1543. doi: 10.1093/humrep/deac094. PMID: 35553675; PMCID: PMC9247429. Shen L, Zhang W, Yuan Y, Zhu W, Shang A. Vaginal microecological characteristics of  women in different physiological and pathological period. Front Cell Infect Microbiol. 2022 Jul 22;12:959793. doi: 10.3389/fcimb.2022.959793. PMID: 35937699; PMCID: PMC9354832. Song SD, Acharya KD, Zhu JE, Deveney CM, Walther-Antonio MRSTetel MJ, Chia N 2020.  Daily Vaginal Microbiota Fluctuations Associated with Natural Hormonal Cycle, Contraceptives, Diet, and Exercise. mSphere5:10.1128/msphere.00593-20. https://doi.org/10.1128/msphere.00593-20

Diabetes mellitus is a recognised risk factor for the development of periodontitis, a gum disease that is characterised by the damage of the soft tissue surrounding the teeth. While the connection between diabetes and oral health is well-documented, targeted research on the oral microbiome in diabetes patients has historically been limited.  What We Know: The interplay between diabetes and periodontitis is bidirectional: poorly managed diabetes results in elevated blood sugar (glucose) levels in oral fluids, promoting the growth of bacteria that can lead to gum disease. Conversely, untreated periodontal infections can raise blood sugar levels, complicating diabetes management (Xiao et al., 2017) . Diabetes also alters the composition of oral bacteria. Studies involving the transfer of oral microbiota from diabetic mice to germ-free mice demonstrate that the microbiota from diabetic mice is more pathogenic. These diabetic mice exhibited increased levels of bacteria such as Proteobacteria (Enterobacteriaceae) and  Firmicutes (Enterococcus, Staphylococcus and  Aerococcus)  which are all associated with periodontitis and impaired healing in diabetic conditions (Xiao et al., 2017) . Industry Impact and Potential: IL-17 is a versatile cytokine involved in both immune defence and pathological immune responses. Elevated levels of IL-17 are observed in chronic periodontitis, where it triggers the production of pro-inflammatory mediators like IL-6 and RANKL, potentially leading to increased osteoclastogenesis, which contributes to bone loss (Xiao et al., 2016) . Research has shown that treatment with IL-17 antibodies can reduce the pathogenicity of the oral microbiome in diabetic mice. When the oral microbiota from IL-17-treated diabetic mice was transferred to germ-free mice, the recipients showed lower levels of neutrophil recruitment, decreased inflammatory markers like IL-6 and RANKL, and reduced bone resorption. This suggests that IL-17 treatment may mitigate the harmful effects associated with the oral microbiota in diabetes (Xiao et al., 2017) . @Frezyderm offers a specially designed oral care range for diabetics, utilising the combination of bioactive peptides and hyaluronic acid in their products. This formulation aims to regulate glucose levels in the mouth, while also reducing bone loss, combating dental plaque, hydrating and healing the gums, as well as preventing cavity formation.  Our Solution: At Sequential, we specialise in microbiome analysis and product development across the oral, skin, scalp and vaginal areas, pioneering innovative solutions that support and preserve the microbiome. With our extensive expertise, we are well-equipped to collaborate with your company in developing products that promote a healthy oral microbiome and overall oral health, for example, protecting against diabetes-associated dysbiosis.  References: Xiao, E., Mattos, M., Vieira, G.H.A., Chen, S., Corrêa, J.D., Wu, Y., Albiero, M.L., Bittinger, K. & Graves, D.T. (2017) Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity. Cell Host & Microbe. 22 (1), 120-128.e4. doi:10.1016/j.chom.2017.06.014. Xiao, W., Li, S., Pacios, S., Wang, Y. & Graves, D.T. (2016) Bone Remodeling Under Pathological Conditions. Frontiers of Oral Biology. 18, 17–27. doi:10.1159/000351896.

Hair and scalp oiling, a traditional Ayurvedic practice with ancient roots, is revered for its holistic health benefits. Today, this ritual is gaining popularity in modern, westernised cosmetic routines, particularly with coconut oil (CO), and emerging research is exploring its potential to influence the scalp microbiome. What We Know: Traditional hair oiling involves applying specific oils, often warmed, to the scalp and hair roots, followed by massage and leaving the oil to penetrate for several hours or days before washing. While CO, derived from Cocos nucifera , is especially popular, other oils like almond, castor, argan, olive, fenugreek, sesame, flaxseed and mustard have also been historically used (Mysore & Arghya, 2022) . The chemical composition of CO includes saturated fatty acids, making it a rich source of medium-chain fatty acids, with major components like myristic acid, capric acid, lauric acid and monolaurin. It also contains phenolic acids and antioxidants, such as tocopherol (Mysore & Arghya, 2022) . CO is prized for its cleansing, protective and restorative properties in haircare. It functions as a saponification agent in shampoos and has antibacterial and antifungal benefits against Cutibacterium acnes  and Staphylococcus aureus  due to its monolaurin content. Acting as an emollient, CO seals the hair cuticle and locks in moisture. Additionally, its low molecular weight and linear chain structure enable it to penetrate the hair shaft, aiding in the prevention of protein loss  (Mysore & Arghya, 2022) . Industry Impact and Potential: A longitudinal study of the scalp microbiome showed that CO may positively influence the scalp microbiome. CO application to the scalp increased beneficial bacteria like C. acnes  and fungi like Malassezia globosa , both of which are linked to healthier scalp conditions and reduced dandruff symptoms. The study also found that CO enriches bacterial pathways related to scalp health, such as biotin metabolism, while decreasing fungal pathogenesis pathway (Saxena et al., 2021) . Various hair care brands have developed scalp oiling products that incorporate CO. However, further research into how products like these may be optimised to benefit the scalp microbiome is largely unexplored and may offer a promising avenue of untapped research and commercial development in the cosmetics industry. Our Solution: With an extensive database comprising over 20,000 microbiome samples and 4,000 ingredients, alongside a global network of more than 10,000 testing participants, Sequential delivers thorough services for assessing product impacts and formulations. Our dedication to creating products that maintain microbiome integrity make us the ideal partner for your scalp and hair care product development needs, including the exploration of oil-based products. References: Mysore, V. & Arghya, A. (2022) Hair Oils: Indigenous Knowledge Revisited. International Journal of Trichology . 14 (3), 84–90. doi:10.4103/ijt.ijt_189_20. Saxena, R., Mittal, P., Clavaud, C., Dhakan, D.B., Roy, N., Breton, L., Misra, N. & Sharma, V.K. (2021) Longitudinal study of the scalp microbiome suggests coconut oil to enrich healthy scalp commensals. Scientific Reports . 11 (1), 7220. doi:10.1038/s41598-021-86454-1.

Skin microbiome transplantation is an emerging therapeutic approach designed to restore a healthy balance of microbial communities on the skin, especially in relation to various dermatological conditions. Recent research has underscored the crucial role of the skin microbiome in maintaining skin health and its contribution to the development of skin diseases like atopic dermatitis, psoriasis, and acne vulgaris. By transplanting healthy skin microbiota, it may be possible to reverse dysbiosis in microbial populations that can trigger inflammatory skin conditions. What we know: Transplantation can involve transferring whole skin microbiota from a healthy individual or using an artificial mixture of selected microorganisms (Junca et al ., 2022). The transplantation method is influenced by the interplay between donor microbiome composition, recipient microbiome composition, and transplant load, with certain combinations enhancing engraftment (Boxberger et al ., 2021). Studies have shown that transferring entire skin microbiomes between different body sites can replicate specific microbial effects, such as odour-causing bacteria could be transferred from the armpit to the forearm (Callewaert et al ., 2021). Transfer of microbiome swabs from the arm to the upper back, found greater diversity in the inner elbow compared to the back. Four arm-specific species persisted on the back after 24 hours, mainly from Gardnerella , Brachybacterium , and Actinomyces  (Callewaert et al ., 2021). In a clinical study, siblings were enrolled, including one with strong body odour. The skin microbiome from the non-odorous sibling was successfully transferred, resulting in reduced body odour and a new microbial balance with more staphylococci  and fewer corynebacteria  (Callewaert et al ., 2021). Industry impact & potential: Transferring live microorganisms from healthy donors to patients poses risks, necessitating pathogen screening standards (Junca et al ., 2022). Standardization of microbiome collection, preparation, and storage methods is essential for assessing transplantation efficacy (Junca et al ., 2022). Understanding microbiome interactions and pathofunctions will support personalized therapeutic strategies targeting specific skin microbiota functions (Junca et al ., 2022). Our solution: Sequential is a company focused on skin microbiome testing, utilizing advanced sequencing technologies to analyze skin microbial communities. We offer valuable insights into the microbiome profiles of individuals skin, enabling the development of personalized treatment plans. By collaborating with dermatologists and researchers, we contribute significantly to the advancement of microbiome-based diagnostics and therapeutics. Reference: Boxberger, M., Cenizo, V., Cassir, N .  Challenges in exploring and manipulating the  human skin microbiome. Microbiome  9, 125 (2021). https://doi.org/10.1186/s40168-021-01062-5 Callewaert C, Knödlseder N, Karoglan A, Güell M, Paetzold B. Skin microbiome  transplantation and manipulation: Current state of the art. Comput Struct Biotechnol J. 2021 Jan 4;19:624-631. doi: 10.1016/j.csbj.2021.01.001. PMID: 33510866; PMCID: PMC7806958. Junca H, Pieper DH, Medina E. The emerging potential of microbiome transplantation on  human health interventions. Comput Struct Biotechnol J. 2022 Jan 19;20:615-627. doi: 10.1016/j.csbj.2022.01.009. PMID: 35140882; PMCID: PMC8801967.

Endometriosis affects around 196 million women worldwide, causing chronic pelvic pain and infertility. This estrogen-dependent condition involves endometrial tissue growing outside the uterus, impacting 6-10% of reproductive-age women. Symptoms include severe cramps, painful intercourse, and pelvic discomfort. Emerging research suggests a link between the urogenital and gastrointestinal systems in its development. (Ser et al ., 2023). What we know: Dysbiosis and infections in the female genital tract can lead to genetic and epigenetic changes that promote oxidative stress and alter immune responses, contributing to the development of endometriosis, with factors like Mycoplasma genitalium  colonization and inflammation influencing gene expression and DNA methylation patterns (Uzuner et al ., 2023). The Estrobolome, involved in estrogen metabolism, impacts endometriosis by altering the vaginal microbiota, with hormonal contraceptives shown to restore normal microbiota and reduce dysbiosis linked to the condition (Zizolfi et al ., 2023). The "bacterial contamination" theory suggests that elevated E. coli  levels in menstrual blood contribute to endometriosis progression by introducing endotoxins that cause inflammation, with increased Proteobacteria   (Uzuner et al ., 2023). Studies reveal distinct changes in the vaginal microbiome of endometriosis patients, with a lower abundance of Lactobacillus  and higher levels of bacteria like Corynebacterium , Enterobacteriaceae , and Streptococcus , especially in advanced stages (Ser et al ., 2023). Endometriosis patients show reduced beneficial gut bacteria Clostridia , Ruminococcus and increased harmful ones Eggerthella lenta , Eubacterium dolicum . The peritoneal microbiome also has elevated Methylobacterium and Streptococcus , suggesting their role in the disease (Ser et al ., 2023). Industry impact & potential: Probiotics like  Lactobacillus gasseri  OLL2809 and multi-strain formulations such as LactoFem® may help manage endometriosis by reducing symptoms and inflammation. However, more research is needed to optimize their use and understand their impact on microbiome stability (Ser et al ., 2023). More research needs to be done on identifying key microbial species linked to endometriosis, exploring their roles in immune activation and microbiota disruption, and understanding the causal relationships between dysbiosis and estrogen metabolism  Our solution: The delicate balance of the vaginal microbiome can be disrupted by the use of inappropriate intimate care products, leading to undesirable conditions. Sequential is committed to uncovering the true effects of formulations on the microbiome in various human conditions, such as Endometriosis. We carry out testing to ensure that vaginal care products are effective in addressing specific concerns while remaining gentle and supportive of the natural microbial community. Reference: Ser HL, Au Yong SJ, Shafiee MN, Mokhtar NM, Ali RAR. Current Updates on the Role of  Microbiome in Endometriosis: A Narrative Review. Microorganisms. 2023 Jan 31;11(2):360. doi: 10.3390/microorganisms11020360. PMID: 36838325; PMCID: PMC9962481. Uzuner C, Mak J, El-Assaad F, Condous G. The bidirectional relationship between  endometriosis and microbiome. Front Endocrinol (Lausanne). 2023 Mar 7;14:1110824. doi: 10.3389/fendo.2023.1110824. PMID: 36960395; PMCID: PMC10028178. Zizolfi B, Foreste V, Gallo A, Martone S, Giampaolino P, Di Spiezio Sardo A. Endometriosis  and dysbiosis: State of art. Front Endocrinol (Lausanne). 2023 Feb 20;14:1140774. doi: 10.3389/fendo.2023.1140774. PMID: 36891056; PMCID: PMC9986482.

Introduction: The gut-brain axis The gut-brain axis is a two-way communication network between the digestive system and the brain, involving hormones, metabolism, the immune system, and other pathways. Key components include the autonomic nervous system, the hypothalamic-pituitary-adrenal (HPA) axis, and gut nerves that link the brain to digestion and immune responses. The gut can also influence mood, cognition, and mental health (Appleton, 2018). Gut bacteria play a crucial role in this relationship, affecting mental health, emotional regulation, and the HPA axis. Changes in the gut microbiome have been linked to mood disorders like anxiety and depression, as well as gastrointestinal (GI) diseases like irritable bowel syndrome, which often coincide with psychological conditions. Gut microbiota also impact brain development in fetuses and newborns, and diet influences how the gut microbiome affects cognitive functions (Appleton, 2018). Depression Depression is a mood disorder characterized by feelings of sadness, emptiness, or irritability, leading to a loss of interest in daily activities. It can cause both mental and physical changes that interfere with everyday life. In the U.S., depression contributes to nearly 40,000 suicides each year, with older men being at the highest risk (Chand & Arif, 2023). Depression can affect anyone, regardless of age or social background, impacting both women and men. If symptoms persist for more than two weeks, it may indicate depression ( InformedHealth.org , 2020). Major Depressive Disorder (MDD) has multiple causes, including biological, genetic, environmental, and psychological factors. While it was initially thought to be due to imbalances in neurotransmitters like serotonin, norepinephrine, and dopamine, newer research suggests disruptions in complex neural circuits. Other neurotransmitters, such as GABA and glutamate, as well as hormonal imbalances, also play a role. Early life stress and trauma can result in lasting brain changes that contribute to depression. Genetics have a strong influence, especially in twins, and life events, personality traits, and cognitive distortions further increase the risk (Chand & Arif, 2023). Diagnosis of major depression is primarily made through a clinical evaluation, including a detailed interview and mental status examination, and is found to be as reliable as many medical tests (Goldman et al., 1999). The DSM-5 provides specific criteria for diagnosing depression (Regier et al., 2013). Treatment typically involves medication and brief psychotherapy, such as cognitive-behavioral therapy (CBT) or interpersonal therapy. Combining these treatments improves symptom relief and quality of life. CBT is particularly effective in preventing relapse. Despite effective treatments, about 50% of people may not initially respond, and full recovery is uncommon. However, around 40% of patients experience partial improvement within a year (Chand & Arif, 2023). Selective Serotonin Reuptake Inhibitors (SSRIs) Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed medications for treating depression. They are usually the first choice for pharmacotherapy because of their safety, effectiveness, and good tolerance in both adults and children (Chu & Wadhwa, 2023).  SSRIs work by increasing the levels of serotonin, also known as 5-hydroxytryptamine (5-HT), in the brain, which is often low in individuals with depression. They do this by blocking the serotonin transporter (SERT) at nerve endings, which prevents the reabsorption (reuptake) of serotonin. This action keeps more serotonin in the brain's synapses, allowing it to have a more prolonged effect on mood (Figure 1). Unlike other antidepressants, SSRIs primarily target serotonin and have minimal impact on other neurotransmitters like dopamine or norepinephrine (Chu & Wadhwa, 2023). Figure 1: A schematic diagram illustrating the mechanism of SSRIs: These medications block the reuptake of serotonin at the presynaptic membrane, leading to increased serotonin levels at the postsynaptic nerve terminal membrane. Image taken from (Lattimore et al., 2005) . Serotonin is also present in the gut mainly at the enterochromaffin (EC) cells of the mucosa. It interacts with various receptors in the gut, the 5-HT3 and 5-HT4 receptors have been most extensively studied for their role in gut motility. It has also been seen that, 5-HT released from EC cells is capable of inducing the mucosal peristaltic reflex and hence propulsive peristalsis (Kendig & Grider, 2015). 5-HT synthesis and gut-brain interaction As mentioned above, serotonin (5-HT) in the gut is produced from tryptophan in enterochromaffin (EC) cells and serotonergic neurons through the actions of tryptophan hydroxylase 1 and 2 (TPH1 and TPH2), converting tryptophan into 5-hydroxytryptophan (5-HTP), which is then turned into serotonin by L-amino acid decarboxylase (L-AADC). This serotonin, along with chromogranin A (CGA), is stored in vesicles via vesicular monoamine transporter 1 (VMAT1). EC cells release serotonin into the extracellular space in response to various stimuli, including chemical and mechanical changes. Most serotonin is released into the extracellular space, with an amount going into the gut lumen. Serotonin is taken up by surrounding enterocytes via the serotonin reuptake transporter (SERT) and then metabolized into 5-hydroxyindoleacetic acid (5-HIAA) by monoamine oxidase (MAO). In serotonergic neurons, serotonin is released into the synaptic cleft, where it acts on postsynaptic receptors and is reabsorbed by SERT. Serotonin is also taken up by endothelial cells and platelets, where it is either converted into 5-HIAA or transported to other tissues (Figure 2) (Liu et al ., 2021). Figure 2: Schematic representation of 5-HT biosynthesis and metabolism. Image taken from (Liu et al., 2021) . The brain-gut hypothesis suggests that serotonin (5-HT) plays a key role in the communication between the gut and the brain. While most serotonin is found in the gut, it also influences brain functions like mood, sleep, and appetite. Imbalances in serotonin levels or receptor activity can result in gastrointestinal issues, such as irritable bowel syndrome (IBS), as well as symptoms in other parts of the body. Research indicates that therapies targeting serotonin can help manage IBS symptoms and related central nervous system dysfunctions (Crowell & Wessinger, 2007). A study investigating the effects of selective serotonin reuptake inhibitors (SSRIs) and the probiotic Lactobacillus rhamnosus  JB-1 on gut-brain signaling through the vagus nerve found some interesting results. Using mouse models, researchers observed that oral SSRI treatment activated vagal pathways, which were crucial for reducing anxiety and depression-like behaviors. Similarly, Lactobacillus rhamnosus  JB-1 alleviated these behaviors, but its effectiveness was reduced in mice with a severed vagus nerve. This highlights the importance of vagal signaling in gut-brain communication. Both SSRIs and the probiotic also affected the gut microbiota and serotonin levels, suggesting the potential of targeting the gut-brain axis in treating mood disorders like anxiety and depression (McVey et al ., 2019). Comprehensive review: Depressive gut microbiota Depressive Gut Microbiota refers to an imbalanced composition and reduced diversity of microorganisms in the gastrointestinal tract, which has been connected to the development and progression of depression.  Studies have shown that individuals with depression exhibit differences in the microbiota community across various taxonomic levels when compared to those without depression, including variations in both α-diversity and β-diversity. At the phylum level, there were inconsistencies in the abundance of Firmicutes , Bacteroidetes , and Proteobacteria , but higher levels of Actinobacteria  and Fusobacteria  were consistently observed in depressed individuals. On the family level, people with depression had increased levels of families like Actinomycineae , Bifidobacteriaceae , Clostridiaceae , and Streptococcaceae , while families such as Veillonellaceae  and Prevotellaceae  were less abundant. At the genus level, those with depression showed higher levels of genera like Oscillibacter , Blautia , Streptococcus , and Klebsiella , with lower levels of beneficial bacteria like Coprococcus , Lactobacillus , and Escherichia/Shigella . These changes in gut microbiota composition are evident in those living with depression, and they are associated with inflammation, gut barrier dysfunction, and disruption of gut-brain communication, contributing to depressive symptoms (Barandouzi et al ., 2020). Study 1: Gut Microbiome Patterns Associated With Treatment Response in Patients With Major Depressive Disorder (Bharwani et al ., 2020) The first long-term study to explore a potential link between major depressive disorder (MDD) and the gut microbiome by analyzing microbial patterns before starting antidepressant treatment and during 6 months of therapy. No other research has looked at the microbiota in individuals who have not yet begun antidepressant use (Bharwani et al ., 2020). Results: Microbial differences Fifteen participants (average age 36.9, SD = 12.9; 12 women) were studied. At the start, their average Montgomery–Åsberg Depression Rating Scale (MADRS) score was 22.53 (SD = 6.63). After 6 months, 11 participants were classified as "remitters" (MADRS < 12) and 4 as "nonremitters" (MADRS > 13). Most participants took Escitalopram, while a few took Citalopram (Bharwani et al ., 2020). Baseline diversity of gut microbiota was higher in remitters than in nonremitters (Figure 3). However, there were no differences in variability or community clustering based on treatment response. At baseline, 22 gut microbiota types of operational taxonomic units (OTUs) were different between the two groups. No significant changes in diversity were observed at 3 months, but differences reappeared at 6 months. Within-subject diversity and community composition showed no significant changes over time for either group (Bharwani et al ., 2020). One OTU, a Clostridiales, increased in remitters at 6 months, while no OTUs changed in nonremitters. At 3 months, 35 OTUs were different between the groups, and by 6 months, 42 OTUs showed differences, with some also differing at 3 months. Diet and antidepressant type had no impact on these results (Bharwani et al ., 2020). Figure 3: Baseline differences between eventual responders and nonresponders in alpha-diversity metrics. Image taken from (Bharwani et al., 2020) . Conclusion The study shows that antidepressant treatment impacts the microbiota at the OTU level, based on how well patients respond to treatment. Although overall diversity and microbiota profiles did not change significantly in either group, remitters continued to have higher diversity compared to nonremitters after 6 months. This indicates a potential microbial community signature that differentiates between treatment responders and nonresponders (Bharwani et al ., 2020). Study 2: Gut Microbial Signatures Can Discriminate Unipolar from Bipolar Depression (Zheng et al ., 2020) Gut microbiome changes are linked to major depressive disorder (MDD) and bipolar disorder (BD), but their specific differences are unclear. This study identifies unique microbial patterns for MDD and BD and offers markers to differentiate between the two based on gut microbiome signatures (Zheng et al ., 2020). Results: Distinct gut microbiome signature in MDD and BD The study compared gut microbiomes across individuals with bipolar disorder (BD), major depressive disorder (MDD), and healthy controls (HC). At the phylum level (Figure 4a), BD had lower Bacteroidetes  and higher Proteobacteria  compared to MDD and HC. At the family level (Figure 4b), BD showed elevated Pseudomonadaceae , while MDD had higher Bacteroidaceae  and Bifidobacteriaceae  but lower Enterobacteriaceae  than HC. Comparing BD and MDD, BD had more Enterobacteriaceae  and Pseudomonadaceae , while MDD showed higher Bacteroidaceae  and Veillonellaceae  (Zheng et al ., 2020). Figure 4: (a) At the phylum level. (b) At the family level. Image taken from (Zheng et al., 2020) . Results: Gut Microbial Biomarkers for Discriminating MDD, BD, and HC  They identified four microbial OTUs, mostly from the  Lachnospiraceae  family, that were strongly linked to Hamilton Depression Rating Scale (HAMD) scores in MDD and BD patients (Figure 5). These microbial markers helped distinguish between MDD, BD, and healthy controls and also indicated the severity of MDD or BD in patients (Zheng et al ., 2020). Figure 5: Four microbial OTUs, primarily from the Lachnospiraceae  family, showed significant links to HAMD scores in MDD and BD patients. Red lines represent positive correlations, while blue lines represent negative correlations, with thicker lines indicating stronger statistical significance (p < 0.05). Image taken from (Zheng et al., 2020) . Conclusion In summary, they identified distinct gut microbiota differences between MDD, BD, and healthy controls. The researchers also found markers that effectively distinguishes MDD from BD and HC.  Looking at all these studies, they confirm that there is a connection between the gut and the brain. Role of the Vagus Nerve The vagus nerve is a key part of the parasympathetic nervous system, responsible for regulating essential functions like mood, immune response, digestion, and heart rate. It serves as a communication link between the brain and the gastrointestinal tract, transmitting information about the condition of internal organs to the brain through afferent fibers (Breit et al ., 2018). Issues with the vagus nerve or changes in its function have been linked to a range of gastrointestinal and psychiatric disorders (Breit et al ., 2018). Importance of Vagus Nerve A study demonstrated that the vagus nerve impacts the anxiety-reducing effects of Lactobacillus rhamnosus  by acting as a conduit for communication between the gut microbiota and the brain. The study shows that when the vagus nerve is severed, the beneficial effects of L. rhamnosus  on anxiety and behavior are lost, indicating that the vagus nerve is essential for transmitting signals from the gut microbiota to the brain. This underscores the nerve’s crucial role in modulating the gut-brain axis, affecting how gut microbiota influence mental health and stress responses (Bravo et al ., 2011). BDNF (Brain-derived neurotrophic factor) BDNF is a protein essential for the growth, maintenance, and survival of neurons in the brain, especially in regions such as the hippocampus, which are critical for memory, learning, and mood regulation. Changes in gut microbiota composition may affect BDNF levels, thereby influencing cognitive functions and neuroplasticity. This underscores the bidirectional relationship between the gut and brain (Agnihotri & Mohajeri, 2022). Lactobacillus in digestive system (Capuco et al., 2020) A study found that patients with major depressive disorder (MDD) who took SSRIs along with the probiotic Lactobacillus plantarum  299v had significantly lower levels of kynurenine, a neurotoxic compound linked to cognitive decline and mood disorders. This group also showed improved cognitive functions, including better attention, perception, and verbal learning, compared to a placebo group. Kynurenine, which can harm the central nervous system, is produced during inflammation triggered by the immune system. The probiotic may have reduced intestinal inflammation, leading to lower kynurenine production and contributing to improved cognition and mood (Capuco et al ., 2020). (Han & Kim, 2019) This study found that isolated Lactobacillus mucosae  NK41 and Bifidobacterium longum  NK46, derived from human feces, increased levels of brain-derived neurotrophic factor (BDNF) in cells stressed with corticosterone. In mice, both probiotics, alone and in combination, reduced anxiety and depression related to stress, lowered inflammation and stress markers in the brain and blood, and improved gut health. They also decreased populations of Proteobacteria  and Bacteroidetes  in the gut, as well as bacterial lipopolysaccharide production. These findings suggest that these probiotics may alleviate anxiety, depression, and colitis by mitigating gut dysbiosis (Han & Kim, 2019). (Yong et al., 2020) Lactobacillus rhamnosus , has shown antidepressant effects in both healthy and stressed mice. Studies in postpartum women and obese individuals also reported reduced depressive thoughts with its use. Its positive effects are linked to signaling through the vagus nerve, influencing brain activity and the stress-regulating hypothalamic-pituitary-adrenal (HPA) axis. L. rhamnosus  produces Gamma-aminobutyric acid (GABA), a neurotransmitter that helps regulate mood, and can cross the gut barrier to interact with neurons. This probiotic also lowers stress hormones and may help prevent depression by boosting GABA levels and protecting against HPA axis overactivity (Yong et al ., 2020). These studies demonstrate that a specific Lactobacillus strain effectively treats major depressive disorder (MDD) by lowering inflammation and increasing serotonin production. Strength and limitations Strengths Clinical Relevance : Understanding the gut-brain axis has key clinical implications for treating various conditions, including mental health disorders like depression, anxiety, and irritable bowel syndrome (IBS), as well as neurological diseases like Parkinson’s and Alzheimer’s. Therapeutic Potential : Research on the gut-brain axis has led to innovative treatments targeting gut microbiota, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), offering potential for managing gastrointestinal and psychiatric disorders. Advanced Technologies : Cutting-edge tools such as metagenomics, metabolomics, and neuroimaging have enhanced the study of the gut-brain axis, helping researchers uncover the mechanisms of gut-brain communication with greater precision. Limitations Correlational Nature : Much of the research is based on associations between gut microbiota and brain function or behavior, making it difficult to establish causality and deeper understanding. Animal Models : Many gut-brain axis studies use animal models, which may not fully reflect human physiology and behavior. Translating these findings to humans requires careful attention to species differences and limitations. Long-term Effects and Safety : The long-term safety and effects of gut microbiota-targeted interventions for mental health are still unclear. More research is needed to evaluate potential risks and benefits over extended periods. Implications and Applications Probiotic Supplements : Recommending probiotics with beneficial bacteria to help balance gut microbiota. Psychotherapy : Using therapies like cognitive-behavioral therapy (CBT) that address both mental health and gut-brain axis interactions. Medication : Considering medications that influence the gut-brain axis, including specific antidepressants or treatments targeting gut microbial imbalances. Education and Awareness : Informing patients about the link between gut health and mental well-being to help them make better lifestyle choices. Related Research and Future Directions Role in Neurological and Psychiatric Disorders : Exploring the influence of the gut-brain axis on a variety of neurological and psychiatric conditions beyond depression and anxiety, such as Alzheimer's, Parkinson's, autism spectrum disorders, schizophrenia, and bipolar disorder. This research could reveal common underlying mechanisms and highlight new therapeutic options. Gut Microbiota and Brain Development : Examining how gut microbiota impacts brain development and function during key stages like infancy, childhood, and adolescence. Insights into early microbial exposures could guide strategies for enhancing neurodevelopment and brain health. Technological Advances : Utilizing cutting-edge tools like microbiome sequencing, multi-omics profiling, neuroimaging, and computational modeling to delve deeper into gut-brain interactions. Combining diverse data sources will allow for more detailed analyses of complex biological systems. Conclusion With the growing pressures of modern life, depression has become increasingly prevalent, yet a complete cure remains unknown. Research on the gut-brain axis suggests a strong connection between depression and changes in the gut microbiota. Depression can disrupt the gut's microbial balance and potentially trigger complications like IBS. IBS, linked to gut microbiota imbalance, also increases the risk of depression. Adjusting and restoring the gut microbiota composition may help alleviate depressive symptoms. This highlights the importance of investigating microbiota-based treatments for depression (Zhu et al ., 2022). References Agnihotri N, Mohajeri MH. Involvement of Intestinal Microbiota in Adult Neurogenesis and  the Expression of Brain-Derived Neurotrophic Factor. Int J Mol Sci. 2022 Dec 14;23(24):15934. doi: 10.3390/ijms232415934. PMID: 36555576; PMCID: PMC9783874. Appleton J. The Gut-Brain Axis: Influence of Microbiota on Mood and Mental Health. Integr  Med (Encinitas). 2018 Aug;17(4):28-32. PMID: 31043907; PMCID: PMC6469458. Barandouzi ZA, Starkweather AR, Henderson WA, Gyamfi A, Cong XS. Altered Composition  of Gut Microbiota in Depression: A Systematic Review. Front Psychiatry. 2020 Jun 10;11:541. doi: 10.3389/fpsyt.2020.00541. PMID: 32587537; PMCID: PMC7299157. Bharwani A, Bala A, Surette M, Bienenstock J, Vigod SN, Taylor VH. Gut Microbiome  Patterns Associated With Treatment Response in Patients With Major Depressive Disorder. Can J Psychiatry. 2020 Apr;65(4):278-280. doi: 10.1177/0706743719900464. Epub 2020 Jan 21. PMID: 31958990; PMCID: PMC7385422. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J,  Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. doi: 10.1073/pnas.1102999108. Epub 2011 Aug 29. PMID: 21876150; PMCID: PMC3179073. Breit S, Kupferberg A, Rogler G, Hasler G. Vagus Nerve as Modulator of the Brain-Gut Axis  in Psychiatric and Inflammatory Disorders. Front Psychiatry. 2018 Mar 13;9:44. doi: 10.3389/fpsyt.2018.00044. PMID: 29593576; PMCID: PMC5859128. Capuco A, Urits I, Hasoon J, Chun R, Gerald B, Wang JK, Kassem H, Ngo AL, Abd-Elsayed  A, Simopoulos T, Kaye AD, Viswanath O. Current Perspectives on Gut Microbiome Dysbiosis and Depression. Adv Ther. 2020 Apr;37(4):1328-1346. doi: 10.1007/s12325-020-01272-7. Epub 2020 Mar 4. PMID: 32130662; PMCID: PMC7140737. Chand SP, Arif H. Depression. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure  Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430847/ Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. [Updated 2023 May 1]. In:  StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554406/ Crowell MD, Wessinger SB. 5-HT and the brain-gut axis: opportunities for pharmacologic  intervention. Expert Opin Investig Drugs. 2007 Jun;16(6):761-5. doi: 10.1517/13543784.16.6.761. PMID: 17501688. Goldman LS, Nielsen NH, Champion HC. Awareness, diagnosis, and treatment of  depression. J Gen Intern Med. 1999 Sep;14(9):569-80. doi: 10.1046/j.1525-1497.1999.03478.x. PMID: 10491249; PMCID: PMC1496741. Han SK, Kim DH. Lactobacillus mucosae  and Bifidobacterium longum  Synergistically  Alleviate Immobilization Stress-Induced Anxiety/Depression in Mice by Suppressing Gut Dysbiosis. J Microbiol Biotechnol. 2019 Sep 28;29(9):1369-1374. doi: 10.4014/jmb.1907.07044. PMID: 31564078. InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in  Health Care (IQWiG); 2006-. Depression: Learn More – Treatments for depression. [Updated 2020 Jun 18]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279282/ Kendig DM, Grider JR. Serotonin and colonic motility. Neurogastroenterol Motil. 2015  Jul;27(7):899-905. doi: 10.1111/nmo.12617. PMID: 26095115; PMCID: PMC4477275. Lattimore, Keri & Donn, Steven & Kaciroti, Niko & Kemper, Alex & Neal, Charles & Vázquez,  Delia. (2005). Selective Serotonin Reuptake Inhibitor (SSRI) Use during Pregnancy and Effects on the Fetus and Newborn: A Meta-Analysis. Journal of perinatology : official journal of the California Perinatal Association. 25. 595-604. 10.1038/sj.jp.7211352.  Liu N, Sun S, Wang P, Sun Y, Hu Q, Wang X. The Mechanism of Secretion and Metabolism  of Gut-Derived 5-Hydroxytryptamine. Int J Mol Sci. 2021 Jul 25;22(15):7931. doi: 10.3390/ijms22157931. PMID: 34360695; PMCID: PMC8347425. McVey Neufeld, KA., Bienenstock, J., Bharwani, A. et al.  Oral selective serotonin reuptake  inhibitors activate vagus nerve dependent gut-brain signalling. Sci Rep  9, 14290 (2019). https://doi.org/10.1038/s41598-019-50807-8 Regier DA, Kuhl EA, Kupfer DJ. The DSM-5: Classification and criteria changes. World  Psychiatry. 2013 Jun;12(2):92-8. doi: 10.1002/wps.20050. PMID: 23737408; PMCID: PMC3683251. Yong SJ, Tong T, Chew J, Lim WL. Antidepressive Mechanisms of Probiotics and Their  Therapeutic Potential. Front Neurosci. 2020 Jan 14;13:1361. doi: 10.3389/fnins.2019.01361. PMID: 32009871; PMCID: PMC6971226. Zheng P, Yang J, Li Y, Wu J, Liang W, Yin B, Tan X, Huang Y, Chai T, Zhang H, Duan J,  Zhou J, Sun Z, Chen X, Marwari S, Lai J, Huang T, Du Y, Zhang P, Perry SW, Wong ML, Licinio J, Hu S, Xie P, Wang G. Gut Microbial Signatures Can Discriminate Unipolar from Bipolar Depression. Adv Sci (Weinh). 2020 Feb 5;7(7):1902862. doi: 10.1002/advs.201902862. PMID: 32274300; PMCID: PMC7140990. Zhu F, Tu H, Chen T. The Microbiota-Gut-Brain Axis in Depression: The Potential  Pathophysiological Mechanisms and Microbiota Combined Antidepression Effect. Nutrients. 2022 May 16;14(10):2081. doi: 10.3390/nu14102081. PMID: 35631224; PMCID: PMC9144102.

In the era of elaborate skincare routines, consumer trends often outpace evidence-based science. Research on popular high frequency (HF) devices, such as the wands commonly used for acne treatment, may offer valuable insights into their true effects on the skin microbiome. What We Know: Developed in the 19th century, HF therapy gained attention for its potential benefits in supporting lymphatic drainage, preventing hair loss and reducing wrinkles. By the early 20th century, it was recognised as a versatile treatment for various conditions, including skin infections, eczema and wounds, as well as ailments like migraines, neuralgia and even tuberculosis (Napp et al., 2015) . HF devices, also known as Violet Wands, function by delivering Cold Atmospheric Pressure Plasma (CAPP) to the site of application, such as the face. This process releases bioactive components, including charged particles and reactive species like ozone and nitrogen oxides (Frommherz et al., 2022). HF therapy ultimately lost popularity in the mid-20th century due to the rise of antibiotics and limited efficacy data. However, with increasing antibiotic resistance, plasma medicine (or CAPP) is gaining renewed interest. Recent studies suggest that HF devices may outperform traditional antiseptics in targeting wound pathogens, raising questions about their potential benefits for acne-prone skin and their impact on the skin microbiome (Daeschlein et al., 2015) . Industry Impact and Potential: Recent research has demonstrated that HF therapy possesses a microbicidal effect on skin microbiota and pathogens in vitro , significantly reducing bacterial and fungal counts after just a brief treatment. Notably, one minute of HF application led to a significant reduction in C. acnes levels (Frommherz et al., 2022) . It is hypothesised that HF therapy increases ozone formation during application, suggesting that its primary antimicrobial effects stem from ozone and the oxidative stress it induces in microbes. Ozone is also recognised for its anti-inflammatory properties, further enhancing its efficacy in treating skin conditions (Frommherz et al., 2022) . Ultimately, the antiseptic properties of HF therapy present a promising alternative to antibiotics for managing conditions like acne ( Frommherz et al., 2022) . However, it is important to remember that not all HF devices available, especially cheaper options, are created equal; variations in voltage, frequency and design can affect their efficacy and safety.  Our Solution: With a database of 25,000 microbiome samples and 4,000 ingredients, plus a global network of testing participants, Sequential provides customised solutions for microbiome studies and product formulation. Our commitment to developing microbiome-safe products ensures the preservation of biome integrity, making us an ideal partner investigating the skin, scalp, oral and vaginal microbiome. References: Daeschlein, G., Napp, M., von Podewils, S., Scholz, S., Arnold, A., Emmert, S., Haase, H., Napp, J., Spitzmueller, R., Gümbel, D. & Jünger, M. (2015) Antimicrobial Efficacy of a Historical High-Frequency Plasma Apparatus in Comparison With 2 Modern, Cold Atmospheric Pressure Plasma Devices. Surgical Innovation . 22 (4), 394–400. doi:10.1177/1553350615573584. Frommherz, L., Reinholz, M., Gürtler, A., Stadler, P.-C., Kaemmerer, T., French, L. & Clanner-Engelshofen, B.M. (2022) High-frequency devices effect in vitro: promissing approach in the treatment of acne vulgaris? Anais Brasileiros de Dermatologia . 97, 729–734. doi:10.1016/j.abd.2021.09.015. Napp, J., Daeschlein, G., Napp, M., von Podewils, S., Gümbel, D., Spitzmueller, R., Fornaciari, P., Hinz, P. & Jünger, M. (2015) On the history of plasma treatment and comparison of microbiostatic efficacy of a historical high-frequency plasma device with two modern devices. GMS hygiene and infection control . 10. doi:10.3205/dgkh000251.

Recent research into aroma perception - the process by which the brain detects scent molecules from food - has primarily focused on the physical and chemical properties of these substances and their release during chewing. However, the role of the oral microbiome in this process is still underexplored, offering new insights into how microorganisms shape the flavours we experience. What We Know: While taste is detected by the tongue’s taste buds, aroma involves volatile compounds released from food that are detected by olfactory receptors in the nose. Aroma significantly enhances flavour, allowing us to distinguish foods with similar tastes. During chewing, aroma compounds travel from the mouth to the nasal cavity (retronasal olfaction), blending with taste to create a complete sensory experience (Xi et al., 2024) . The oral microbiome plays a crucial role in aroma perception. These microorganisms interact with food compounds in various ways, such as breaking down odourless molecules and transforming them into volatile compounds that we perceive as aroma. Moreover, the oral microbiota influences how taste and smell signals are processed by the brain, further affecting overall flavour perception (Xi et al., 2024) . Emerging research indicates that oral microbiota help metabolise complex food precursors, such as glycosides, into flavour-active molecules during chewing. A balanced oral microbiome enhances flavour perception, while an imbalance may dull or alter this sensory experience (Xi et al., 2024) . Industry Impact and Potential: Research is still in infancy regarding the role of the oral microbiome in aroma perception. Therefore, harnessing the power of oral bacteria to enhance flavours or create novel sensory experiences is a promising avenue of exploration. Furthermore, understanding how the oral microbiome contributes to the perception of scent and taste could also lead to the development of targeted oral care products that maintain or improve flavour perception by supporting a healthy microbiome. A company that harnesses the intricate relationship between taste, scent, and retronasal olfaction is @air up®, which has developed innovative water bottles featuring built-in scent-releasing pods. This design allows users to enjoy unflavoured water while experiencing specific flavours, as the released scents interact with the olfactory system to create a taste sensation in the mouth. Our Solution: Sequential is a leading authority in microbiome product testing and formulation, offering customisable solutions that empower businesses to innovate oral hygiene products while preserving microbiome integrity. We ensure the efficacy and compatibility of products for a healthier oral microbiome, making us the ideal partner to help your company explore the potential of oral, as well as skin, scalp and vaginal, microbiome studies and product development.  References: Xi, Y., Yu, M., Li, X., Zeng, X. & Li, J. (2024) The coming future: The role of the oral–microbiota–brain axis in aroma release and perception. Comprehensive Reviews in Food Science and Food Safety . 23 (2), e13303. doi:10.1111/1541-4337.13303.