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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. 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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.

Bacterial vaginosis (BV) affects over half of women globally at some point in their lives, primarily due to a Lactobacillus -deficient vaginal microbiome. Despite this knowledge, there have been no significant advancements in effective BV treatments for nearly four decades, making this a critical area of research and interest. What We Know: BV is characterised by an imbalance in the vaginal microbiome, marked by a low abundance of beneficial Lactobacilli  and an overgrowth of diverse anaerobic bacteria. This imbalance leads to clinical symptoms such as discharge, odour and mucosal inflammation. BV is also linked to several adverse health outcomes, including preterm birth, infertility, cervical dysplasia and increased susceptibility to sexually transmitted infections (STIs), including HIV (Zhu et al., 2024) . Standard antibiotic treatments, like metronidazole (MTZ), often fail to provide lasting relief, with over 50% of patients experiencing recurrence within a year. This is partly because antibiotics tend to favour the growth of Lactobacillus iners  over Lactobacillus crispatus , the latter being associated with better health outcomes (Zhu et al., 2024) . Industry Impact and Potential: Recent research has shown that oleic acid (OA) and similar unsaturated long-chain fatty acids (uLCFAs) can inhibit L. iners  while simultaneously promoting the growth of L. crispatus.  These uLCFAs are essential for cell membranes and possess antimicrobial properties that suppress harmful microbes. Remarkably, OA has been found to encourage L. crispatus  dominance more effectively than traditional antibiotics in laboratory models of BV, suggesting a promising metabolite-based treatment approach (Zhu et al., 2024). Specific genes in non-iners Lactobacillus  species allow them to thrive in OA-rich environments. The gene farE  is crucial for OA resistance, while the enzyme ohyA helps these bacteria utilise OA for building their cell membranes. Importantly, treatments for BV that include OA - alone or in combination with metronidazole (MTZ) - enhance the growth of beneficial  L. crispatus  in lab studies. This research highlights different nutrient utilisation strategies among Lactobacillus  species and points to new approaches for improving women’s reproductive health (Zhu et al., 2024). Our Solution: At Sequential, we are at the forefront of microbiome research and development, offering comprehensive services beyond vaginal microbiome analysis. We also evaluate skin, scalp and oral microbiomes, establishing our leadership in testing products that maintain microbiome integrity. Our team of specialists excels in helping your company develop robust studies tailored to enhance the vaginal microbiome, promoting women's health and well-being. References: Zhu, M., Frank, M.W., Radka, C.D., Jeanfavre, S., Xu, J., et al. (2024) Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment. Cell . 187 (19), 5413-5430.e29. doi:10.1016/j.cell.2024.07.029.

Microplastics, the small plastic debris that result from the breakdown of consumer products and industrial waste, are widely recognised for their harmful environmental effects. However, little research has explored how these particles - which are found in up to 70% of cosmetic products - affect the skin microbiome. What We Know: Microplastics are tiny, solid plastic particles composed of polymers and additives. They are typically less than 5 mm and can be unintentionally formed through the wear and tear of larger plastic items (@European Chemicals Agency, 2024). These particles, including microbeads and fibres, are commonly found in personal care products like shower gels, toothpaste and nail polish and include polyethylene, polyethylene terephthalate and polypropylene. Microplastics serve various roles, from exfoliating beads in scrubs to enhancing product texture and stability, and even as glitter in makeup (Mim et al., 2024; Bashir et al., 2021). In Europe, it’s estimated that around 3800 tonnes of microplastics are released into the environment annually through everyday cosmetic and personal care products (@European Chemicals Agency, 2024). Microplastics can adsorb organic and inorganic contaminants on their surfaces, where biofilms may form, potentially acting as carriers of pathogenic vectors, pollutants, antimicrobial resistance, microorganisms and resistance genes. This raises concerns about how these particles may interact with the skin microbiome when present in cosmetic products (Mim et al., 2024).  Additionally, nanoplastics - smaller than microplastics, typically around 100 nm or less - can potentially penetrate biological barriers and may have toxic effects when present in topical products (Yong, Valiyaveettil & Tang, 2020). Industry Impact and Potential: Research on the impact of microplastics on the gut microbiome has shown that these particles can lead to significant shifts, including increased α-diversity and higher levels of potentially harmful pathobionts. As a result, it is widely hypothesised that microplastics may also be detrimental to the skin microbiome. However, further research is essential to elucidate the mechanisms behind these effects (Mim et al., 2024).  @Beat the Microbead is an innovative app developed by the @Plastic Soup Foundation that enables users to scan cosmetic product barcodes to check for microplastics. This empowers consumers to take control of their microplastic exposure and make informed choices, even before regulations and legislation fully address the issue. Our Solution: Sequential is a global leader in microbiome product development and testing, with locations in London, New York and Singapore. Our expertise and customisable services allow businesses to innovate confidently, ensuring their products preserve microbiome integrity and meet specific goals, such as efficacy, compatibility and environmental sustainability. References: Bashir, S.M., Kimiko, S., Mak, C.-W., Fang, J.K.-H. & Gonçalves, D. (2021) Personal Care and Cosmetic Products as a Potential Source of Environmental Contamination by Microplastics in a Densely Populated Asian City. Frontiers in Marine Science. 8. doi:10.3389/fmars.2021.683482. Mim, M.F., Sikder, M.H., Chowdhury, M.Z.H., Bhuiyan, A.-U.-A., Zinan, N. & Islam, S.M.N. (2024) The dynamic relationship between skin microbiomes and personal care products: A comprehensive review. Heliyon. 10 (14). doi:10.1016/j.heliyon.2024.e34549. Yong, C.Q.Y., Valiyaveettil, S. & Tang, B.L. (2020) Toxicity of Microplastics and Nanoplastics in Mammalian Systems. International Journal of Environmental Research and Public Health. 17 (5), 1509. doi:10.3390/ijerph17051509.

Every person’s skin is unique, shaped by genetics, the environment and lifestyle factors. Research demonstrates that personalised skincare, particularly when tailored to the skin microbiome, delivers more effective and lasting results by addressing each individual’s specific needs, promoting healthier and more resilient skin. What We Know: Human skin varies significantly due to genetic differences, which influence how it responds to environmental stressors, its susceptibility to ageing and its reactions to skincare products. These genetic variations are closely linked to factors like skin pigmentation, structure and sensitivity to UV radiation (Markiewicz & Idowu, 2018). Personalised skincare addresses these individual differences by tailoring products and treatments to each person's unique needs. This approach is gaining popularity in the cosmetics industry as it offers more effective and targeted solutions than generic skincare products. The primary benefits of personalised skincare include improved efficacy, as products are customised to match individual skin characteristics, and enhanced protection against environmental damage and ageing. By catering to the specific needs of different skin types, personalised skincare can also more effectively prevent or mitigate skin conditions (Markiewicz & Idowu, 2018). Industry Impact and Potential: A study that investigated the use of microbiome-tailored skincare products found that these products significantly enhanced skin health by supporting a more diverse and balanced skin microbiome. In the study, participants used microbiome-supporting (MS) products on one cheek and benchmark (BM) products on the other for three weeks. The results showed that the MS products led to a notable increase in beneficial bacterial diversity, reduced skin redness and improved skin texture. In contrast, the BM products only provided minor improvements in skin texture and did not significantly impact other skin health parameters (Santamaria et al., 2023). Parallel Health  uses whole genome sequencing to analyze an individual’s skin microbiome, creating customized phage-based skincare solutions. These serums target harmful bacteria causing issues like acne and rosacea while supporting beneficial microbes. The process includes a microbiome test, personalized consultations, ongoing skin assessments, and tailored serums for continuous skin health. Our Solution: Sequential's personalised skincare approach harnesses the power of microbiome-based facial products through its comprehensive Microbiome Product Testing Solution. This end-to-end service supports both independent testing and expert-guided formulation, enabling businesses to develop innovative, tailored skincare solutions that cater to individual microbiomes. References: Markiewicz, E. & Idowu, O.C. (2018) Personalized skincare: from molecular basis to clinical and commercial applications. Clinical, Cosmetic and Investigational Dermatology. 11, 161–171. doi:10.2147/CCID.S163799. Santamaria, E., Åkerström, U., Berger-Picard, N., Lataste, S. & Gillbro, J.M. (2023) Randomized comparative double-blind study assessing the difference between topically applied microbiome supporting skincare versus conventional skincare on the facial microbiome in correlation to biophysical skin parameters. International Journal of Cosmetic Science. 45 (1), 83–94. doi:10.1111/ics.12826.

Collagen is widely celebrated in the skincare industry for its anti-ageing and rejuvenating benefits. Recent research reveals that marine collagen peptides, used both orally and topically, support wound healing and may enhance skin health by modulating the skin microbiome. What we know: Collagen, the most abundant protein in the human body, comprises 30% of total protein content. Oral hydrolysed collagen boosts collagen peptides in the bloodstream, improving skin elasticity, hydration, and reducing water loss. Topically, it moisturizes the stratum corneum, reduces dryness and wrinkles, and enhances skin elasticity ( Gabriel Aguirre Alvarez  et al., 2020).  Skin wounds pose a major socio-economic challenge in healthcare. Treatments include collagen alginate dressings, silver sulfadiazine cream, autografts, allografts, and xenografts. Acellular fish skin (AFS) grafts have recently gained attention as a cost-effective option, acting as a 'skin substitute' that reduces inflammation and promotes pro-healing cytokines to improve wound recovery ( Hanna Luze  et al., 2022). The expression of nucleotide-binding oligomerization domain containing 2 (NOD2) and β-defensin (BD14) at the wound site directly affect the types of microorganisms that colonise wound (Mei et al., 2020). Industry impact and potential: A new xenograft technique utilising AFS grafts from Atlantic cod or Nile tilapia fish has shown promising results in wound healing. These grafts have demonstrated significant anti-inflammatory and antibacterial properties, which enhance the healing process for various types of wounds, including burns and DFUs. Current research is focused on comparing the effectiveness of fish skin grafts with other wound healing methods (Ibrahim et al., 2023). Research shows that oral collagen peptides from Atlantic salmon and Nile tilapia skin accelerate wound healing by upregulating NOD2 and BD14, key to immune response and skin repair. These peptides enhance collagen deposition, angiogenesis, and promote beneficial microbes like Leuconostoc and Enterococcus while suppressing harmful ones like Stenotrophomonas and Sphingomonas, improving overall wound healing outcomes (Mei et al., 2020). Products such as  ELEMIS  ‘Pro-Collagen Marine Cream’ and  Naturallythinking  ‘Marine Collagen Facial Cream’ are examples of topical approaches to utilising these beneficial collagen peptides. Further research into the benefits of topical and oral marine collagen for skin health, beyond wound healing, presents an exciting opportunity—especially in exploring its impact on the skin microbiome.  Our solution: Sequential provides a unique end-to-end microbiome product testing solution, complemented by specialised product development and formulation services. Leveraging our expertise, we assist businesses in creating innovative skin products, such as collagen-containing wound healing solutions, that preserve microbiome integrity and promote overall skin health. References: Aguirre-Cruz, G., León-López, A., Cruz-Gómez, V., Jiménez-Alvarado, R. & Aguirre-Álvarez, G. (2020) Collagen Hydrolysates for Skin Protection: Oral Administration and Topical Formulation. Antioxidants (Basel, Switzerland). 9 (2), 181. doi:10.3390/antiox9020181. Ibrahim, M., Ayyoubi, H.S., Alkhairi, L.A., Tabbaa, H., Elkins, I. & Narvel, R. (2023) Fish Skin Grafts Versus Alternative Wound Dressings in Wound Care: A Systematic Review of the Literature. Cureus. 15 (3), e36348. doi:10.7759/cureus.36348. Luze, H., Nischwitz, S.P., Smolle, C., Zrim, R. & Kamolz, L.-P. (2022) The Use of Acellular Fish Skin Grafts in Burn Wound Management-A Systematic Review. Medicina (Kaunas, Lithuania). 58 (7), 912. doi:10.3390/medicina58070912. Mei, F., Liu, J., Wu, J., Duan, Z., Chen, M., Meng, K., Chen, S., Shen, X., Xia, G. & Zhao, M. (2020) Collagen Peptides Isolated from Salmo salar and Tilapia nilotica Skin Accelerate Wound Healing by Altering Cutaneous Microbiome Colonization via Upregulated NOD2 and BD14. Journal of Agricultural and Food Chemistry. 68 (6), 1621–1633. doi:10.1021/acs.jafc.9b08002.

Scalp malodour is a significant concern, and unlike other body areas associated with unpleasant odour, there are currently no specific cosmetic or hygiene products designed to address it. Emerging research is shedding light on the role of the scalp microbiome in this issue, revealing how we can manipulate it to find effective solutions. What We Know: Body odour carries a strong social stigma around it and its psychological impact is not fully understood. Nevertheless, this olfactory cue is hypothesised to play a role in kinship detection and mate selection within human communities (Lam et al., 2018). Human body odour arises from bacterial decomposition of odourless sweat constituents like fatty acids and amino acids from eccrine, apocrine, and sebaceous glands. While Corynebacterium  species are linked to malodour at various body sites, research on the microbial causes of scalp malodour remains limited (James et al., 2013). Industry Impact and Potential: A study on body odour in prepubescent children and teenagers found that the mid-scalp region emits a distinct greasy odour, unlike the neck and underarms, which have a ‘sour+sulphur’ smell that shifts to primarily ‘sulphur’ after exercise. The mid-scalp consistently exhibits a dominant ‘sour’ odour, suggesting unique microbial metabolism in this area (Lam et al., 2018). Research suggests that the microbiome of the scalp is more stable compared to those of other areas of the body. This stability is attributed to the limited impact of showers on the scalp's microbial community and the presence of microbes residing in the hair follicles, which contribute to a more resilient and stable microbiome (Lam et al., 2018). A study found higher levels of Malassezia globosa  and  Cutibacterium acnes  in the scalp and neck compared to the underarms, with children’s scalps dominated by M. globosa  and teenagers’ by C. acnes , aligning with apocrine gland changes during puberty. However, no specific microbes were identified as linked to scalp malodour (Lam et al., 2018).  An additional study demonstrated that diacetyl (2,3-butanedione) is a major contributor to malodour of the scalp (Hara, Matsui & Shimizu, 2014). To truly unlock the potential of microbiome science in tackling scalp malodour, further research is essential. This exploration could revolutionise our approach to hair care, paving the way for innovative products that not only address but transform our understanding of scalp health.  Our Solution: With a database of 20,000 microbiome samples and 4,000 ingredients, along with a global network of 10,000 testing participants, Sequential offers customised solutions for microbiome studies and product formulation. 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 malodour-addressing scalp care solutions. References: Hara, T., Matsui, H. & Shimizu, H. (2014) Suppression of Microbial Metabolic Pathways Inhibits the Generation of the Human Body Odor Component Diacetyl by Staphylococcus spp. PLOS ONE. 9 (11), e111833. doi:10.1371/journal.pone.0111833. James, A.G., Austin, C.J., Cox, D.S., Taylor, D. & Calvert, R. (2013) Microbiological and biochemical origins of human axillary odour. FEMS Microbiology Ecology. 83 (3), 527–540. doi:10.1111/1574-6941.12054. Lam, T.H., Verzotto, D., Brahma, P., Ng, A.H.Q., Hu, P., Schnell, D., Tiesman, J., Kong, R., Ton, T.M.U., Li, J., Ong, M., Lu, Y., Swaile, D., Liu, P., Liu, J. & Nagarajan, N. (2018) Understanding the microbial basis of body odor in pre-pubescent children and teenagers. Microbiome. 6 (1), 213. doi:10.1186/s40168-018-0588-z.

Introduction The human skin is constantly exposed to various environmental factors, with ultraviolet radiation (UVR) being a major influence on skin health and disease. UVR is divided into UVA, UVB, and UVC. Sunlight primarily consists of UVA (90–95%) and a smaller portion of UVB (5–10%), while UVC is almost entirely absorbed by the ozone layer and does not reach the Earth's surface (Rai, Rai & Kumar, 2022). Both UVB and UVA can lead to DNA damage, oxidative stress, premature aging, and an increased risk of skin cancer. Additionally, UVR has been linked to immune suppression and may significantly affect the skin’s microbiome. Hence, photoprotective measures are important to consider in order to protect the skin against the harmful effects of UVR (Grant, Kohil & Mohammad, 2024). Is UVR good or bad? UVR has several positive effects, including the activation of anti-inflammatory and immunosuppressive pathways, which benefit various skin conditions like psoriasis, atopic dermatitis, vitiligo, graft-versus-host disease, and can influence certain infections as UVR promotes vitamin D production, which may help reduce the risk of respiratory tract infections and tuberculosis (TB), with higher solar UVB exposure linked to lower TB incidence. UVR also enhances immune responses, such as macrophage activity and antimicrobial peptide production, which aid in combating infections (Hart et al ., 2019).  Beyond skin diseases, UVR also plays a beneficial role in systemic conditions such as asthma, multiple sclerosis, schizophrenia, type 1 diabetes, autism, and cardiovascular diseases. These effects result from interactions between UVR-induced regulatory cells and mediators like nitric oxide, interleukin-10, and 1,25-dihydroxy vitamin D3 (Rai, Rai & Kumar, 2022). Moderate exposure to UV radiation is also beneficial for health and plays a crucial role in the production of vitamin D (Xiaoyou et al ., 2024). Prolonged UVR exposure can generate reactive oxygen species (ROS) both directly by affecting cellular components and indirectly through photosensitization mechanisms. Indirectly produced ROS include various species such as superoxide anions (O2.-), singlet oxygen, hydroxyl radicals, and hydrogen peroxide, formed through different pathways. These free radicals can be further converted into other ROS types. Low ROS levels can cause mutations, medium levels may induce cellular senescence, and high levels typically lead to cell death, including apoptosis and necrosis (Figure 1) (Xiaoyou et al ., 2024). UVR damages DNA as well through two main mechanisms: direct and indirect. Direct damage, primarily from UVB rays, leads to the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts, which distort the DNA structure. Indirectly, UVA radiation generates reactive oxygen species (ROS) that oxidize DNA bases, causing mutations like 8-oxoguanine  (Figure 1) (Xiaoyou et al ., 2024). Both types of damage can impair DNA repair, leading to mutations, skin aging, and an increased risk of skin cancers.  Figure 1: UVR triggers the production of reactive oxygen species (ROS) and causes DNA damage. Chromophores absorb UV light, generating ROS such as superoxide anions (O2.-), singlet oxygen, hydroxyl radicals, and hydrogen peroxide through various pathways. UV-induced DNA damage primarily results in the formation of cyclobutane-pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PP), typically at dimerization sites. ROS can also contribute to single-strand breaks (SSBs) and double-strand breaks (DSBs) in DNA. Image taken from (Xiaoyou et al., 2024) . UV radiation (UVR) affects different age groups in distinct ways. Children generally face a lower risk of UV-related skin damage compared to adults. However, certain UV-induced conditions, such as photoaging (early skin wrinkling), freckles, and moles, can manifest during childhood and adolescence. Severe UV damage in early life may also increase the risk of long-term complications, including benign and malignant skin tumors, such as melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), later in adulthood (Green, Wallingford & McBride, 2011). In Japanese populations, the first sign of photoaging typically appears as solar lentigines on the face around the age of 20. This is followed by the development of fine wrinkles after 30, and benign skin tumors, like seborrhoeic keratoses, commonly appearing on sun-exposed skin after 35 (Ichihashi & Ando, 2014).  The response to UVR also varies with age at the cellular level. Younger skin has more efficient DNA repair mechanisms, while aging skin experiences increased DNA damage and impaired repair capacity due to the presence of senescent fibroblasts and reduced production of insulin-like growth factor-1 (IGF-1) (Kemp, Spandau & Travers, 2017). While UVR is essential for our health by aiding in vitamin D production and providing therapeutic benefits, excessive exposure poses serious risks. To enjoy the advantages of UVR while reducing its harmful effects, it’s crucial to implement preventive and protective measures. A key aspect of this understanding lies in recognizing the relationship between UV radiation and the skin microbiome. Skin Microbiome The human skin hosts a diverse array of bacteria, fungi, and viruses that form its microbiota. These microbes are crucial for maintaining skin homeostasis by protecting against pathogens, stimulating the immune system, and breaking down natural host products. Microbial populations are organized into complex communities that significantly influence the functionality of healthy skin. When the microbiota is disrupted, it can adversely affect the skin's immune homeostasis and contribute to systemic diseases (Willmott et al ., 2023). The skin primarily hosts four main bacterial phyla; Actinobacteria , Firmicutes , Proteobacteria , and Bacteroidetes . In moist regions, Staphylococcus  and Corynebacterium are the most prevalent. Oily areas tend to exhibit less diversity, with Cutibacterium  being the dominant species. In contrast, dry areas of the skin show the greatest diversity, consisting of a wide range of these four phyla (Smyth & Wilkinson, 2023). What is the relationship between UV and the Skin Microbiome As a unique ecosystem, human skin and its microbial inhabitants are also influenced by external environmental stressors, including UVR (Burns et al ., 2019). UVR can directly or indirectly affect the skin microbiome. Studies have shown changes in the composition of the skin microbiome, with different bacteria responding differently to UVA and UVB radiation (Gilaberte et al ., 2024). A study published in 2023 found significant changes in microbial beta diversity after four weeks of extensive sunlight exposure on the forearms of participants, compared to baseline measurements. Prior to taking a holiday in a sunny destination (minimum of 7 days duration), volunteers had skin swabs taken from their extensor forearm (d0), and upon their return, skin swabs were repeated at d1, d28, and d84. This suggests that sun exposure influences the diversity and composition of the skin microbiota (Willmott et al ., 2023). Additionally, the overall composition of the skin microbiome may be altered long-term following exposure to UVA and UVB radiation on the backs of the volunteers. Notable increases were observed in Cyanobacteria spp. , Fusobacteria spp. , Verrucomicrobia spp. , and Oxalobacteraceae spp.  In contrast, Lactobacillaceae spp.  and Pseudomonadaceae spp. decreased, with a more pronounced decline following UVA exposure (Burns et al ., 2019).  Research indicates that, similar to skin cells, bacteria respond differently to the UVA and UVB components of UVR. One study examining the effects of UVR on Pseudomonas aeruginosa  found that both UVA and UVB contribute to bacterial inactivation, shedding light on the vulnerability of specific microorganisms to UVR. Another study compared the responses of P. aeruginosa  to those of Escherichia coli  under similar conditions. While UVA significantly impacted the viability of P. aeruginosa , it had little to no observable effect on E. coli  (Smith et al ., 2023). UVR, Skin Microbiome, and Immune System Interaction The effects of UVR on the skin microbiome can occur through both direct and indirect mechanisms. UVR presents an immediate threat to both mammalian and microbial cells. Additionally, UVR can alter the microbial habitat of exposed skin, leading to further changes in the skin microbiome. One indirect mechanism involves the increased expression of antimicrobial peptides (AMPs) by the skin in response to UVR. Some species within the skin microbiome exhibit resistance to UVR, such as  Micrococcus luteus , which utilizes carotenoid pigments and has high endonuclease activity to counteract the otherwise bactericidal effects of UVR (Smith et al ., 2023). At sub-toxic levels, UVR can trigger a pathogen/damage-associated molecular pattern (PAMP/DAMP) response. This response may result in the release of microbial signals like oleic acid, lipopolysaccharides (LPS), and porphyrins, which can alter immune signaling and promote inflammation (Patra, Byrne & Wolf, 2016). Microbial metabolites can influence dendritic cells, aiding in the recognition and capture of pathogens. Additionally, microorganisms can produce natural antimicrobial peptides (AMPs) or regulate their production in keratinocytes, with UVR exposure potentially enhancing AMP levels. The UVR-induced cis-UCA may not only lead to an altered immune response but could also indirectly modify the microbial load by affecting the skin's microenvironment through unknown mechanisms. Furthermore, the microbiome can induce complement and interleukin-1 (IL-1) in response to UVR stress, influencing skin immunity through various cytokines, particularly in the Th17 pathway. Consequently, the production of IL-17 by keratinocytes may lead to changes in AMP production, creating a loop that ultimately affects the microbiome (Figure 2) (Patra, Byrne & Wolf, 2016). UVR can weaken the body's immune response to infectious microorganisms, potentially increasing the risk of microbial infections or elevating existing ones. This occurs as UVR induces dysbiosis, disrupting the natural balance of the skin microbiome and altering skin homeostasis. When the protective microbial community is compromised, harmful pathogens may thrive, leading to higher susceptibility to infections. Additionally, the changes in immune signaling pathways caused by UVR can impair the skin's ability to defend against these pathogens, further heightening the risk of skin-related infections and inflammatory conditions. Understanding this interplay emphasizes the importance of protecting the skin from excessive UV exposure to maintain both skin health and overall immune function (Gilaberte et al ., 2024). Figure 2:  Possible mechanisms microbes can influence UV-induced immune suppression. Image taken from (Patra, Byrne & Wolf, 2016) . Some fungi display photomorphogenic effects when exposed to UV light. A study found that increased doses of UV radiation reduced the production of porphyrins by Cutibacterium acnes , showing that these facial bacteria respond to UV exposure. They noted that C. acnes  reacted to UV-B at doses lower than 20 mJ/cm², even before any significant skin damage occurred (Wang et al ., 2012). Malassezia spp. , part of the normal skin flora, can cause pityriasis versicolor, a common skin condition mainly in tropical areas. At the typical sites of this condition, sunburn is rarely triggered. Malassezia furfur produces a UV-filtering compound known as pityriacitrin, which is believed to offer protective benefits. However, UVR is also known to suppress the cellular growth of  Malassezia furfur (Patra, Byrne & Wolf, 2016). Sunscreen, UV, and Skin Microbiome In recent years, effective sun protection strategies have been developed, emphasizing personalized approaches like wearing sun-protective clothing and using sunscreen. Modern sun protection products feature photostable, broad-spectrum UVA/UVB filters to protect against sunburn, skin cancer, photodermatoses, and photoaging. Many also include active ingredients that help prevent hyperpigmentation and premature skin aging, extending protection beyond just UV radiation (Schuetz et al ., 2024). There have been recent questions about how sunscreen affects the skin microbiome, though limited research is available. Nanoparticles like coated titanium dioxide (TiO₂) and zinc oxide (ZnO) in sunscreens have been shown to have antimicrobial effects, due to their ability to release metal ions and generate reactive oxygen species (ROS). The impact of these nanoparticles varies depending on the microorganism. Coated TiO₂ does not significantly affect skin bacteria growth, while UV exposure increases the bactericidal activity of uncoated ZnO. Most sunscreens use coated ZnO and TiO₂ particles, which are less harmful to bacteria (Grant et al ., 2024).  Factors like particle size, pH, preservatives, and added antimicrobial compounds in sunscreens may also influence the skin microbiome. Organic UV filters have been found to inhibit the growth of marine bacteria, fungi, and fish gut microbiota, but their direct effect on human skin bacteria is less known (Grant et al ., 2024). Study: Sunscreens can preserve human skin microbiome upon erythemal UV exposure (Schuetz et al ., 2024) In the above study they compared the effect of sunscreen SPF20 and placebo on UV exposed skin. Erythema was prominently observed in the unprotected areas, partially in the placebo treated zones, but was absent in the SPF20 treated areas, indicating effective photoprotection from the SPF (Schuetz et al ., 2024). The In vitro  results found that L. crispatus  was one of the most affected microbes when sunscreen was applied, showing a positive association with its abundance. In contrast, Cutibacterium acnes  did not show significant changes in its relative abundance. UV exposure reduced the ratio of  Lactobacillus  to Cutibacterium , indicating more Cutibacterium in those areas, while the sunscreen helped restore the original balance between these two types of bacteria (Schuetz et al ., 2024). L. crispatus  is common in the skin microbiome of younger individuals (18-35 yrs) and is also prevalent in the vaginal microbiome, playing an important role in women's health (Garlet et al ., 2024) (Schuetz et al ., 2024) (Argentini et al ., 2022).  Certain microorganisms, like L. crispatus , benefit from extra UV protection, as mentioned in the above clinical study. To confirm these results, they developed an in vitro model using individual bacteria and UV filters. They tested the survival of Lactobacillus crispatus , Cutibacterium acnes , and Staphylococcus epidermidis  under UV stress (Schuetz et al ., 2024). The results showed that specific UV filters, such as octocrylene and zinc oxide, improved the survival of L. crispatus  compared to the control. Combinations of these filters also protected L. crispatus , similar to the in vivo findings. However, some filters, like butyl methoxydibenzoylmethane, reduced the population of C. acnes , while maintaining or increasing S. epidermidis  levels. This suggests that choosing the right UV filters in sunscreens is very important (Figure 3) (Schuetz et al ., 2024). In conclusion, the above study provided valuable insights into the protective effects of an SPF 20 sunscreen on the skin microbiome after UV exposure. The findings highlight the relationship between UV radiation and the skin microbiome, emphasizing the importance of sun protection for maintaining healthy skin (Schuetz et al ., 2024). In the test, various UV filter formulations showed different effects on microbial survival. For example, some filters improved the survival of Lactobacillus crispatus , while others reduced Cutibacterium acnes  (Schuetz et al ., 2024). Despite limitations due to the small number of volunteers and sample variability, there results suggest that applying sunscreen before UV exposure can be beneficial for the skin microbiome. The researchers also believe that sunscreens with higher SPF values may offer even greater protection (Schuetz et al ., 2024). Lactobacillus crispatus , may help protect the skin and support its immune response, similar to its role in vaginal health. The ability of select UV filters to preserve beneficial bacteria while reducing harmful C. acnes  could lead to new skincare products aimed at protecting both skin and its microbiome from UV stress, enhancing overall skin resilience (Schuetz et al ., 2024). Figure 3: The survival rates of each microbial population four hours after exposure were calculated as a percentage compared to the initial population, with the relative protection provided by the UV filters expressed as a percentage. Image taken from (Schuetz et al., 2024) . Probiotics for Protecting Your Skin Microbiome from UV Damage  Probiotics are live microorganisms that provide health benefits to the host when consumed in sufficient amounts. Certain strains of lactic acid bacteria have been found to positively influence gut microbiota composition and metabolism, and in some cases, they can inhibit the growth of harmful bacteria. Research has shown a link between the gut-immune axis and skin health, with probiotic-rich foods helping to maintain skin balance and support the immune system (Souak et al ., 2021). Probiotics have also shown potential in protecting against UV-induced skin damage. For example, Lactobacillus johnsonii  NCC 533 (La1) has been found to help stabilize the skin's immune system by preventing UV-induced increases in interleukin-10 and reducing the recruitment of Langerhans cells. Similarly, Lactobacillus rhamnosus  GG (LGG) has been shown to prevent UV-related skin tumors due to its lipoteichoic acid (LTA), a component of gram-positive bacteria cell walls (Souak et al ., 2021).  Other potential probiotic candidates for photoprotection include Lactobacillus plantarum HY7714, Bifidobacterium breve , and Bifidobacterium longum  (Souak et al ., 2021). Conclusion In conclusion, protecting both the skin and its microbiome can help lower the risk of imbalances caused by UVR. Using sunscreens not only provides effective sun protection but also strengthens the skin barrier, which may help preserve a healthy microbiome by minimizing the penetration of harmful UV rays and environmental stress (Gilaberte et al ., 2024). More studies need to be done to understand how different wavelengths of UVR affect the skin microbiome, as well as the long-term impact of UVR on skin health, including its role in chronic conditions and aging. Additionally, further research is needed to explore how sunscreens influence the microbiome and more high-quality clinical studies are essential to confirm the potential of these approaches in safeguarding the skin microbiome from the effects of solar radiation (Gilaberte et al ., 2024). References Argentini C, Fontana F, Alessandri G, Lugli GA, Mancabelli L, Ossiprandi MC, van Sinderen  D, Ventura M, Milani C, Turroni F. Evaluation of Modulatory Activities of Lactobacillus crispatus Strains in the Context of the Vaginal Microbiota. Microbiol Spectr. 2022 Apr 27;10(2):e0273321. doi: 10.1128/spectrum.02733-21. Epub 2022 Mar 10. PMID: 35266820; PMCID: PMC9045136. 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Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition characterized by recurrent, painful nodules and abscesses. It mainly affects areas of the body with skin folds, including the armpits, groin, and beneath the breasts. The impact of the condition goes beyond physical discomfort, such as associated pain, drainage, malodor, and scarring often result in significant negative psychosocial effects for those affected. Studies have revealed notable changes in the skin microbiome of individuals with HS, indicating a complex interaction between microbial communities and the disease's pathophysiology. What we know: HS patients exhibit an altered skin microbiome compared to healthy individuals. This dysbiosis is characterized by a reduction in microbial diversity and an overrepresentation of certain pathogenic bacteria (Lelonek et al ., 2023). Studies have found differences in specific bacterial taxa between HS patients and the control group. For instance, it was found that Mesorhizobium ,  Porphyromonas  and Peptoniphilus were more abundant in HS skin than healthy skin, and that Cutibacterium spp.  were decreased in HS patients (Lelonek et al ., 2023). An increased level of Gram-negative Porphyromonadaceae , Prevotellaceae , Fusobacteria , and Clostridales  in HS patients have also been noted​ (Luck et al ., 2022). The microbiota in various body sites of HS patients are less diverse and more similar to each other than in healthy individuals (Schneider et al ., 2020). In a study an increase in Finegoldia magna  in the groin and axilla of HS patients but a decrease in nasal swabs of these patients were observed (McCarthy et al ., 2022). Industry impact & potential: Non-obese HS patients have a different microbiome composition from obese ones, with subtle changes. More research is needed to understand these differences and their effects on the disease (Lelonek et al ., 2023). Microbiome research in HS could lead to new diagnostic tools and treatments. For example, profiling the microbiome might help identify those at risk for severe HS or predict how they will respond to treatments. Our solution: Sequential is a company specializing in skin microbiome testing, and we use advanced sequencing technologies to analyze skin microbial communities. We provide valuable insights into the microbiome profiles of individuals with HS or any skin conditions, helping to tailor personalized treatment. By partnering with dermatologists and researchers, we play a pivotal role in advancing microbiome-based diagnostics and therapeutics. Reference: Lelonek E, Bouazzi D, Jemec GBE, Szepietowski JC. Skin and Gut Microbiome in  Hidradenitis Suppurativa: A Systematic Review. Biomedicines. 2023 Aug 16;11(8):2277. doi: 10.3390/biomedicines11082277. PMID: 37626773; PMCID: PMC10452269. Luck ME, Tao J, Lake EP. The Skin and Gut Microbiome in Hidradenitis Suppurativa: Current  Understanding and Future Considerations for Research and Treatment. Am J Clin Dermatol. 2022 Nov;23(6):841-852. doi: 10.1007/s40257-022-00724-w. Epub 2022 Sep 18. PMID: 36116091. McCarthy S, Barrett M, Kirthi S, Pellanda P, Vlckova K, Tobin AM, Murphy M, Shanahan F,  O'Toole PW. Altered Skin and Gut Microbiome in Hidradenitis Suppurativa. J Invest Dermatol. 2022 Feb;142(2):459-468.e15. doi: 10.1016/j.jid.2021.05.036. Epub 2021 Aug 6. PMID: 34364884. Schneider AM, Cook LC, Zhan X, Banerjee K, Cong Z, Imamura-Kawasawa Y, Gettle SL,  Longenecker AL, Kirby JS, Nelson AM. Loss of Skin Microbial Diversity and Alteration of Bacterial Metabolic Function in Hidradenitis Suppurativa. J Invest Dermatol. 2020 Mar;140(3):716-720. doi: 10.1016/j.jid.2019.06.151. Epub 2019 Aug 27. PMID: 31465743.