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Silver is widely recognised for its antimicrobial properties, but its precise effects on the skin microbiome remain an emerging area of research. Recent studies suggest that silver could offer both opportunities and challenges in treating skin-related conditions. What We Know: Silver is commonly incorporated into products such as gels, dressings and textiles in forms like nanoparticles, silver oxynitrate and colloidal silver (Silva, Teixeira & Reis, 2023). Silver nanoparticles exhibit strong antibacterial activity, particularly against Staphylococcus epidermidis  and Staphylococcus aureus  - key skin microbiome components that can form biofilms. These biofilms make bacterial infections harder to treat and more resistant to antibiotics, positioning silver as a promising alternative (Swolana & Wojtyczka, 2022). The antimicrobial mechanism of silver nanoparticles involves disrupting bacterial cell membranes, generating reactive oxygen species (ROS) and interfering with bacterial DNA and proteins. Their effectiveness depends on factors like particle size, shape and concentration (Swolana & Wojtyczka, 2022). Additionally, silver-based gels show increased antimicrobial action with higher concentrations. They are particularly effective against Gram-negative bacteria and have the potential to alter microbial composition while maintaining physicochemical stability, making them viable options for skin infection treatments (Silva, Teixeira & Reis, 2023). Industry Impact and Potential: Recent research into silver-threaded clothing revealed that while silver increased microbial diversity and enriched certain low-abundance bacterial taxa, it did not reduce overall microbial biomass. Instead, it altered the skin’s chemical profile, notably increasing monounsaturated fatty acids (MUFAs) and driving site- and gender-specific changes in the microbial composition (Melnik et al., 2023). This indicates silver’s potential to modulate the skin microbiome in targeted ways. However, questions remain about its long-term effects, particularly its impact on microbiome stability and beneficial microbes. Future research could optimise concentrations and delivery mechanisms to maximize therapeutic benefits while minimizing unintended consequences (Melnik et al., 2023). While silver’s antimicrobial properties are promising, its broader effects on skin health require deeper investigation​ (Swolana & Wojtyczka, 2022). Our Solution: Sequential is leading the way in microbiome research, leveraging a database of 20,000 microbiome samples, 4,000 ingredients and a global network of 10,000 testing participants. Our customisable solutions span microbiome studies and product formulation, with a strong emphasis on preserving biome integrity. Whether exploring the skin, scalp, oral or vulvar microbiome, we are your trusted partner in advancing science and innovation. References: Melnik, A.V., Callewaert, C., Dorrestein, K., Broadhead, R., Minich, J.J., Ernst, M., Humphrey, G., Ackermann, G., Gathercole, R., Aksenov, A.A., Knight, R. & Dorrestein, P.C. (2023) The Molecular Effect of Wearing Silver-Threaded Clothing on the Human Skin. mSystems. 8 (1), e0092222. doi:10.1128/msystems.00922-22. Silva, J.M., Teixeira, A.B. & Reis, A.C. (2023) Silver-based gels for oral and skin infections: antimicrobial effect and physicochemical stability. Future Microbiology. 18, 985–996. doi:10.2217/fmb-2023-0034. Swolana, D. & Wojtyczka, R.D. (2022) Activity of Silver Nanoparticles against Staphylococcus spp. International Journal of Molecular Sciences. 23 (8), 4298. doi:10.3390/ijms23084298.

An imbalanced oral microbiome is a key contributor to the development of dental caries, periodontitis, and halitosis. Probiotics offer promising solutions to help restore microbial equilibrium and support sustained oral health. What We Know: Research increasingly shows that oral diseases are influenced not only by individual pathogens or opportunistic bacteria, but by the overall structure and function of the microbial community. It is therefore essential to study the oral microbiome as an integrated ecosystem rather than focusing solely on single species (Yu et al., 2024). Several species have been investigated for their probiotic potential in oral care, including Lactobacillus plantarum  and Weissella cibaria . A recent review on L. plantarum  highlights its capacity to suppress opportunistic species such as Streptococcus mutans  and Candida albicans , as well as reduce oral inflammation. These properties suggest its potential use in caries and periodontitis prevention (Huang et al., 2024). Clinical studies of W. cibaria  have demonstrated reductions in volatile sulfur compounds (VSCs), improved halitosis scores, and better gingival health. One trial observed changes in microbiota composition and a reduction in bleeding on probing following 8 weeks of supplementation (Han et al., 2023). These probiotics appear to act through a combination of mechanisms: competitive exclusion of opportunistic species, production of antimicrobial compounds like bacteriocins, modulation of pH, and immune system interactions. Common delivery formats include lozenges, chewable tablets, mouth rinses, and functional chewing gums—formulations that promote direct contact with oral surfaces and support colonisation (Kang et al., 2020).   Industry Impact and Potential:   While short-term benefits of oral probiotics are well supported, long-term colonisation and sustained effects remain a key focus. Studies show that microbiome changes can reverse once probiotic intake stops, highlighting the need for well-designed longitudinal studies to assess durability and safety over time (Yu et al., 2024).   Our Solution:   Sequential provides a comprehensive end-to-end Microbiome Product Testing Solution coupled with expert guidance in product development and formulation. Drawing on our extensive expertise, we collaborate with businesses to pioneer innovative strategies for creating topical treatments that, for example, may harness the power of probiotics.   References: Huang, X., Bao, J., Yang, M., Li, Y., Liu, Y., & Zhai, Y. (2024). The role of Lactobacillus plantarum  in oral health: a review of current studies. Journal of Oral Microbiology , 16 (1). https://doi.org/10.1080/20002297.2024.2411815 Han HS, Yum H, Cho YD, Kim S. Improvement of halitosis by probiotic bacterium Weissella cibaria  CMU: A randomized controlled trial. Front Microbiol. 2023 Jan 17;14:1108762. doi: 10.3389/fmicb.2023.1108762. PMID: 36733919; PMCID: PMC9886871. Kang, MS., Lee, DS., Lee, SA. et al.  Effects of probiotic bacterium Weissella cibaria  CMU on periodontal health and microbiota: a randomised, double-blind, placebo-controlled trial. BMC Oral Health  20, 243 (2020). https://doi.org/10.1186/s12903-020-01231-2 Yu X, Devine DA, Vernon JJ. Manipulating the diseased oral microbiome: the power of probiotics and prebiotics. J Oral Microbiol. 2024 Jan 31;16(1):2307416. doi: 10.1080/20002297.2024.2307416. PMID: 38304119; PMCID: PMC10833113.

Introduction Hyperpigmentation is a common and usually harmless dermatological condition characterised by patches of skin that are darker than the surrounding skin. It can occur as a result of excessive production of the pigment melanin by skin cells, and appears in various forms ranging from melasma to age spots (solar lentigines), or post-inflammatory hyperpigmentation (Plensdorf, Livieratos and Dada, 2017). Melanin-over production and hyperpigmentation has been linked to a range of diverse triggers, including but not limited to, skin injury or inflammation, sun damage, hormonal changes, and pregnancy. Some medicines such as birth control pills and hormone replacement (British Skin Foundation) might also induce hyperpigmentation as a side-effect (National Cancer Institute, 2025).  Certain skin types are more likely to be affected by different types of hyperpigmentation based on physiology and response to risk factors, with lighter skin (Fitzpatrick types I to III) more prone to age spots or ephelides (freckles) (Plensdorf, Livieratos and Dada, 2017), and melasma or post-inflammatory hyperpigmentation occurring more frequently in darker skinned populations (Fitzpatrick types IV to VI) (Lawrence, Syed and Al Aboud, 2025). The role of the skin microbiome in regulating the development of hyperpigmentation conditions is an emerging area of interest in medical dermatology. The skin microbiome is a specialised community of microorganisms (bacteria, fungi, viruses, and more) that live and grow on the skin, where they play an essential role in multiple processes that maintain skin health like preventing growth of pathogens, priming the immune system (Lunjani et al. , 2021), and regulating skin growth and development (Meisel et al. , 2018). Environmental and host-associated factors that affect microbial community structure have been found to correlate with the onset of hyperpigmentation in some cases.  For example, the growth of certain groups of bacteria, such as Corynebacteria , has been found to positively correlate with the emergence of hyperpigmented spots (Dimitriu et al. , 2019). Furthermore, Staphylococcus, Cutibacterium, and Lactobacillus  abundance on the skin might have some protective properties against photoaging and skin injury following UV exposure (Li et al. , 2020). However, very few studies have been conducted looking into the direct relationship between the skin microbiome and hyperpigmentation, with several knowledge gaps remaining surrounding the contribution of resident microbes to maintaining skin homeostasis and emergence of hyperpigmented spots. Understanding this relationship will be key to facilitating the development of skin microbiome-based therapeutics for the treatment of these conditions. Study No. 1: Bacterial taxa predictive of hyperpigmented skins (Zanchetta et al. , 2022) This clinical study, conducted on 38 European women grouped by facial hyperpigmentation level, aimed to directly characterise the role of the skin microbiota in the emergence of hyperpigmented spots (HPS) by identifying bacterial populations present on skin with dark spots (Zanchetta et al. , 2022). Results: Alpha‐diversity between high HPS and low HPS skin types were found to be similar. However, the significant differences were identified for minor taxa such as Bergeyella, Micrococcus, Paracoccus, Kocuria, Alloiococcus, and Exiguobacterium , which were present in significantly higher proportions in the low HPS skin group, while in the high HPS group Eikenella, Xanthomonas, Brevibacterium, Aerococcus, Turicella, Paucibacter , and Klebsiella were more abundant. Further analysis revealed the bacteria Kocuria and Aerococcus  as being the two taxa best at predicting the HPS level of the skin.  Kocuria  are capable of producing the thiazolyl peptide kocurin, which inhibits the growth of some Staphylococcus aureus  strains associated with chronic skin inflammation and infection, two triggers for the emergence of brown spots. Furthermore, the genus Micrococcus  was found to be present in significantly higher proportions on skins with less HPS (0.95%) compared to those with more HPS (0.21%), where it might play a role in promoting antioxidant and UV-protective properties. Cross‐domain association networks to characterise bacterial interactions associated with different levels of HPS found relationships between dominant skin residents Cutibacterium and Staphylococcus , and Peptoniphilus and Finegoldia  in the group with a low level of HPS. Skin with a higher HPS level instead showed a disappearance of this connection between Cutibacterium and Staphylococcus , while other more fragmented networks emerged like between Streptococcus and Veillonella , or those involving other minor taxa. The overall stability of these associations was higher on skin with a low HPS level (Zanchetta et al. , 2022). Conclusions: These results reveal specific microbiota composition and networks on skins based on level of skin hyperpigmentation, with changes to this capable of possibly altering overall skin physiology, immune regulation and emergence of HPS. They also present an opportunity for the development of cosmetic therapies for hyperpigmentation that target the skin microbiome and its dynamic interactions for skincare applications (Zanchetta et al. , 2022). Study No. 2: Clinical effect of Pediococcus acidilactici PMC48 on hyperpigmented skin (Park et al. , 2024) This clinical study sought to investigate the potential role of the melanin-decomposing probiotic strain Pediococcus acidilactici  PMC48 in skin medicine and cosmetics by looking at its whitening effect when topically applied to artificially UV-induced tanned skin in a cohort of 22 Korean participants (Park et al., 2024). Results: Topical application of PMC48 to UV‑induced hyperpigmented skin led to several significant improvements in physical skin parameters compared to the control group, with a 47.65% reduction in colour intensity, an 8.10% increase in skin brightness, and an 11.82% drop in melanin index reported, demonstrating PMC48’s tyrosinase (an enzyme involved in the melanin-production pathway) inhibition, and melanin degrading capabilities. Skin moisture content of pigmented sites after PMC48 application were also found to improve by 20.94%. Analysis of the microbiomes of the participants revealed skin treated with PMC48 experienced an increase in Lactobacillaceae abundance by up to 11.2% without disturbing other microbial populations or affecting overall community diversity, showing its capacity as an effective skin microbiome modulator.  Furthermore, no symptoms of irritation or allergy were found to occur based on the results of a skin patch test containing the PMC48 culture, which presents this probiotic as a potential skin-friendly therapeutic that can be used for the treatment of hyperpigmentation conditions (Park et al., 2024). Conclusions: P. acidilactici PMC48 shows promise as a potential probiotic for the treatment of hyperpigmentation through the active inhibition of the melanogenesis pathway and degradation of melanin. It also shows evidence of being a safe treatment option that does not compromise skin health or microbiome stability in patients (Park et al., 2024). Study No. 3: A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face: Clinical evidence and mechanistic understanding by computational biology and optical biopsy (Bhardwaj et al. , 2024) The aim of this study was to investigate and clinically test a novel trichloroacetic acid (TCA) and hydroquinone (HQ)-free multi-acid synergistic technology (MAST) for the reduction of visible hyperpigmentation on the face as a safer alternative to traditional treatments that can often be damaging to people of colour (Bhardwaj  et al., 2024). Results: Using enzyme assays and computational biology, the researchers were able to identify a synergistic mixture of four different acids possessing either peeling (lactic, mandelic, and pyruvic acids or depigmentation (tranexamic) functions for the effective treatment of facial hyperpigmentation in all Fitzpatrick skin types.  The MAST peel was found to demonstrate superior melanin-inhibitive qualities after single application compared to a commercial HQ-KA peel, with 17% reduction in melanin intensity compared to only 1% after the HQ-KA peel, and a significant reduction (50 - 58%) in the expression of genes involved in melanin production. No adverse events were reported by participants receiving the MAST peel treatment, with no frosting or downtime required for recovery. Furthermore, a clear decrease in brown patches and redness was observed in most cases, and global improvement in most subjects for parameters such as uneven pigmentation/skin tone, skin texture, redness (Erythema) and fine lines/wrinkles was also reported. Use of the peel did not induce skin microbiome dysbiosis. However, the researchers did note a noticeable increase in species diversity after chemical peeling accompanied by a decrease in C. acnes  abundance, although these did not induce any harmful effects overall in participants (Bhardwaj  et al., 2024). Conclusion: The multi-acid MAST peel demonstrates high potential as an inclusive treatment for the treatment of hyperpigmentation disorders through its superior anti-pigmentation activity on human skin compared to a commercial peel, as well as clinical efficacy with minimum downtime. Its lack of dysbiotic side-effects also show this technology to be a microbiome-friendly alternative to current conventional hyperpigmentation treatments (Bhardwaj  et al., 2024). Strengths & Limitations of Research Strengths Existing studies have demonstrated a possible relationship between microbiome composition and hyperpigmentation strength, with such findings supporting the development of microbiome-based therapies as well as laying important groundwork for future mechanistic exploration The association between microbiome composition and hyperpigmentation might pave the way for the development of personalised treatments or non-invasive diagnostics to identify microbial biomarkers of hyperpigmentation that can be used to inform precision therapies or prevention strategies for this condition Limitations There exists a very limited number of studies investigating hyperpigmentation and the skin microbiome, meaning research and information regarding the interplay between the two remains limited. More research needs to be conducted before any concrete conclusions can be drawn regarding the microbiome's effect on the development of hyperpigmentation conditions. This gap also restricts the development of microbiome-targeted therapeutics for hyperpigmentation. Further longitudinal studies are also needed to capture the dynamic nature of the skin microbiome in hyperpigmentation over time, including during flare-ups, treatment, or with seasonal/life changes. Interventional studies using prebiotics, probiotics, or even postbiotics, also remain sparse, which contributes to the limitation in therapeutic development. Many microbiome-hyperpigmentation studies focus on specific ethnic groups or skin types, which may not be generalisable due to ethnic variations in both microbiome composition or pigmentation biology. More inclusive studies are necessary to improve reproducibility of results, and overall efficacy of treatment applications. Related Research & Future Directions   Further studies seeking to distinguish between photoaging and chronological aging effects on hyperpigmentation development can focus on comparing the microbiomes of sun-exposed and unexposed skin as a way to elucidate differences between environmental and host intrinsic effects on skin microbiomes (Shibagaki et al. , 2017) Conducting in-depth analyses focusing on the specific action of probiotics such as PMC48 will provide a more detailed understanding of the mechanism by which these probiotics are able to degrade melanin pigments, as a way to engineer the development of more efficient probiotic strains, or identify other potential probiotic drug candidates for hyperpigmented skin (Park et al. , 2024) Similar research assessing the efficacy of MAST technology can be used for the treatment of other microbiome-associated disorders in patients with acne ( Cutibacterium acnes  phylotypes) and atopic dermatitis ( Staphylococcus aureus ) for a similar non-invasive, skin microbiome-friendly therapeutic approach (Bhardwaj et al. , 2024) Conclusion Research into the role of the skin microbiome in hyperpigmentation is still in its early stages, but emerging evidence highlights a promising link between microbial composition, skin physiology, and pigmentation outcomes. Recent studies exploring probiotic strains, such as Pediococcus acidilactici MC48 and microbiome-friendly chemical peels like MAST, demonstrate the therapeutic potential of modulating the skin microbiome to reduce hyperpigmentation safely and effectively. Meanwhile, observational studies have revealed distinct microbial patterns associated with different pigmentation levels, pointing to new avenues for diagnostics and targeted interventions. While current limitations, including a lack of longitudinal studies and population diversity, must be addressed, this growing body of research paves the way for more inclusive, microbiome-informed treatments that support both skin health and pigmentation balance. References Bhardwaj, V. et al.  (2024) ‘A novel professional-use synergistic peel technology to reduce visible hyperpigmentation on face: Clinical evidence and mechanistic understanding by computational biology and optical biopsy’, Experimental Dermatology , 33(4), p. e15069. Available at:   https://doi.org/10.1111/exd.15069 . Definition of hyperpigmentation - NCI Dictionary of Cancer Terms - NCI  (2011). Available at:   https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hyperpigmentation  (Accessed: 24 July 2025). Dimitriu, P.A. et al.  (2019) ‘New Insights into the Intrinsic and Extrinsic Factors That Shape the Human Skin Microbiome’, mBio , 10(4), p. 10.1128/mbio.00839-19. Available at:   https://doi.org/10.1128/mbio.00839-19 . Foundation, B.S. (no date) Melasma – British Skin Foundation . Available at:   https://knowyourskin.britishskinfoundation.org.uk/condition/melasma/  (Accessed: 24 July 2025). Lawrence, E., Syed, H.A. and Al Aboud, K.M. (2025) ‘Postinflammatory Hyperpigmentation’, in StatPearls . Treasure Island (FL): StatPearls Publishing. Available at:   http://www.ncbi.nlm.nih.gov/books/NBK559150/  (Accessed: 24 July 2025). Li, Z. et al.  (2020) ‘New Insights Into the Skin Microbial Communities and Skin Aging’, Frontiers in Microbiology , 11. Available at:   https://doi.org/10.3389/fmicb.2020.565549 . Lunjani, N. et al.  (2021) ‘Mechanisms of microbe-immune system dialogue within the skin’, Genes & Immunity , 22(5), pp. 276–288. Available at:   https://doi.org/10.1038/s41435-021-00133-9 . Meisel, J.S. et al.  (2018) ‘Commensal microbiota modulate gene expression in the skin’, Microbiome , 6(1), p. 20. Available at:   https://doi.org/10.1186/s40168-018-0404-9 . Park, H.-A. et al.  (2024) ‘Clinical effect of Pediococcus acidilactici PMC48 on hyperpigmented skin’, Journal of Cosmetic Dermatology , 23(1), pp. 215–226. Available at:   https://doi.org/10.1111/jocd.15891 . Plensdorf, S., Livieratos, M. and Dada, N. (2017) ‘Pigmentation Disorders: Diagnosis and Management’, American Family Physician , 96(12), pp. 797–804. Shibagaki, N. et al.  (2017) ‘Aging-related changes in the diversity of women’s skin microbiomes associated with oral bacteria’, Scientific Reports , 7(1), p. 10567. Available at:   https://doi.org/10.1038/s41598-017-10834-9 . Zanchetta, C. et al.  (2022) ‘Bacterial taxa predictive of hyperpigmented skins’, Health Science Reports , 5(3), p. e609. Available at:   https://doi.org/10.1002/hsr2.609 .

Acne vulgaris is a prevalent condition impacting seborrheic (oily) areas of the body such as the face, chest, and back. Its onset has been linked to a myriad of factors from excess sebum production, follicular hyperkeratinization (i.e., abnormally rapid production and shedding of skin cells causing blockage of sebaceous hair follicles), and host inflammatory responses (Niedźwiedzka et al. , 2024). The skin resident bacterium Cutibacterium acnes  (formerly known as Propionibacterium acnes ) is another factor of interest; its involvement in various infections of the skin has led to its discovery as an opportunistic pathogen that likely plays a role in acne pathogenesis. The pathogenicity of these particular acne-causing strains is likely related to their ability to form biofilms and produce pro-inflammatory enzymes that worsen acne symptoms, as not all C. acnes  strains produce these effects and many actively contribute to maintaining skin microbiome balance and homeostasis (Niedźwiedzka et al. , 2024). Similar disruptions to skin microbiome balance have also been noted to be caused by conventional acne treatments like oral antibiotics, benzoyl peroxide, and topical retinoids targeting C. acnes  for removal. This has produced a demand for alternative, microbiome-friendly therapeutic approaches that reduce severity of acne symptoms while maintaining and restoring microbiome balance (Niedźwiedzka et al. , 2024). This review sought to provide a comprehensive overview of the current state of research in traditional and emerging treatments to combat acne, including the potential of microbiome-targeted therapies such as probiotics and phage treatment as an alternative to conventional antibiotic-based approaches. It also explored the dynamic between different skin pathogen populations, and how they might be able to influence one another’s susceptibility to treatment (Niedźwiedzka et al.,  2024). Results Among affecting C. acnes  bacteria, use of antibiotics has also increased rates of resistance in other resident skin microbiome species such as S. epidermidis , another common group found on the skin, with one study reporting high resistance rates of S. epidermidis  acne isolates to an array of antibiotics like tetracycline (31%), doxycycline (27%), clindamycin (33%), and erythromycin (58%) (Moon et al. , 2012).  Other studies on C. acnes  biofilm formation report the ability of these microbial structures to enhance susceptibility to antibiotics for other groups of bacteria, with reduced size and restricted formation of Staphylococcus aureus  (another skin pathogen) biofilms being observed upon exposure to these bacteria. These S. aureus biofilms exhibited increased susceptibility to multiple antibiotics such as ciprofloxacin and rifampicin upon C. acnes  exposure, presenting interesting implications for the efficacy of antibiotic treatments during skin pathobiont coinfection (Abbott et al. , 2022). Some of the global effects of antibiotic use beyond treating skin may extend to influencing gut microbiome composition, with previous studies reporting significant disruptions to gut microbiome structure during antibiotic use. Sarecycline had the most minimal impact, allowing bacterial populations to recover after treatment, while minocycline depleted multiple beneficial groups such as Lactobacillus, Ruminococcaceae  and Clostridiaceae that managed to only partially recover post-treatment (Moura et al. , 2022). Similar disruptions have been linked to the onset of gastrointestinal disorders like irritable bowel disease, demonstrating the importance of considering whole body effects when administering antibiotic acne treatments. Probiotics represent an alternative emerging therapy area for the treatment of acne without antibiotics. Topical probiotic formulations consisting of beneficial bacterial species such as Lactobacillus and Bifidobacterium are capable of increasing skin ceramide production, reducing inflammation, and improving skin barrier function against pathogens to improve acne symptoms and promote microbiome health and skin immunity. They have also demonstrated significant efficacy in reducing the growth of acne-associated bacteria like C. acnes , showing potential as a treatment for symptoms of acne. Topical probiotic formulations like SkinDuo™ containing the strain Lactiplantibacillus plantarum  LP01 have shown significant efficacy in reducing the growth of acne associated bacteria like C. acnes  and S. epidermidis , as well as a reduction in the production of inflammatory markers such as IL-1α, IL-6, and IL-8 that worsen the appearance of acne lesions, as well as significantly reducing lipid production (Podrini et al.,  2023). Oral probiotics containing Lacticaseibacillus rhamnosus  and Arthrospira platensis  were capable of reducing the number of lesions on the skin of patients in one clinical trial, with a greater proportion of patients receiving probiotic treatment demonstrating a reduction in both total and non-inflammatory acne lesions compared to the placebo group. The probiotic treatment also reduced the overall severity of acne in patients (Eguren et al., 2024).  Phage therapy is another emergent treatment that seeks to reduce the severity of acne by harnessing the power of viruses known as bacteriophages (or, phages) that specifically infect bacterial cells. This makes them an ideal candidate for acne therapy, as they offer the option of targeting only acne-associated pathogenic C. acnes  strains without disrupting the overall balance of the skin microbiome, unlike many broad-spectrum antibiotics that indiscriminately target both harmful and beneficial bacteria. A recent preclinical study investigating the effectiveness of this treatment found that topical application of C. acnes -targeting phages resulted in a marked reduction of bacterial load and inflammation in C. acnes -induced acne-like lesions (Rimon et al. , 2023), demonstrating the potential for this type of phage therapy to act as either adjunct or alternative to existing antibiotic approaches combating symptoms of acne (Niedźwiedzka et al.,  2024). Table summarising the effects of various acne treatments on the skin microbiome Future Directions Another bioactive approach that is currently emerging as a potential therapy for acne treatment is the use of prebiotic compounds that selectively promote the growth of certain beneficial strains or species of bacteria on the skin by providing key nutrients. Current prebiotics of interest include fructooligosaccharides (FOS) and galactooligosaccharides (GOS) (Niedźwiedzka et al.,  2024). Synbiotics (the combination of probiotics and prebiotics) also present an emerging area of research. These work by boosting the activity of beneficial microbes while providing essential nutrients for their growth, indicating a potential synergistic approach to managing acne symptoms (Niedźwiedzka et al.,  2024). Therapeutic formulations containing beneficial CRISPR-possessing bacteria may be used to restore balance to the skin microbiome by competing with pathogenic strains of C. acnes  to reduce their abundance, as well as inhibiting any bacteriophage-induced inflammation on the skin that could worsen acne symptoms or further disbalance the skin microbial community (Maguire and McGee, 2024). Conclusion Beyond traditional antibiotic treatments combating acne, several emergent bioactive approaches are currently being developed with promising results for reducing both the severity of acne, as well as targeting the dysbiotic mechanisms potentially underlying its pathogenesis. These offer more personalised and sustainable solutions for both acne therapy, and also the growing concern of antibiotic resistance within skin-associated microbiomes (Niedźwiedzka et al.,  2024). More research is still needed to better understand the influence and interactions of different microbial communities beyond bacteria on the skin such as fungi and viruses, and how this might impact upon traditional and alternative acne therapies in the long term as a way to facilitate the development of more effective microbiome-based treatments for acne (Niedźwiedzka et al. , 2024). Continued research into clinical trials for probiotics and phage therapies will also be necessary to help determine the most effective formulations, dosages, and methods of application for their integration into conventional acne treatment procedures (Niedźwiedzka et al. , 2024). References Abbott, C. et al.  (2022) ‘ Cutibacterium acnes  biofilm forming clinical isolates modify the formation and structure of Staphylococcus aureus  biofilms, increasing their susceptibility to antibiotics’, Anaerobe , 76, p. 102580. Available at:   https://doi.org/10.1016/j.anaerobe.2022.102580 . Eguren, C., Navarro-Blasco, A., Corral-Forteza, M., Reolid-Pérez, A., Setó-Torrent, N., García-Navarro, A., Prieto-Merino, D., Núñez-Delegido, E., Sánchez-Pellicer, P. and Navarro-López, V. (2024). A Randomized Clinical Trial to Evaluate the Efficacy of an Oral Probiotic in Acne Vulgaris. Acta Dermato-Venereologica, [online] 104, pp.adv33206–adv33206. doi: https://doi.org/10.2340/actadv.v104.33206 . Maguire, G. and McGee, S.T. (2024). NeoGenesis MB-1 with CRISPR Technology Reduces the Effects of the Viruses (Phages) Associated with Acne - Case Report. Integrative medicine (Encinitas, Calif.), [online] 23(4), pp.34–38. Available at: https://pubmed.ncbi.nlm.nih.gov/39355416/ . Moon, S.H. et al.  (2012) ‘Antibiotic resistance of microbial strains isolated from Korean acne patients’, The Journal of Dermatology , 39(10), pp. 833–837. Available at:   https://doi.org/10.1111/j.1346-8138.2012.01626.x . Moura, I.B. et al.  (2022) ‘Profiling the Effects of Systemic Antibiotics for Acne, Including the Narrow-Spectrum Antibiotic Sarecycline, on the Human Gut Microbiota’, Frontiers in Microbiology , 13. Available at:   https://doi.org/10.3389/fmicb.2022.901911 . Niedźwiedzka, A. et al.  (2024) ‘The Role of the Skin Microbiome in Acne: Challenges and Future Therapeutic Opportunities’, International Journal of Molecular Sciences , 25(21), p. 11422. Available at:   https://doi.org/10.3390/ijms252111422 . Podrini, C., Schramm, L., Marianantoni, G., Apolinarska, J., McGuckin, C., Forraz, N., Milet, C., Desroches, A.-L., Payen, P., D’Aguanno, M. and Biazzo, M. (2023). Topical Administration of Lactiplantibacillus plantarum (SkinDuoTM) Serum Improves Anti-Acne Properties. Microorganisms, [online] 11(2), p.417. doi: https://doi.org/10.3390/microorganisms11020417 . Rimon, A. et al.  (2023) ‘Topical phage therapy in a mouse model of Cutibacterium acnes-induced acne-like lesions’, Nature Communications , 14(1), p. 1005. Available at:   https://doi.org/10.1038/s41467-023-36694-8 .

Salicylic Acid Sebum regulation Salicylic acid reduces sebum production by inhibiting the AMPK–SREBP‑1 lipid synthesis pathway in human sebocytes (SEB-1), while also promoting apoptotic clearance of overactive sebaceous cells. It decreases inflammation via the NF‑κB pathway, contributing to clearer skin and reduced oiliness. Skin Cell turnover As a keratolytic agent, salicylic acid aids in the breakdown and exfoliation of dead skin cells. It gets within the pores and clears out the dirt that causes acne and blocked pores. The exfoliating action of salicylic acid promotes skin cell renewal and enhances the penetration of moisturizing substances. Skin microbiome An interesting and novel form is the Supramolecular Salicylic Acid (SSA). It decreases the abundance of acne-associated bacteria such as Ralstonia, Staphylococcus, and Phreatobacter, restoring a healthier microbiota composition similar to that of healthy controls. It slightly increases Cutibacterium levels, a genus linked to skin health, and normalizes the ratio of phyla like Firmicutes, Actinobacteria, and Proteobacteria, indicative of a balanced skin flora. The antimicrobial effects stem from SSA's ability to inhibit pathogenic bacterial colonization, regulate pH, and reduce sebaceous gland secretions, creating an environment favorable for beneficial bacteria. Additionally, SSA impacts the microbiota from the phylum to genus level, suppressing harmful genera and fostering microbial diversity, further underscoring its role in improving skin health.  Inflammation Salicylic acid downregulates proinflammatory cytokines and enzymes in both sebocytes and inflamed skin, through suppression of NF‑κB, COX‑2, and SREBP pathways, and promotes apoptosis of inflammatory cells around acne lesions. Azelaic Acid Sebum regulation Topical 20% azelaic acid treatments have demonstrated long-term sebostatic effects, helping reduce sebum levels in acne patients. One clinical study reported average sebum reductions from 195 µg/cm² to 150 µg/cm² on the forehead and cheek, persisting even three months post-treatment. Skin Cell turnover Azelaic acid (AZA) is a mild anti-keratinizing agent that reversibly slows keratinocyte growth in a dose- and time-dependent manner. It works by causing mitochondrial swelling and dilation of the rough endoplasmic reticulum in keratinocytes, disrupting their terminal differentiation. This includes delaying filaggrin production and reducing keratohyalin granules and tonofilament bundles, which are key structural elements in mature keratinocytes. AZA also temporarily inhibits DNA, RNA, and protein synthesis, affecting cell proliferation. Skin microbiome The antimicrobial activity of AZA against Propionibacterium acnes  and Staphylococcus epidermidis . The mechanism of antimicrobial action is based on the inhibition of the enzyme thioredoxin reductase of bacteria which affects the inhibition of bacterial DNA synthesis that occurs in the cytoplasm. Azelaic acid (AZA) is an effective acne treatment because it inhibits the growth of acne-causing bacteria like Cutibacterium acnes  and Staphylococcus  species without causing antibiotic resistance. It works by entering bacterial cells, lowering their internal pH, and blocking essential enzymes needed for DNA and protein synthesis, which weakens or kills the bacteria. AZA is more effective at higher concentrations and acidic pH levels. Studies have shown that AZA not only reduces harmful bacteria but also promotes a healthier balance of skin microbes, increasing beneficial bacteria like lactobacilli. Advanced formulations, such as AZA micro-nanocrystals, have demonstrated even greater antibacterial effects. Azelaic acid (15% gel) is a common and safe treatment for acne vulgaris, a condition affecting most teenagers and young adults. In a study with 55 acne sufferers using this gel daily for 28 days, researchers analyzed changes in their skin bacteria. They found that acne-affected skin had a different mix of bacteria compared to clear skin. After using the gel, the variety and balance of bacteria in acne areas improved, with a notable increase in beneficial Lactobacillus  bacteria. Harmful bacteria like Cutibacterium  and Staphylococcus  decreased slightly, making the bacterial community on treated acne skin more like that of healthy skin. This suggests that azelaic acid helps restore a healthier skin microbiome in acne patients. Inflammation Azelaic acid (AZA) reduces skin inflammation by blocking several key inflammatory processes. It inhibits the production of reactive oxygen species (ROS) from immune cells and suppresses major inflammatory signaling pathways like NF-κB and MAPK. AZA also activates anti-inflammatory receptors (PPARγ) and lowers the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNFα. Additionally, it decreases the production of inflammatory lipid compounds and inhibits toll-like receptor 2 (TLR2) along with related molecules (KLK5 and LL37), which play important roles in sustaining inflammation in conditions like acne. Together, these actions help calm and control skin inflammation. Niacinamide Sebum regulation Niacinamide helps reduce excessive sebum production, a study showed that topical 2% niacinamide significantly decreased sebum excretion after 4 weeks of use. Lowering the sebum excretion rate (SER) in Japanese individuals and casual sebum levels (CSL) in Caucasian individuals. Skin cell turnover Research shows niacinamide enhances the biosynthesis of ceramides, fatty acids, and cholesterol, key components of the skin barrier. Skin microbiome Niacinamide positively influences the skin microbiome through its broad-spectrum antimicrobial activity, which includes antibacterial, antifungal, and antiviral effects. It has demonstrated effectiveness in preventing biofilm formation and in reducing pathogens like Escherichia coli , Staphylococcus aureus , and Cutibacterium acnes , a key contributor to acne. Importantly, niacinamide does not kill bacteria directly, instead, it enhances the skin’s innate immune defenses by stimulating the production of antimicrobial peptides (AMPs), such as defensins and cathelicidins in keratinocytes, sebocytes, and neutrophils. These AMPs help maintain a healthy microbial balance on the skin by targeting both Gram-positive and Gram-negative bacteria, as well as fungi and viruses. It was also found to suppress the growth of several Candida  and Cryptococcus spp. strains and to effectively inhibit bacteria like Pseudomonas aeruginosa  and Staphylococcus aureus , as well as fungi such as Aspergillus brasiliensis . The antimicrobial action likely occurs through niacinamide binding to DNA, disrupting DNA replication and causing cell division failure. This disruption leads to DNA fragmentation, preventing the growth of harmful microorganisms.  Inflammation Niacinamide exhibits broad and multimodal anti-inflammatory activity, making it highly effective in managing inflammatory skin conditions like acne, as well as systemic inflammatory disorders. It reduces oxidative stress and reactive oxygen species (ROS), which are key triggers of inflammation, and inhibits the secretion of pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6, IL-8, and PGE2) through modulation of NFκB transcription and PARP regulation. Niacinamide influences macrophage and mast cell behavior, stabilizing these immune cells and preventing the release of inflammatory mediators such as histamine and prostaglandins. It also enhances anti-inflammatory markers like IL-10 and MRC-1, while downregulating immune overactivity, including MHC class II expression. Furthermore, it helps prevent keratinocyte and fibroblast senescence, reducing the production of inflammatory molecules associated with the senescence-associated secretory phenotype (SASP). Clinically, niacinamide has shown dose-dependent reductions in skin inflammation markers and offers anti-pruritic benefits by both calming mast cells and restoring the skin barrier via ceramide synthesis.  Retinoids Sebum regulation Topical retinoids (tretinoin) reduce sebocyte proliferation and influence differentiation via RAR/RXR receptor binding in sebaceous glands, although direct sebum output reduction is less well quantified in vivo, they visibly shrink pores and normalize gland activity. Skin cell turnover Increased epidermal cell renewal improves skin texture, diminishes hyperpigmentation, and enhances collagen and elastin deposition via fibroblast activation and inhibition of matrix metalloproteinases (MMPs). Skin microbiome Topical retinol significantly influences the skin microbiome by restructuring its composition and metabolic activity. Retinol alters microbial gene pathways, especially those involved in vitamin B synthesis and metabolism, promoting the proliferation of microbes enriched in these pathways. It stimulates the production of beneficial microbial metabolites such as apigenin and protocatechuic acid, which have antioxidant and anti-inflammatory properties. Additionally, retinol use leads to increased secretion of acidic microbial metabolites like phenylglyoxylic acid, which help lower skin pH, a critical factor in strengthening the skin barrier and supporting antimicrobial defense. Notably, the microbiome also contributes directly to retinol metabolism, with species like Corynebacterium kefirresidentii  and Sericytochromatia sp.  aiding in the oxidation of retinol to retinaldehyde, a necessary step for producing active retinoic acid. These microbes, particularly those from the Corynebacterium genus, become more functionally active or enriched after retinol application. Inflammation Modulate inflammation in the skin by directly influencing key components of the innate immune system, such as Toll-like receptors (TLRs). Retinoic acid has been shown to downregulate TLR2 and its co-receptor CD14, leading to a significant reduction, up to 74% in TLR2-induced pro-inflammatory cytokine (IL-6) production in human monocytes. Since TLR2 plays a critical role in initiating immune responses to bacterial components, such as those from Staphylococcus  species, its suppression by retinoids may help reduce inflammatory responses in skin conditions like acne and dermatitis. Additionally, retinoic acid signaling is activated downstream of TLR3, which responds to double-stranded RNA from damaged skin or viral infections. In this context, TLR3 activation induces intrinsic RA synthesis that promotes wound healing and hair follicle regeneration, further linking RA to immune-regulated skin repair processes.  Benzoyl peroxide Sebum regulation Benzoyl peroxide has been shown to decrease metabolism of sebaceous gland cells in humans but whether sebum production is actually decreased is controversial. Free fatty acids decrease in sebum of human patients treated with benzoyl peroxide, presumably because of its antibacterial effect, as bacterial lipases are responsible for production of free fatty acids.  Skin cell turnover Benzoyl peroxide is also believed to have a follicular flushing action. Skin microbiome Benzoyl peroxide (BPO) impacts the skin microbiome by generating reactive oxygen species (ROS) that damage bacterial proteins, effectively reducing the overall bacterial load on the skin, like Cutibacterium acnes  and Staphylococcus . This process is enhanced by natural skin lipids and is independent of bacterial structure, allowing BPO to act broadly against many microorganisms.  Inflammation Benzoyl peroxide (BPO) helps reduce skin inflammation primarily by lowering the number of acne-causing bacteria, such as Cutibacterium acnes , which are known to trigger immune responses in the skin. By killing these bacteria through the release of reactive oxygen species (ROS), BPO reduces the production of inflammatory molecules (cytokines). Additionally, BPO has been shown to directly suppress certain inflammatory pathways, such as neutrophil activity and oxidative stress. References Bilal H, Xiao Y, Khan MN, Chen J, Wang Q, Zeng Y, Lin X. Stabilization of Acne Vulgaris-Associated Microbial Dysbiosis with 2% Supramolecular Salicylic Acid. Pharmaceuticals (Basel). 2023 Jan 8;16(1):87. doi: 10.3390/ph16010087. PMID: 36678584; PMCID: PMC9864713.  Brammann C, Müller-Goymann CC. An update on formulation strategies of benzoyl peroxide in efficient acne therapy with special focus on minimizing undesired effects. Int J Pharm. 2020 Mar 30;578:119074. doi: 10.1016/j.ijpharm.2020.119074. Epub 2020 Jan 23. PMID: 31982561. Decoding the anti-aging effect of retinol in reshaping the human skin microbiome niches. Minyan Gui, Jingmin Cheng, Xueni Lin, Danni Guo, Qi Zhou, Wentao Ma, Hang Yang, Xueqing Chen, Zhao Liu, Lan Ma, Xinhui Xing, Peng Shu, Xiao Liu bioRxiv 2024.06.26.600860; doi: https://doi.org/10.1101/2024.06.26.600860 Draelos ZD, Matsubara A, Smiles K. The effect of 2% niacinamide on facial sebum production. J Cosmet Laser Ther. 2006 Jun;8(2):96-101. doi: 10.1080/14764170600717704. PMID: 16766489. Endly DC, Miller RA. Oily Skin: A review of Treatment Options. The Journal of Clinical and Aesthetic Dermatology. 2017 Aug;10(8):49-55. PMID: 28979664; PMCID: PMC5605215. Feng X, Shang J, Gu Z, Gong J, Chen Y, Liu Y. Azelaic Acid: Mechanisms of Action and Clinical Applications. Clin Cosmet Investig Dermatol. 2024 Oct 22;17:2359-2371. doi: 10.2147/CCID.S485237. PMID: 39464747; PMCID: PMC11512533. Lu J, Cong T, Wen X, Li X, Du D, He G, Jiang X. Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes. Exp Dermatol. 2019 Jul;28(7):786-794. doi: 10.1111/exd.13934. Epub 2019 May 15. PMID: 30972839. Măgerușan ȘE, Hancu G, Rusu A. A Comprehensive Bibliographic Review Concerning the Efficacy of Organic Acids for Chemical Peels Treating Acne Vulgaris. Molecules. 2023 Oct 22;28(20):7219. doi: 10.3390/molecules28207219. PMID: 37894698; PMCID: PMC10608815.  Marques C, Hadjab F, Porcello A, Lourenço K, Scaletta C, Abdel-Sayed P, Hirt-Burri N, Applegate LA, Laurent A. Mechanistic Insights into the Multiple Functions of Niacinamide: Therapeutic Implications and Cosmeceutical Applications in Functional Skincare Products. Antioxidants (Basel). 2024 Mar 30;13(4):425. doi: 10.3390/antiox13040425. PMID: 38671873; PMCID: PMC11047333. Mueller, R. S. (2008). Topical dermatological therapy. In Elsevier eBooks (pp. 546–556). https://doi.org/10.1016/b978-070202858-8.50026-9 Roche FC, Harris-Tryon TA. Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative Review. Nutrients. 2021 Jan 21;13(2):302. doi: 10.3390/nu13020302. PMID: 33494277; PMCID: PMC7909803. Sauer N, Oślizło M, Brzostek M, Wolska J, Lubaszka K, Karłowicz-Bodalska K. The multiple uses of azelaic acid in dermatology: mechanism of action, preparations, and potential therapeutic applications. Postepy Dermatol Alergol. 2023 Dec;40(6):716-724. doi: 10.5114/ada.2023.133955. Epub 2024 Jan 8. PMID: 38282869; PMCID: PMC10809820. Szymańska A, Budzisz E, Erkiert-Polguj A. Long-term effect of azelaic acid peel on sebum production in acne. Dermatol Ther. 2022 Jan;35(1):e15186. doi: 10.1111/dth.15186. Epub 2021 Nov 17. PMID: 34731527. Tanno O, Ota Y, Kitamura N, Katsube T, Inoue S. Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier. Br J Dermatol. 2000 Sep;143(3):524-31. doi: 10.1111/j.1365-2133.2000.03705.x. PMID: 10971324. Yu, Wenxin & Shen, Huchi & Cai, Beilei & Xie, Yuanruo & Wang, Yue & Wang, Jing. (2024). 15% Azelaic acid gel modify the skin microbiota of acne vulgaris. Journal of Dermatologic Science and Cosmetic Technology. 1. 100041. 10.1016/j.jdsct.2024.100041.  Zasada M, Budzisz E. Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol. 2019 Aug;36(4):392-397. doi: 10.5114/ada.2019.87443. Epub 2019 Aug 30. PMID: 31616211; PMCID: PMC6791161. Zegarska, Barbara & Rudnicka, Lidia & Narbutt, Joanna & Baranska-Rybak, Wioletta & Bergler-Czop, Beata & Chlebus, Ewa & Czarnecka-Operacz, Magdalena & Czuwara, Joanna & Kaszuba, Andrzej & Lesiak, Aleksandra & Nowicki, Roman & Owczarczyk-Saczonek, Agnieszka & Placek, Waldemar & sokolowska-wojdylo, Malgorzata & Szepietowski, Jacek. (2023). Dermocosmetics in the management of acne vulgaris. Recommendations of the Polish Dermatological Society. Part II. Dermatology Review. 110. 593-601. 10.5114/dr.2023.134675.   Ziklo N, Bibi M, Sinai L, Salama P. Niacinamide Antimicrobial Efficacy and Its Mode of Action via Microbial Cell Cycle Arrest. Microorganisms. 2024 Aug 2;12(8):1581. doi: 10.3390/microorganisms12081581. PMID: 39203423; PMCID: PMC11356291.

Introduction Besides the gut, the epidermis possesses one of the largest surface areas for direct contact and colonisation with microorganisms, with approximately 10^12 bacteria inhabiting the skin, compared with 10^14 in the intestines. Recent studies have geared focus towards understanding the immunomodulatory potential of these two organs on each other, with findings that point to the ability of the gut microbiota to alter the function of the immune system to disrupt skin homeostasis, and subsequently balance of the skin microbiota (Sánchez-Pellicer et al. , 2022). Acne vulgaris is one such condition thought to be driven by this complex bidirectional interaction, where it is characterised by inflammation of the pilosebaceous units of the skin. Onset of this condition has been noted to coincide with puberty and subsequent elevated sebum production, resulting in a higher prevalence in groups such as adolescents and young adults, and the appearance of comedones, papules, pustules, nodules, or scars on the skin (Sánchez-Pellicer et al. , 2022). While the specific mechanism by which the gut microbiota enacts such control over the development of acne has yet to be properly established, several studies have noted a relationship between intestinal dysbiosis and presence of acne on the skin. The mTOR (mammalian target of rapamycin) pathway is also thought to play a role, with defects in this pathway disrupting processes essential to skin homeostasis and even modifying gut microbiome composition, which may inadvertently trigger acne pathogenesis or inflammation (Sánchez-Pellicer et al. , 2022). The objective of this paper was to review the effectiveness of probiotic treatments as adjuvant or alternative therapies in treating this skin condition by modulating the gut–skin axis possibly involved in regulating the cutaneous microbiome. It also examines the influence of lifestyle factors such as diet that act along the gut-skin axis to influence skin homeostasis and acne pathogenesis (Sánchez-Pellicer et al., 2022). Results The ability of certain probiotics to produce antimicrobial substances may permit control of acne symptoms by inhibiting the growth of C. acnes . Strains of bacteria such as Streptococcus salivarius  (Bowe et al., 2006), Lactococcus sp.  HY 449 (Oh et al., 2006), and Lactobacillus salivarius  LS03 (Deidda et al., 2018) secrete bacteriocins (a type of antimicrobial peptide) that can exert this inhibitory effect. Glycerol fermentation by S. epidermidis  is capable of producing succinic acid that can restrict C. acnes  growth by decreasing the intracellular pH of the C. acnes  cells and interfering with their metabolism and ability to properly function (Wang et al., 2014). Other probiotic species like Streptococcus thermophilus  (Di Marzio et al., 1999) can increase production of ceramides like phytosphingosine (Pavicic et al., 2007) that promote water retention in the skin, anti-inflammation, and antimicrobial activity against C. acnes . These three factors act to reduce severity of acne symptoms and lesions. Biofilms, which are an aggregate community of bacterial cells contained within a polymer matrix that adheres to the skin surface, are another feature of C. acnes  that increases its resistance to antibiotics by preventing them from directly interacting with any of the bacterial cells contained within the matrix. Lactobacillus and Bifidobacterium species have demonstrated the ability to disrupt the biofilms of pathogenic bacteria such as C. acnes  to reduce their virulence and possibly increase their sensitivity to other treatments (Lopes et al., 2016). Probiotics can be administered either orally or topically, with multiple trials reporting successes in treating acne using either treatment.  Oral probiotics have the potential to reduce symptoms associated with acne through modulation of the intestinal microbiota and promotion of anti-inflammatory effects. 12-weeks of orally administering a probiotic mixture containing Lactobacillus acidophilus, Lactobacillus bulgaricus , and Bifidobacterium bifidum , in combination with a minocycline antibiotic found that within 8 weeks, patients in the combination group demonstrated significantly better efficacy in lesion and inflammation reduction than groups receiving either probiotic or antibiotic alone (Jung et al. , 2013). Topical treatments instead work by directly inhibiting the growth of C. acnes  in the pilosebaceous unit, with one clinical trial reporting a similar reduction in the appearance of mild-to-moderate acne lesions on the skins of patients treated with either a 2.5% benzoyl peroxide lotion, or a probiotic-derived lotion containing Lactobacillus paracasei MSMC 39-1 (a strain known to restrict C. acnes  growth) after 4-weeks of treatment. However, the group receiving probiotic-derived lotion reported fewer treatment-associated side effects than the 2.5% benzoyl peroxide group, highlighting its potential as a safe yet effective alternative (Sathikulpakdee et al., 2022). A high fat, Western diet typically associated with high consumption of ultra processed foods and sugar leads to a loss of diversity of gut microbiota, and can promote formation of acne lesions. Overconsumption of red meat, which is a typical feature of the Western diet, stimulates the mTOR pathway to increase the rate of lipogenesis of the sebaceous gland and subsequent inflammation. This demonstrates the ability of the gut microbiome to shape the acne inflammatory response, and highlights the importance of maintaining balance along the gut-skin axis through diet (Sánchez-Pellicer et al., 2022). Table summarising the effects of various probiotic treatments on the skin microbiome Future Directions Postbiotic formulations containing the metabolic byproducts or lysates of bacteria have shown promise as another potential bioactive treatment for acne by promoting antibacterial, anti-inflammatory, and immunomodulatory effects. The lack of live bacteria (unlike in probiotics) also makes these formulations suitable for those with weakened immune systems (Prajapati et al., 2025). Genetic engineering of probiotic strains, using approaches like the CRISPR-Cas9 system, can be used to improve the stability, specificity, and functionality of these bacteria during targeted therapeutic delivery for more effective results in treating diseases such as acne, as well as developing customised probiotics for more personalised therapies (Ma et al., 2022). Conclusions The gut-skin axis plays a crucial role in maintaining skin homeostasis and overall balance of microbial communities inhabiting the skin, something that becomes especially clear when taking lifestyle factors such as diet into account, with a high fat, Western style diet triggering acne pathogenesis, and further pointing to gut influence in modulating skin health. Utilising this dynamic to promote skin health and reduce acne symptoms can be achieved by targeting the gut microbiome in a manner that induces positive downstream effects in the skin. Oral probiotics in particular show promise as effective treatments for the treatment of acne that work by modulating the gut-skin axis. Topical probiotics show similar potential, although these bypass the gut-skin axis in most cases to directly tackle skin pathogens. Clinical trials looking to evaluate the effectiveness of topical and oral probiotics in treating acne remain scarce, with many conducted thus far involving in vitro  or animal models that do not accurately reflect human biology. Further studies are also needed to properly elucidate the exact mechanisms by which this intestinal modulation is able to influence acne progression along the skin as a way to aid the development of more effective oral treatments (Sánchez-Pellicer et al. , 2022). References Bowe, W.P., Filip, J.C., DiRienzo, J.M., Volgina, A. and Margolis, D.J. (2006). Inhibition of propionibacterium acnes by bacteriocin-like inhibitory substances (BLIS) produced by Streptococcus salivarius. Journal of drugs in dermatology: JDD, [online] 5(9), pp.868–870. Available at: https://pubmed.ncbi.nlm.nih.gov/17039652/ . Deidda, F., Amoruso, A., Nicola, S., Graziano, T., Pane, M. and Mogna, L. (2018). New Approach in Acne Therapy. Journal of Clinical Gastroenterology, 52(Supplement 1), pp.S78–S81. doi: https://doi.org/10.1097/mcg.0000000000001053 . Di Marzio, L., Cinque, B., De Simone, C. and Cifone, M.G. (1999). Effect of the Lactic Acid BacteriumStreptococcus thermophilus on Ceramide Levels in Human KeratinocytesIn Vitro and Stratum Corneum In Vivo. Journal of Investigative Dermatology, 113(1), pp.98–106. doi: https://doi.org/10.1046/j.1523-1747.1999.00633.x .  Jung, G.W. et al.  (2013) ‘Prospective, Randomized, Open-Label Trial Comparing the Safety, Efficacy, and Tolerability of an Acne Treatment Regimen with and without a Probiotic Supplement and Minocycline in Subjects with Mild to Moderate Acne’, Journal of Cutaneous Medicine and Surgery , 17(2), pp. 114–122. Available at:   https://doi.org/10.2310/7750.2012.12026 . Lopes, E.G., Moreira, D.A., Gullón, P., Gullón, B., Cardelle-Cobas, A. and Tavaria, F.K. (2016). Topical application of probiotics in skin: adhesion, antimicrobial and antibiofilm in vitro assays. Journal of Applied Microbiology, 122(2), pp.450–461. doi: https://doi.org/10.1111/jam.13349 . Ma, J., Lyu, Y., Liu, X., Jia, X., Cui, F., Wu, X., Deng, S. and Yue, C. (2022). Engineered probiotics. Microbial Cell Factories, 21(1). doi: https://doi.org/10.1186/s12934-022-01799-0 . Oh, S., Kim, S.-H., Ko, Y., Sim, J.-H., Kim, K.S., Lee, S.-H., Park, S. and Kim, Y.J. (2006). Effect of bacteriocin produced by Lactococcus sp. HY 449 on skin-inflammatory bacteria. Food and Chemical Toxicology, 44(4), pp.552–559. doi: https://doi.org/10.1016/j.fct.2005.08.030 . Pavicic, T., Wollenweber, U., Farwick, M. and Korting, H.C. (2007). Anti-microbial and -inflammatory activity and efficacy of phytosphingosine: an in vitro and in vivo study addressing acne vulgaris. International Journal of Cosmetic Science, 29(3), pp.181–190. doi: https://doi.org/10.1111/j.1467-2494.2007.00378.x . Prajapati, S.K., Lekkala, L., Yadav, D., Jain, S. and Yadav, H. (2025). Microbiome and Postbiotics in Skin Health. Biomedicines, [online] 13(4), p.791. doi: https://doi.org/10.3390/biomedicines13040791 . Sánchez-Pellicer, P. et al.  (2022) ‘Acne, Microbiome, and Probiotics: The Gut–Skin Axis’, Microorganisms , 10(7), p. 1303. Available at:   https://doi.org/10.3390/microorganisms10071303 . Sathikulpakdee, S., Kanokrungsee, S., Vitheejongjaroen, P., Kamanamool, N., Udompataikul, M. and Taweechotipatr, M. (2022). Efficacy of probiotic‐derived lotion from Lactobacillus paracasei MSMC 39‐1 in mild to moderate acne vulgaris, randomized controlled trial. Journal of Cosmetic Dermatology, 21(10), pp.5092–5097. doi: https://doi.org/10.1111/jocd.14971 . Wang, Y., Kuo, S., Shu, M., Yu, J., Huang, S., Dai, A., Two, A., Gallo, R.L. and Huang, C.-M. (2014). Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris. Applied Microbiology and Biotechnology, [online] 98(1), pp.411–424. doi: https://doi.org/10.1007/s00253-013-5394-8 .

Introduction Acne vulgaris (i.e., acne) is a chronic inflammatory condition of the skin affecting an estimated 20.5% of the global population (Saurat et al.,  2024) at a rate that has steadily increased over the last few decades from 8563.4 per 100 000 population in 1990 to 9790.5 per 100 000 population in 2021 among those aged 10 - 24 years (Zhu et al., 2024). Pathogenesis of this skin disorder has been linked to hyper-production of sebum, abnormal production and shedding of skin cells that causes blockage of hair follicles, and host inflammatory responses. Recent evidence also points to the influence of skin-associated microorganisms in triggering onset of this disease. The bacterium Cutibacterium acnes  inhabits the lipid-rich environment of sebaceous glands, and can be considered either a skin commensal or pathogen depending on specific strain (Niedźwiedzka et al. , 2024), with much evidence demonstrating a strong association between the proliferation of certain C. acnes  strains and the stimulation of multiple inflammatory pathways that exacerbate acne symptoms (Dreno et al. , 2024). The conventional approach to combating acne is through administration of antibiotics like macrolides, clindamycin, and tetracyclines that are active on C. acnes  at the expense of depleting the rest of the skin microbiome. These treatments can be administered either orally or topically, with the former producing anti-inflammatory effects and latter possessing more direct antimicrobial properties. However, increasing global incidences of antibiotic resistance among some strains as the result of frequent and long-term use of these treatments has led to concerns over the sustainability of such approaches, and has broached discussion into the development of alternative anti-acne therapies. This review article sought to summarise recent studies looking at skin microbiome dynamics in acne while assessing the effectiveness of antibiotic treatment in combating this disorder as a way to better understand the relationship between acne, microbiome, and antibiotics. It also explored the potential of novel non-antibiotic therapies in effectively combating growth of acne-associated bacteria (Xu and Li, 2019). Results Long-term use of macrolides has facilitated the increased emergence of macrolide-resistant C. acnes  strains, with resistance to macrolides such as erythromycin and azithromycin reaching over 50% (Walsh, Efthimiou and Dréno, 2016) and up to 100% (Sardana et al. , 2016), respectively, in some studies. Similar effects have been in clindamycin, with strain resistance increasing from 4% in 1999 (Kurokawa, Nishijima and Kawabata, 1999) to 90.4% in 2016 (Sardana et al. , 2016) and some reports emerging of up to 52% of acne patients carrying at least one strain of clindamycin-resistant C. acnes  (Lomholt and Kilian, 2014).  Similarly, prolonged and excessive use of other antibiotics such as tetracyclines has reportedly also led to a rise in C. acnes  resistance up to 30% across different geographical regions. Even after termination of antibiotic treatment, resistant strains may still continue to persist on the skin for a long while after, leading to the possible recurrence of acne and reduced efficacy of any future treatments to alleviate the condition (Xu and Li, 2019).  Other groups of skin bacteria have also demonstrated resistance to macrolide and clindamycin classes of antibiotics, with 30% of Staphylococcus epidermidis  isolates from acne patients showing resistance to erythromycin, roxithromycin, and clindamycin. There have also been reports of correlation in resistance between different species of antibiotic bacteria on the skin, with more than 80 % of patients carrying clindamycin-resistant C. acnes  also carrying strains of clindamycin-resistant S. epidermidis  in one study (Nakase et al.,  2014) .   While the effects of tetracyclines on skin bacteria other than C. acnes  has not been as thoroughly investigated, some evidence points to the efficacy of new members of tetracyclines, like lymecyclin, in acne treatment. One study demonstrated a decrease in clinical acne grades and the relative abundance of Cutibacterium  on the cheeks of acne patients after 6 weeks of lymecyclin treatment. However, the relative abundance of other groups like Streptococcus, Staphylococcus, Micrococcus , and Corynebacterium increased (Kelhälä et al ., 2017). Some suggested solutions to reduce the emergence of antibiotic resistance includes combining topical antibiotics with benzoyl peroxide (BPO), an antimicrobial agent that can aid in reducing the total number of C. acnes  bacteria and rates of antimicrobial resistance by maximising the amount of bacteria killed (Walsh, Efthimiou and Dréno, 2016), thus reducing the probability of any cells remaining and developing resistance post-antibiotic administration (Xu and Li, 2019). Table summarising the effects of various antibiotic treatments on the skin microbiome Future Directions Other potential therapy areas beyond traditional antibiotic approaches are currently being developed to mitigate the effects of acne. One such solution that has been proposed is the use of vaccines targeting the Christie-Atkins-Munch-Petersen (CAMP) factor of C. acnes  bacteria, with more clinical research required before their development (Kim and Kim, 2024). Biologic treatments that involve targeting and inhibiting specific signalling proteins involved in acne-related inflammation have shown promise in reducing these symptoms. These include inhibitors such as adalimumab and secukinumab (Kim and Kim, 2024). Designed antimicrobial peptides (dAMPs) are a novel class of therapeutics that could also be used in the future for direct targeting of acne-associated C. acnes  that have already developed resistance to antibiotics to control symptoms of acne (Kim and Kim, 2024). Conclusions Antibiotics are the most common treatment against acne that work by eradicating acne-associated species of bacteria, usually C. acnes  that can trigger or exacerbate symptoms of disease. The rapid emergence of antibiotic resistance in members of the resident skin microbiota has made the development of alternative solutions that treat acne while reducing the global burden of resistance a critical goal for microbe-related disease research. Several alternatives that are currently being looked into include combining antibiotic use with topical antimicrobial agents like BPO, potential vaccination targets, and even microbiome-associated therapies (Xu and Li, 2019). Current data on the effects of several other antibiotics that may be used for the treatment of acne such as trimethoprim–sulfamethoxazole, levofloxacin, rifampin, dapsone, and metronidazole remains sparse. Future studies investigating these will help address knowledge gaps regarding the efficacy of these antibiotics in treating acne, as well as their sensitivity. Additionally, future longitudinal studies on the long-term use of alternative therapies for the treatment of acne will provide further information on how they modulate skin microbiome composition, dynamics, and overall acne symptoms within cutaneous communities (Xu and Li, 2019). References Dreno, B. et al.  (2024) ‘Acne microbiome: From phyla to phylotypes’, Journal of the European Academy of Dermatology and Venereology , 38(4), pp. 657–664. Available at:   https://doi.org/10.1111/jdv.19540 . Jean-Hilaire Saurat, Halioua, B., Baissac, C., Nuria Perez Cullell, Yaron Ben Hayoun, Marketa Saint Aroman, Taieb, C. and Charbel Skayem (2024). ‘Epidemiology of acne and rosacea: A worldwide global study’, Journal of the American Academy of Dermatology, 90(5), pp.1016–1018. doi: https://doi.org/10.1016/j.jaad.2023.12.038 . Kelhälä, H.-L., Aho, V.T.E., Fyhrquist, N., Pereira, P.A.B., Kubin, M.E., Paulin, L., Palatsi, R., Auvinen, P., Tasanen, K. and Lauerma, A. (2017). Isotretinoin and lymecycline treatments modify the skin microbiota in acne. Experimental Dermatology, 27(1), pp.30–36. doi: https://doi.org/10.1111/exd.13397 . Kim, H.J. and Kim, Y.H. (2024). Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies. International Journal of Molecular Sciences, [online] 25(10), p.5302. doi: https://doi.org/10.3390/ijms25105302 . Kurokawa, I., Nishijima, S. and Kawabata, S. (1999) ‘Antimicrobial susceptibility of Propionibacterium acnes isolated from acne vulgaris’, European journal of dermatology: EJD , 9(1), pp. 25–28. Lomholt, H.B. and Kilian, M. (2014) ‘Clonality and Anatomic Distribution on the Skin of Antibiotic Resistant and Sensitive Propionibacterium acnes’, Acta Dermato-Venereologica , 94(5), pp. 534–538. Available at:   https://doi.org/10.2340/00015555-1794 . Nakase, K., Nakaminami, H., Takenaka, Y., Hayashi, N., Kawashima, M. and Noguchi, N. (2014). Relationship between the severity of acne vulgaris and antimicrobial resistance of bacteria isolated from acne lesions in a hospital in Japan. Journal of Medical Microbiology, [online] 63(Pt 5), pp.721–728. doi: https://doi.org/10.1099/jmm.0.067611-0 . Niedźwiedzka, A. et al.  (2024) ‘The Role of the Skin Microbiome in Acne: Challenges and Future Therapeutic Opportunities’, International Journal of Molecular Sciences , 25(21), p. 11422. Available at:   https://doi.org/10.3390/ijms252111422 . Sardana, K. et al.  (2016) ‘Cross-sectional Pilot Study of Antibiotic Resistance in Propionibacterium Acnes Strains in Indian Acne Patients Using 16S-RNA Polymerase Chain Reaction: A Comparison Among Treatment Modalities Including Antibiotics, Benzoyl Peroxide, and Isotretinoin’, Indian Journal of Dermatology , 61(1), p. 45. Available at:   https://doi.org/10.4103/0019-5154.174025 . Walsh, T.R., Efthimiou, J. and Dréno, B. (2016) ‘Systematic review of antibiotic resistance in acne: an increasing topical and oral threat’, The Lancet Infectious Diseases , 16(3), pp. e23–e33. Available at:   https://doi.org/10.1016/S1473-3099(15)00527-7 . Xu, H. and Li, H. (2019) ‘Acne, the Skin Microbiome, and Antibiotic Treatment’, American Journal of Clinical Dermatology , 20(3), pp. 335–344. Available at:   https://doi.org/10.1007/s40257-018-00417-3 . Zhu, Z., Zhong, X., Luo, Z., Liu, M., Zhang, H., Zheng, H. and Li, J. (2024). Global, regional, and national burdens of acne vulgaris in adolescents and young adults aged 10-24 years from 1990 to 2021: a trend analysis. British Journal of Dermatology. Available at: https://doi.org/10.1093/bjd/ljae352 .

Scientific research has demonstrated that the human skin microbiome has been shaped by both evolutionary history and modern lifestyle changes. While we share much of our DNA with primates, our microbial communities have diverged in ways that influence skin health, immunity and even our interactions with the environment. What We Know: Despite sharing over 98% of our DNA with some primates, research on the skin microbiomes of humans, chimpanzees, gorillas, rhesus macaques and baboons shows that the human skin microbiome is uniquely distinct in both composition and diversity. This divergence is hypothesised to stem from millions of years of evolutionary changes, as well as more recent shifts in hygiene practices (Council et al., 2016). The distribution of skin glands varies among primates, particularly eccrine (sweat), apocrine (scent) and sebaceous (sebum) glands. Since these glands secrete substances that serve as nutrients for microbes, differences in their distribution are thought to play a key role in shaping the unique skin microbiomes of different primate species (Council et al., 2016). Unlike other primates, humans regularly use soaps, detergents and personal care products, significantly altering microbial communities in ways that are not observed in non-human primates (Council et al., 2016). Humans also harbour fewer environmental microbes (e.g., from soil and faeces) and have a higher dominance of Staphylococcaceae , compared to other primates. This shift raises important questions about its evolutionary significance and potential impact on skin health (Council et al., 2016). Industry Impact and Potential: These insights highlight the impact of modern personal care routines on microbial ecosystems. Studies show that regular deodorant and antiperspirant use shifts the axillary (underarm) microbiome from Corynebacterium  to Staphylococcaceae , whereas those who abstain maintain microbial profiles more similar to non-human apes (Council et al., 2016). This suggests that modern hygiene habits do more than control odour - they reshape axillary microbial ecosystems. Given that Staphylococcus  species attract mosquitoes, including malaria vectors, these shifts may have unexpected implications for both evolution and health. With growing consumer interest in product formulations that sustain microbiome integrity, there is increasing demand for products that support microbial balance. Understanding these interactions paves the way for targeted skincare and hygiene solutions that work with the microbiome rather than against it (Council et al., 2016). Our Solution: With 20,000 microbiome samples, 4,000 tested ingredients and a global network of over 10,000 testing participants, Sequential provides cutting-edge microbiome analysis services. Our commitment to preserving microbiome integrity makes us an ideal partner for developing customised microbiome-friendly products for skin, scalp and intimate care. References: Council, S.E., Savage, A.M., Urban, J.M., Ehlers, M.E., Skene, J.H.P., Platt, M.L., Dunn, R.R. & Horvath, J.E. (2016) Diversity and evolution of the primate skin microbiome. Proceedings of the Royal Society B: Biological Sciences . 283 (1822), 20152586. doi:10.1098/rspb.2015.2586.

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

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

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

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