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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.

Are you looking to test your formulation through the lens of the microbiome? Sequential is the partner you need to structure your study, recruit participants and analyze your results with our sequencing reports.

Sequential provides advanced microbiome testing for personal care products, delivering actionable insights to enhance product efficacy and consumer trust. Your Clinical Microbiome Testing Partner A trusted leader in microbiome testing and research for the personal care industry, Sequential provides cutting-edge solutions to elevate product development. Our extensive microbiome research delivers effective and actionable insights, empowering brands to create innovative, science-backed personal care products that meet consumer demands and set new standards in the market. View Services Brochure 20,000+ Microbiome Sample Database 4,000+ Ingredient Database 10,000+ Testing Participants Globally 60+ Industry Partners Who We Are Sequential is a leading provider of clinical microbiome analysis and microbiome testing services, offering a comprehensive end-to-end platform with science-backed solutions tailored for the personal care and pharmaceutical industries. Our team of award-winning scientists is dedicated to understanding the intricate relationship between the microbiome and its human host, exploring how the microbiome impacts human health and how humans, in turn, influence their microbiome. This holistic approach enables us to fully characterise human health and provide actionable insights for product innovation and efficacy. Learn More What We Offer Microbiome Testing A fully customizable microbiome study to test your product's impact in a real-life context. Formulation Support Allow our formulation experts to guide you through the process of creating a product that maintains the biome. Claims & Certification Test your formulation to understand what marketing claims you can attribute to your product. Strategic Partnerships Join us in full end-to-end partnership (testing to collaborating on white papers). Clinical Assessments Understand your product's impact on transepidermal water loss, pH, and elasticity. Study Recruitment Let us recruit candidates and carry out in-lab testing for your study to ensure controlled collection. Our Testing Capabilities Differentiate your brand by leveraging the power of skin microbiome science to deliver innovative, research-backed personal care products. Stand out from competitors with solutions supported by robust clinical research and gold-standard microbiome certification, appealing to customers seeking credible and cutting-edge personal care innovations. Harness the science of the microbiome to build trust, drive customer loyalty, and position your brand as a leader in the personal care industry. Skin Scalp Vaginal Oral What Our Clients Say “Sequential is one of the world’s most innovative Microbiome companies. The resolution at subspecies level, and to perform quantification of key vaginal microbes, in vivo , was exactly what we wanted at Curive Healthcare to know intricately how our product is working to improve women’s health.” - Matthew Line, Chief Marketing Officer at Curive Healthcare Supporting World-Class Clients & Partners Join Our Partners! Microbiome's Impact on Human Health The Role of the Skin Microbiome in Acne: Challenges and Future Therapeutic Opportunities Formulating for Results: The Key Actives Behind Effective Acne Care Acne, Microbiome, and Probiotics: The Gut–Skin Axis Read More Articles FAQ What is Sequential's testing platform? Sequential has developed the gold standard test for microbiome-friendly products, in vivo (in, or on, humans). Finally, we can give some certainty about if a product is truly affecting the microbiome. We offer a complete end-to-end solution to support microbiome-friendly claims. From consultancy and study design to our proprietary microbiome testing kits. We analyse, interpret and report our findings to meet your needs. Why is it necessary to test the microbiome in vivo? At present, there are no regulations for microbiome-related formulas that brands and formulators can follow, however, it has been universally acknowledged that the in vivo method of conducting clinical studies is becoming critical and paramount to getting marketing claims through. When regulations are introduced, which may be imminent, the in vitro system will find itself lacking, resulting in limited claims and certifications that do not hold their value. This is why, we at Sequential strive to offer an in vivo approach, knowing full well that we want our client's claims to be significantly backed by scientific and quantifiable data. What type of sequencing technology does Sequential use for analysis? We offer four types of sequencing techniques including qPCR with our Smart Probes™, 16S, ITS and Shotgun Metagenomics. Using next-generation sequencing of the collection of microorganisms found on the body, during product usage, Sequential investigates the microbial diversity, and particular microorganisms we know are important and play a role in a healthy microbiome. Does Sequential offer claims certification for tested products? We provide our clients with a certification to claim “Maintains the Microbiome” subject to in vivo testing results which can be used in communication efforts. Once your product is tested with our qPCR Smart Probes™ and has shown favourable results in supporting the microbiome, we can certify your product with our Maintains the Microbiome certification seal. We have ensured that our seal and certification are backed by quantifiable data and scientifically significant markers. The aim is to ensure our clients feel confident in making their claims and can communicate the true benefit of their microbiome formulations.

Sequential Skin has developed the Skin Microbiome Test Kit to discover the state of skin microbiomes. You can do Skin Health Check to find what your skin needs. Sequential Skin has developed the first of its kind skin health test to discover the state of individuals' skin microbiome. People can now deep dive into their Skin Profile to figure out what their skin needs. Test your skin microbiome Benefits of your Skin Profile Skin Health Understand the state of your skin through your Skin Microbiome Balance Index score Skin Traits Learn about your skin traits through our in-app quiz and solutions for healthier skin Skin Age Discover your skin age and whether or not your skin is older/younger than you are Environment Unearth how your physical environment is impacting your skin microbiome Sample Register your kit: Register your kit on our Skin Health Tracker mobile app and answer the in-app quiz. Our Testing Technology Our microbiome test is the most comprehensive test on the market. We use a method known as quantitative real-time PCR (qPCR) that looks at specific markers in your skin microbiome and how they impact your skin. Skin Health Testing Kit Partner with Sequential Skin to bring our innovative skin health test to your customers. Give them an in-depth analysis of what lies on the surface of their skin and how best to increase its overall wellbeing. Register your Interest What is Sequential's testing platform? Sequential has developed the gold standard test for microbiome-friendly products, in vivo (in, or on, humans). Finally, we can give some certainty about if a product is truly affecting the microbiome. We offer a complete end-to-end solution to support microbiome-friendly claims. From consultancy and study design to our proprietary microbiome testing kits. We analyse, interpret and report our findings to meet your needs. Why is it necessary to test the microbiome in vivo? At present, there are no regulations for microbiome-related formulas that brands and formulators can follow, however, it has been universally acknowledged that the in vivo method of conducting clinical studies is becoming critical and paramount to getting marketing claims through. When regulations are introduced, which may be imminent, the in vitro system will find itself lacking, resulting in limited claims and certifications that do not hold their value. This is why, we at Sequential strive to offer an in vivo approach, knowing full well that we want our client's claims to be significantly backed by scientific and quantifiable data. What type of sequencing technology does Sequential use for analysis? We offer four types of sequencing techniques including qPCR with our Smart Probes™, 16S, ITS and Shotgun Metagenomics. Using next-generation sequencing of the collection of microorganisms found on the body, during product usage, Sequential investigates the microbial diversity, and particular microorganisms we know are important and play a role in a healthy microbiome. Does Sequential offer claims certification for tested products? We provide our clients with a certification to claim “Maintains the Microbiome” subject to in vivo testing results which can be used in communication efforts. Once your product is tested with our qPCR Smart Probes™ and has shown favourable results in supporting the microbiome, we can certify your product with our Maintains the Microbiome certification seal. We have ensured that our seal and certification are backed by quantifiable data and scientifically significant markers. The aim is to ensure our clients feel confident in making their claims and can communicate the true benefit of their microbiome formulations.