Search Results

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 .

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. Start your Project Today! With our extensive database of more than 20,000 microbiome samples, we can gain valuable insights into the effectiveness of your formulations and personal care products. With our thorough research, we offer our clients actionable information and valuable insights. Our in vivo testing guarantees that your formulations are rigorously tested, providing you with measurable results for your personal care products.

Find answers to common questions about Sequential's microbiome testing services for personal care products. Learn more about our process, benefits, and certifications. 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.

Ensure your microbiome-centric scalp product excels. Obtain expert certification to amplify its benefits in your messaging. Contact us today. Scalp Microbiome Testing As the scalp care industry grows, consumers demand transparency from the brands formulating their products. It has become essential for formulators to create products they are willing to test to present scientifically backed data-driven evidence of their products' true effects. Sequential offers microbiome testing for your scalp care formulations, ranging from scalp serums, shampoos, conditioners, oils, etc. We are dedicated to understanding how your product interacts with the scalp and its microbes. Depending on how in-depth you want to go, we offer qPCR, 16S, ITS, and Shotgun Metagenomics. Download Case Study! Personalized Approach to Testing Unlike other methodologies present within the industry, Sequential's approach ensures that your product's data and analysis will stand the test of industry regulations when they are introduced. You can tailor your study entirely to your unique requirements. Test Products in a Real-Life Context The microbiome comprises a complex ecosystem of microorganisms that live together in a delicate balance, which is why it's best to test directly upon it directly. To fully understand the impact a product is having on the microbiome, in vivo is the only way. Collect Longitudinal Data With in vivo testing we can design your study around the extended use of a product over multiple time points. This allows us to review how a product is performing before and after usage, but also take into account its gradual impact on the microbiome. Measure Against a Control Group Measure a product against a control group that might have a different percentage of your active ingredient within its formulation or no active at all. This will allow for deeper insights into the impact of a formulation on microbial balance and diversity. 4 Sequencing Reports To Pick From Depending on your development stage and what you are interested in studying we offer qPCR, 16S, ITS, and Shotgun Metagenomics. With our qPCR Smart Probes™ we can go down to the strain level in our analysis. Personalize Your Microbiome Study! Unlike hair, the scalp is formed of a living community of microorganisms such as bacterial and fungal players that can influence the balance of the scalp microbiome, even the subtlest of imbalances can lead to issues such as dandruff, itching, and irritation, resulting in unwanted flaking. Smart Probe s ™ Our dedicated team of scientists have developed a method of evaluating microbes through our Smart Probes ™ . These refer to a panel of 20 key microbes we have specifically identified as having the most impact on scalp health. Over and above the taxonomic characterisation that 16S offers, which gives us a snapshot of all the genus present within a collected sample (Cutibacterium , Staphylococcus , etc.) our targeted approach takes it a step further, opening the lens to the species (C. acnes ), sub-species (C. acnes defendens ) and even strains within them. This is a crucial distinction as not all strains of a species behave similarly. We find that within these species there are strains associated with inflammation and strains that are commensal, and beneficial. Gold Standard Certification Sequential has developed the gold standard test for products designed to target the microbiome, in vivo (in, or on, humans). Finally, we can give some certainty about if a product is truly affecting the microbiome. Using next-generation sequencing of the collection of micro-organisms found on the body, before and after product usage, Sequential investigates the microbial balance and diversity, and particular micro-organisms we know are important and play a role in a healthy microbiome. We give you an in vivo certification that your product maintains the microbiome. And it’s not exclusive to skincare! We do this for haircare products, oral products, and vulva/vaginal microbiomes. Personalize Your Microbiome Study! Supplement Your Microbiome Study Recruitment Services Let us take care of the entire candidate recruitment process for you! View More Biophysical Assessments Increase your data on the use of your product by evaluating additional biophysical factors. View More Formulation Support Seek consultation advice for your formulation if you are re-formulating or developing a new product. View More 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.