Topical probiotic formulations containing live bacteria are being explored as treatments for skin disorders such as atopic dermatitis and acne vulgaris. Certain bacterial strains with antimicrobial and/or anti-inflammatory properties show promise as bacterial therapeutics that could improve these conditions and serve as alternatives to antibiotics, which are increasingly compromised by rising antimicrobial resistance. However, little is known about the engraftment efficacy of such bacterial strains or their impact on the native skin microbiome. In this study, we applied two different coagulase-negative staphylococcal strains, one with antimicrobial activity (Staphylococcus epidermidis 2C-5) and one lacking any activity (Staphylococcus hominis H2-S92), on human back skin of 14 healthy volunteers. Engraftment was assessed using strain-specific PCR and three amplicon-based sequencing approaches at 7 and 30 days after application. Microbial profiles shifted modestly, showing a relative increase in staphylococci and a decrease in Cutibacterium spp. S. epidermidis 2C-5 drastically increased from 0.8% pre-application to 46.9% and 12.1% at days 7 and 30, respectively. S. hominis H2-S92 showed a relative rise from 1.4% to 35.8% at day 7, declining to 2.4% by day 30. Interestingly, Staphylococcus capitis relative abundance decreased by 50-60% at the application sites. These findings indicate that both strains can temporarily engraft and competitively displace native staphylococci. S. epidermidis 2C-5 appeared to colonize more effectively, possibly due to its bacteriocin production. Neither strain affected the phylotype composition of Cutibacterium acnes, suggesting lack of reach to sebaceous follicles, C. acnes’ primary niche. This study supports the potential of staphylococcal probiotics for modulating the skin microbiome. While they may be effective for conditions involving staphylococcal dysbiosis, such as atopic dermatitis, they appear less suited for treating disorders like acne vulgaris, which are associated with C. acnes imbalance.
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Ahle, C.M., Stødkilde, K., Poehlein, A., Bömeke, M., Streit, W.R., Wenck, H., Reuter, J.H., Hüpeden, J. and Brüggemann, H., 2022. Interference and co-existence of staphylococci and Cutibacterium acnes within the healthy human skin microbiome. Communications Biology 5: 923. https://doi.org/10.1038/s42003-022-03897-6
Both, A., Huang, J., Qi, M., Lausmann, C., Weißelberg, S., Büttner, H., Lezius, S., Failla, A.V., Christner, M., Stegger, M., Gehrke, T., Baig, S., Citak, M., Alawi, M., Aepfelbacher, M. and Rohde, H., 2021. Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations. PLoS Pathogens 17: e1009304. https://doi.org/10.1371/journal.ppat.1009304.
Chen, Y.E., Fischbach, M.A. and Belkaid, Y., 2018. Skin microbiota-host interactions. Nature 553: 427-436. https://doi.org/10.1038/nature25177
Christensen, I.B., Vedel, C., Clausen, M.L., Kjærulff, S., Agner, T. and Nielsen, D.S., 2021. Targeted screening of lactic acid bacteria with antibacterial activity toward Staphylococcus aureus clonal complex type 1 associated with atopic dermatitis. Frontiers in Microbiology 12: 733847. https://doi.org/10.3389/fmicb.2021.733847
Conlan, S., Mijares, L.A., Becker, J., Blakesley, R.W., Bouffard, G.G., Brooks, S., Coleman, H., Gupta, J., Gurson, N., Park, M., Schmidt, B., Thomas, P.J., Otto, M., Kong, H.H., Murray, P.R. and Segre, J.A., NISC Comparative Sequencing Program, 2012. Staphylococcus epidermidis pan-genome sequence analysis reveals diversity of skin commensal and hospital infection-associated isolates. Genome Biology 13: R64. https://doi.org/10.1186/gb-2012-13-7-r64
Espadinha, D., Sobral, R.G., Mendes, C.I., Méric, G., Sheppard, S.K., Carriço, J.A., de Lencastre, H. and Miragaia, M., 2019. Distinct phenotypic and genomic signatures underlie contrasting pathogenic potential of Staphylococcus epidermidis clonal lineages. Frontiers in Microbiology 10: 1971. https://doi.org/10.3389/fmicb.2019.01971
Fernández-Fernández, R., Lozano, C., Eguizábal, P., Ruiz-Ripa, L., Martı́nez-Álvarez, S., Abdullahi, I.N., Zarazaga, M. and Torres, C., 2022. Bacteriocin-like inhibitory substances in staphylococci of different origins and species with activity against relevant pathogens. Frontiers in Microbiology 13: 870510. https://doi.org/10.3389/fmicb.2022.870510
Karoglan, A., Paetzold, B., Pereira de Lima, J., Brüggemann, H., Tüting, T., Schanze, D., Güell, M. and Gollnick, H., 2019. Safety and efficacy of topically applied selected Cutibacterium acnes strains over five weeks in patients with acne vulgaris: An open-label, pilot study. Acta Dermato-Venereologica 99: 1253-1257. https://doi.org/10.2340/00015555-3323
Lai, Y., Di Nardo, A., Nakatsuji, T., Leichtle, A., Yang, Y., Cogen, A.L., Wu, Z.R., Hooper, L.V., Schmidt, R.R., von Aulock, S., Radek, K.A., Huang, C.M., Ryan, A.F. and Gallo, R.L., 2009. Commensal bacteria regulate Toll-like receptor 3-dependent inflammation after skin injury. Nature Medicine 15: 1377-1382. https://doi.org/10.1038/nm.2062
Månsson, E., Bech Johannesen, T., Nilsdotter-Augustinsson, Å., Söderquist, B. and Stegger, M., 2021. Comparative genomics of Staphylococcus epidermidis from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence. Microbial Genomics 7: 000504. https://doi.org/10.1099/mgen.0.000504
Nakatsuji, T., Chen, T.H., Butcher, A.M., Trzoss, L.L., Nam, S.J., Shirakawa, K.T., Zhou, W., Oh, J., Otto, M., Fenical, W. and Gallo, R.L., 2018. A commensal strain of Staphylococcus epidermidis protects against skin neoplasia. Scientific Advances 4: eaao4502. https://doi.org/10.1126/sciadv.aao4502.
Nakatsuji, T., Hata, T.R., Tong, Y., Cheng, J.Y., Shafiq, F., Butcher, A.M., Salem, S.S., Brinton, S.L., Rudman Spergel, A.K., Johnson, K., Jepson, B., Calatroni, A., David, G., Ramirez-Gama, M., Taylor, P., Leung, D.Y.M. and Gallo, R.L., 2021. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nature Medicine 27: 700-709. https://doi.org/10.1038/s41591-021-01256-2
Nguyen, M.T., Uebele, J., Kumari, N., Nakayama, H., Peter, L., Ticha, O., Woischnig, A.K., Schmaler, M., Khanna, N., Dohmae, N., Lee, B.L., Bekeredjian-Ding, I. and Götz, F., 2017. Lipid moieties on lipoproteins of commensal and non-commensal staphylococci induce differential immune responses. Nature Communications 8: 2246. https://doi.org/10.1038/s41467-017-02234-4
Rendboe, A.K., Johannesen, T.B., Ingham, A.C., Månsson, E., Iversen, S., Baig, S., Edslev, S., Jensen, J.S., Söderquist, B., Andersen, P.S. and Stegger, M., 2020. The epidome – a species-specific approach to assess the population structure and heterogeneity of Staphylococcus epidermidis colonization and infection. BMC Microbiology 20: 362. https://doi.org/10.1186/s12866-020-02041-w
Sandiford, S. and Upton, M., 2012. Identification, characterization, and recombinant expression of epidermicin NI01, a novel unmodified bacteriocin produced by Staphylococcus epidermidis that displays potent activity against staphylococci. Antimicrobial Agents and Chemotherapy 56: 1539-1547. https://doi.org/10.1128/AAC.05397-11
Severn, M.M., Williams, M.R., Shahbandi, A., Bunch, Z.L., Lyon, L.M., Nguyen, A., Zaramela, L.S., Todd, D.A., Zengler, K., Cech, N.B., Gallo, R.L. and Horswill, A.R., 2022. The ubiquitous human skin commensal Staphylococcus hominis protects against opportunistic pathogens. mBio 13: e0093022. https://doi.org/10.1128/mbio.00930-22
Silverberg, J.I., Lio, P.A., Simpson, E.L., Li, C., Brownell, D.R., Gryllos, I., Ng-Cashin, J., Krueger, T., Swaidan, V.R., Bliss, R.L. and Kim, H.D., 2023. Efficacy and safety of topically applied therapeutic ammonia oxidising bacteria in adults with mild-to-moderate atopic dermatitis and moderate-to-severe pruritus: a randomised, double-blind, placebo-controlled, dose-ranging, phase 2b trial. EClinicalMedicine 60: 102002. https://doi.org/10.1016/j.eclinm.2023.102002
Stacy, A. and Belkaid, Y., 2019. Microbial guardians of skin health. Science 363: 227-228. https://doi.org/10.1126/science.aat4326
Torres Salazar, B.O., Dema, T., Schilling, N.A., Janek, D., Bornikoel, J., Berscheid, A., Elsherbini, A.M.A., Krauss, S., Jaag, S.J., Lämmerhofer, M., Li, M., Alqahtani, N., Horsburgh, M.J., Weber, T., Beltrán-Beleña, J.M., Brötz-Oesterhelt, H., Grond, S., Krismer, B. and Peschel, A., 2024. Commensal production of a broad-spectrum and short-lived antimicrobial peptide polyene eliminates nasal Staphylococcus aureus. Nature Microbiology 9: 200-213. https://doi.org/10.1038/s41564-023-01544-2
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 98: 411-424. https://doi.org/10.1007/s00253-013-5394-8
Zheng, Y., Hunt, R.L., Villaruz, A.E., Fisher, E.L., Liu, R., Liu, Q., Cheung, G.Y.C., Li, M. and Otto, M., 2022. Commensal Staphylococcus epidermidis contributes to skin barrier homeostasis by generating protective ceramides. Cell Host Microbe 30: 301-313. https://doi.org/10.1016/j.chom.2022.01.004
| 全部期间 | 过去一年 | 过去30天 | |
|---|---|---|---|
| 摘要浏览次数 | 327 | 327 | 327 |
| 全文浏览次数 | 24 | 24 | 24 |
| PDF下载次数 | 55 | 55 | 55 |
Topical probiotic formulations containing live bacteria are being explored as treatments for skin disorders such as atopic dermatitis and acne vulgaris. Certain bacterial strains with antimicrobial and/or anti-inflammatory properties show promise as bacterial therapeutics that could improve these conditions and serve as alternatives to antibiotics, which are increasingly compromised by rising antimicrobial resistance. However, little is known about the engraftment efficacy of such bacterial strains or their impact on the native skin microbiome. In this study, we applied two different coagulase-negative staphylococcal strains, one with antimicrobial activity (Staphylococcus epidermidis 2C-5) and one lacking any activity (Staphylococcus hominis H2-S92), on human back skin of 14 healthy volunteers. Engraftment was assessed using strain-specific PCR and three amplicon-based sequencing approaches at 7 and 30 days after application. Microbial profiles shifted modestly, showing a relative increase in staphylococci and a decrease in Cutibacterium spp. S. epidermidis 2C-5 drastically increased from 0.8% pre-application to 46.9% and 12.1% at days 7 and 30, respectively. S. hominis H2-S92 showed a relative rise from 1.4% to 35.8% at day 7, declining to 2.4% by day 30. Interestingly, Staphylococcus capitis relative abundance decreased by 50-60% at the application sites. These findings indicate that both strains can temporarily engraft and competitively displace native staphylococci. S. epidermidis 2C-5 appeared to colonize more effectively, possibly due to its bacteriocin production. Neither strain affected the phylotype composition of Cutibacterium acnes, suggesting lack of reach to sebaceous follicles, C. acnes’ primary niche. This study supports the potential of staphylococcal probiotics for modulating the skin microbiome. While they may be effective for conditions involving staphylococcal dysbiosis, such as atopic dermatitis, they appear less suited for treating disorders like acne vulgaris, which are associated with C. acnes imbalance.
| 全部期间 | 过去一年 | 过去30天 | |
|---|---|---|---|
| 摘要浏览次数 | 327 | 327 | 327 |
| 全文浏览次数 | 24 | 24 | 24 |
| PDF下载次数 | 55 | 55 | 55 |