Acne: role of Cutibacterium acnes and possibilities of using bacteriophages

Abstract

BACKGROUND: The role of Cutibacterium acnes in the pathogenesis of acne vulgaris and its adverse effect on follicular hyperkeratosis, inflammation and the skin microbiome have now been established. Their excessive colonization contributes to the loss of microbial diversity of the skin, activates the innate immune system, leads to the appearance of skin rash elements and chronic inflammation. Bacteriophages are considered as a new promising direction in the treatment of patients with acne, as they have an antimicrobial effect against C. acnes; contribute to the preservation of the skin microbiome; have an indirect effect on the innate and adaptive immune response.

AIM: To evaluate the effectiveness and safety of topical therapy with cosmetic gel with bacteriophages Fagoderm in the complex treatment of patients with moderate to severe acne.

MATERIALS AND METHODS: In the design of a simple open prospective study in parallel groups, the effect of cosmetic gel with bacteriophages on the number of comedones, pupules and pustules was assessed in 35 adult patients with moderate acne. During therapy, possible adverse events were simultaneously recorded.

RESULTS: During therapy, similar dynamics were noted in the form of a decrease in non-inflammatory elements of acne both in the group of people receiving a combination of adapalene and phagoderm, and in the comparison group, where monotherapy with adapalene was carried out. The number of inflammatory elements of acne decreased in both groups, but in the main group this happened at an earlier time. Compared to the initial data, already in the 2nd week the number of inflammatory elements decreased by 50% (in comparison ― by 32%); by the end of the 4th ― by 95% (respectively in the comparison group ― by 74%).

CONCLUSION: Cosmetic gel with bacteriophages with bacteriophages helps reduce the inflammatory manifestations of moderate acne.

Keywords

acne vulgaris / Cutibacterium acnes / therapy / bacteriophages / cosmetic gel with bacteriophages

References

[1] Zouboulis CC, Bettoli V. Management of severe acne. Br J Dermatol. 2015;172(S1):27–36. doi: 10.1111/bjd.13639

[2] Zouboulis C.C., Bettoli V. Management of severe acne // Br J Dermatol. 2015. Vol. 172, N S1. P. 27–36. doi: 10.1111/bjd.13639

[3] Dréno B. What is new in the pathophysiology of acne, an overview. J Eur Acad Dermatol Venereol. 2017;31:8–12. doi: 10.1111/jdv.14374

[4] Dréno B. What is new in the pathophysiology of acne, an overview // J Eur Acad Dermatol Venereol. 2017. Vol. 31. P. 8–12. doi: 10.1111/jdv.14374

[5] Antiga E, Verdelli A, Bonciani D, et al. Acne: A new model of immune-mediated chronic inflammatory skin disease. G Ital Dermatol Venereol. 2015;150(2):247–254.

[6] Antiga E., Verdelli A., Bonciani D., et al. Acne: A new model of immune-mediated chronic inflammatory skin disease // G Ital Dermatol Venereol. 2015. Vol. 150, N 2. P. 247–254.

[7] Gollnick HP, Bettoli V, Lambert J, et al. A consensus-based practical and daily guide for the treatment of acne patients. J Eur Acad Dermatol Venereol. 2016;30(9):1480–1490. doi: 10.1111/jdv.13675

[8] Gollnick H.P., Bettoli V., Lambert J., et al. A consensus-based practical and daily guide for the treatment of acne patients // J Eur Acad Dermatol Venereol. 2016. Vol. 30, N 9. P. 1480–1490. doi: 10.1111/jdv.13675

[9] Bhat YJ, Latief I, Hassan I. Update on etiopathogenesis and treatment of acne. Indian J Dermatol Venereol Leprology. 2017;83(3):298. doi: 10.4103/0378-6323.199581

[10] Bhat Y.J., Latief I., Hassan I. Update on etiopathogenesis and treatment of acne // Indian J Dermatol Venereol Leprology. 2017. Vol. 83, N 3. P. 298. doi: 10.4103/0378-6323.199581

[11] O’Neill AM, Gallo RL. Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris. Microbiome. 2018;6:177. doi: 10.1186/s40168-018-0558-5

[12] O’Neill A.M., Gallo R.L. Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris // Microbiome. 2018. Vol. 6. P. 177. doi: 10.1186/s40168-018-0558-5

[13] Wang D, Duncan B, Li X, Shi J. The role of NLRP3 inflammasome in infection-related, immune-mediated and autoimmune skin diseases. J Dermatological Sci. 2020;98(3):146–151.

[14] Wang D., Duncan B., Li X., Shi J. The role of NLRP3 inflammasome in infection-related, immune-mediated and autoimmune skin diseases // J Dermatological Sci. 2020. Vol. 98, N 3. P. 146–151.

[15] Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi: 10.12688/f1000research.15659.1

[16] Platsidaki E., Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne // F1000Res. 2018. Vol. 7. P. F1000 Faculty Rev-1953. doi: 10.12688/f1000research.15659.1

[17] Dréno B, Pécastaings S, Corvec S, et al. Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: A brief look at the latest updates. J Eur Acad Dermatol Venereol. 2018;32:5–14. doi: 10.1111/jdv.15043

[18] Dréno B., Pécastaings S., Corvec S., et al. Cutibacterium acnes (Propionibacterium acnes) and acne vulgaris: A brief look at the latest updates // J Eur Acad Dermatol Venereol. 2018. Vol. 32. P. 5–14. doi: 10.1111/jdv.15043

[19] Del Rosso JQ, Kircik LH. The sequence of inflammation, relevant biomarkers, and the pathogenesis of acne vulgaris: What does recent research show and what does it mean to the clinician? J Drugs Dermatol. 2013;12(8, Suppl):s109–115.

[20] Del Rosso J.Q., Kircik L.H. The sequence of inflammation, relevant biomarkers, and the pathogenesis of acne vulgaris: What does recent research show and what does it mean to the clinician? // J Drugs Dermatol. 2013. Vol. 12, N 8, Suppl. P. s109–115.

[21] Dreno B, Dekio I, Baldwin H, et al. Acne microbiome: From phyla to phylotypes. J Eur Acad Dermatol Venereol. 2024;38(4):657–664. doi: 10.1111/jdv.19540

[22] Dreno B., Dekio I., Baldwin H., et al. Acne microbiome: From phyla to phylotypes // J Eur Acad Dermatol Venereol. 2024. Vol. 38, N 4. P. 657–664. doi: 10.1111/jdv.19540

[23] Dagnelie MA, Corvec S, Saint-Jean M, et al. Cutibacterium acnes phylotypes diversity loss: A trigger for skin inflammatory process. J Eur Acad Dermatol Venereol. 2019;33(12):2340–2348. doi: 10.1111/jdv.15795

[24] Dagnelie M.A., Corvec S., Saint-Jean M., et al. Cutibacterium acnes phylotypes diversity loss: A trigger for skin inflammatory process // J Eur Acad Dermatol Venereol. 2019. Vol. 33, N 12. P. 2340–2348. doi: 10.1111/jdv.15795

[25] Dagnelie MA, Khammari A, Dréno B, Corvec S. Cutibacterium acnes molecular typing: time to standardize the method. Clin Microbiol Infection. 2018;24(11):1149–1155. doi: 10.1016/j.cmi.2018.03.010

[26] Dagnelie M.A., Khammari A., Dréno B., Corvec S. Cutibacterium acnes molecular typing: Time to standardize the method // Clin Microbiol Infection. 2018. Vol. 24, N 11. P. 1149–1155. doi: 10.1016/j.cmi.2018.03.010

[27] Beylot C, Auffret N, Poli F, et al. Propionibacterium acnes: An update on its role in the pathogenesis of acne. J Eur Acad Dermatol Venereol. 2014;28(3):271–278. doi: 10.1111/jdv.12224

[28] Beylot C., Auffret N., Poli F., et al. Propionibacterium acnes: An update on its role in the pathogenesis of acne // J Eur Acad Dermatol Venereol. 2014. Vol. 28, N 3. P. 271–278. doi: 10.1111/jdv.12224

[29] Cong TX, Hao D, Wen X, et al. From pathogenesis of acne vulgaris to anti-acne agents. Arch Dermatological Res. 2019;311(5):337–349. doi: 10.1007/s00403-019-01908-x

[30] Cong T.X., Hao D., Wen X., et al. From pathogenesis of acne vulgaris to anti-acne agents // Arch Dermatological Res. 2019. Vol. 311, N 5. P. 337–349. doi: 10.1007/s00403-019-01908-x

[31] Farrah G, Tan E. The use of oral antibiotics in treating acne vulgaris: A new approach. Dermatologic Ther. 2016;29(5):377–384.

[32] Farrah G., Tan E. The use of oral antibiotics in treating acne vulgaris: A new approach // Dermatologic Ther. 2016. Vol. 29, N 5. P. 377–384.

[33] Oudenhoven MD, Kinney MA, McShane DB, et al. Adverse effects of acne medications: Recognition and management. Am J Clin Dermatol. 2015;16(4):231–242. doi: 10.1007/s40257-015-0127-7

[34] Oudenhoven M.D., Kinney M.A., McShane D.B., et al. Adverse effects of acne medications: Recognition and management // Am J Clin Dermatol. 2015. Vol. 16, N 4. P. 231–242. doi: 10.1007/s40257-015-0127-7

[35] Liu PF, Hsieh YD, Lin YC, et al. Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris. Curr Drug Metabolism. 2015;16(4):245–254. doi: 10.2174/1389200216666150812124801

[36] Liu P.F., Hsieh Y.D., Lin Y.C., et al. Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris // Curr Drug Metabolism. 2015. Vol. 16, N 4. P. 245–254. doi: 10.2174/1389200216666150812124801

[37] Karadag AS, Aslan Kayiran M, Wu CY, et al. Antibiotic resistance in acne: Changes, consequences and concerns. J Eur Acad Dermatol Venereol. 2020;35(1):73–78. doi: 10.1111/jdv.16686

[38] Karadag A.S., Aslan Kayiran M., Wu C.Y., et al. Antibiotic resistance in acne: Changes, consequences and concerns // J Eur Acad Dermatol Venereol. 2020. Vol. 35, N 1. P. 73–78. doi: 10.1111/jdv.16686

[39] Woo TE, Sibley CD. The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis. J Am Acad Dermatol. 2020;82(1):222–228. doi: 10.1016/j.jaad.2019.08.078

[40] Woo T.E., Sibley C.D. The emerging utility of the cutaneous microbiome in the treatment of acne and atopic dermatitis // J Am Acad Dermatol. 2020. Vol. 82, N 1. P. 222–228. doi: 10.1016/j.jaad.2019.08.078

[41] Roach DR, Leung CY, Henry M, et al. Synergy between the host immune system and bacteriophage is essential for successful phage therapy against an acute respiratory pathogen. Cell Host Microbe. 2017;22(1):38–47.e4. doi: 10.1016/j.chom.2017.06.018

[42] Roach D.R., Leung C.Y., Henry M., et al. Synergy between the host immune system and bacteriophage is essential for successful phage therapy against an acute respiratory pathogen // Cell Host Microbe. 2017. Vol. 22, N 1. P. 38–47.e4. doi: 10.1016/j.chom.2017.06.018

[43] Ilyina TS, Tolordava ER, Romanova YM. A look at phage therapy one hundred years after the bacteriophages discovery. Molecular Genetics, Microbiology and Virology. 2019;37(3):103–112. EDN: FWJUFO doi: 10.17116/molgen201937031103

[44] Ильина Т.С., Толордава Э.Р., Романова Ю.М. Взгляд на фаготерапию через 100 лет после открытия бактериофагов // Молекулярная генетика, микробиология и вирусология. 2019. Т. 37, № 3. С. 103–112. EDN: FWJUFO doi: 10.17116/molgen201937031103

[45] Parasion S, Kwiatek M, Gryko R, et al. Bacteriophages as an alternative strategy for fighting biofilm development. Polish J Microbiol. 2014;63(2):137–145.

[46] Parasion S., Kwiatek M., Gryko R., et al. Bacteriophages as an alternative strategy for fighting biofilm development // Polish J Microbiol. 2014. Vol. 63, N 2. P. 137–145.

[47] Hanlon GW. Bacteriophages: An appraisal of their role in the treatment of bacterial infections. Int J Antimicrob Agents. 2007;30(2):118–128. doi: 10.1016/j.ijantimicag.2007.04.006

[48] Hanlon G.W. Bacteriophages: An appraisal of their role in the treatment of bacterial infections // Int J Antimicrob Agents. 2007. Vol. 30, N 2. P. 118–128. doi: 10.1016/j.ijantimicag.2007.04.006

[49] Jariah RO, Hakim MS. Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy. Rev Med Virol. 2019;29(5):e2055. doi: 10.1002/rmv.2055

[50] Jariah R.O., Hakim M.S. Interaction of phages, bacteria, and the human immune system: Evolutionary changes in phage therapy // Rev Med Virol. 2019. Vol. 29, N 5. P. e2055. doi: 10.1002/rmv.2055

[51] Leung CY, Weitz JS. Modeling the synergistic elimination of bacteria by phage and the innate immune system. J Theor Biol. 2017;429:241–252. doi: 10.1016/j.jtbi.2017.06.037

[52] Leung C.Y., Weitz J.S. Modeling the synergistic elimination of bacteria by phage and the innate immune system // J Theor Biol. 2017. Vol. 429. P. 241–252. doi: 10.1016/j.jtbi.2017.06.037

[53] Lenneman BR, Fernbach J, Loessner MJ, et al. Enhancing phage therapy through synthetic biology and genome engineering. Curr Opin Biotechnol. 2021;68:151–159. doi: 10.1016/j.copbio.2020.11.003

[54] Lenneman B.R., Fernbach J., Loessner M.J., et al. Enhancing phage therapy through synthetic biology and genome engineering // Curr Opin Biotechnol. 2021. Vol. 68. P. 151–159. doi: 10.1016/j.copbio.2020.11.003

[55] Oechslin F. Resistance development to bacteriophages occurring during bacteriophage therapy. Viruses. 2018;10(7):351. doi: 10.3390/v10070351

[56] Oechslin F. Resistance development to bacteriophages occurring during bacteriophage therapy // Viruses. 2018. Vol. 10, N 7. P. 351. doi: 10.3390/v10070351

[57] Kebriaei R, Lev KL, Shah RM, et al. Eradication of biofilm-mediated methicillin-resistant Staphylococcus aureus infections in vitro: Bacteriophage antibiotic combination. Microbiol Spectr. 2022;10(2):e0041122. doi: 10.1128/spectrum.00411-22

[58] Kebriaei R., Lev K.L., Shah R.M., et al. Eradication of biofilm-mediated methicillin-resistant Staphylococcus aureus infections in vitro: Bacteriophage antibiotic combination // Microbiol Spectr. 2022. Vol. 10, N 2. P. e0041122. doi: 10.1128/spectrum.00411-22

[59] Brown TL, Petrovski S, Dyson ZA, et al. The formulation of bacteriophage in a semi solid preparation for control of propionibacterium acnes growth. PLoS One. 2016;11(3):e0151184. doi: 10.1371/journal.pone.0151184

[60] Brown T.L., Petrovski S., Dyson Z.A., et al. The formulation of bacteriophage in a semi solid preparation for control of propionibacterium acnes growth // PLoS One. 2016. Vol. 11, N 3. P. e0151184. doi: 10.1371/journal.pone.0151184

[61] Kim MJ, Eun DH, Kim SM, et al. Efficacy of bacteriophages in propionibacterium acnes-induced inflammation in mice. Ann Dermatol. 2019;31(1):22–28. doi: 10.5021/ad.2019.31.1.22

[62] Kim M.J., Eun D.H., Kim S.M., et al. Efficacy of bacteriophages in propionibacterium acnes-induced inflammation in mice // Ann Dermatol. 2019. Vol. 31, N 1. P. 22–28. doi: 10.5021/ad.2019.31.1.22

[63] Zurabov AYu, Zhilenkov EL, Popov DV, et al. Phagoderm phage preparation and its application perspectives in dermatology and cosmetology. Vestnik esteticheskoi meditsiny. 2012;11(3):56–63. EDN: PFQKCB

[64] Зурабов А.Ю., Жиленков Е.Л., Попов Д.В., и др. Фаговый препарат «Фагодерм» и перспективы его использования в дерматологии и косметологии // Вестник эстетической медицины. 2012. Т. 11, № 3. С. 56–63. EDN: PFQKCB

[65] Zhukova OV, Kasikhina EI, Ostretsova MN, Nemer A. Bacteriophages in the treatment and prevention of atopic dermatitis and dermatoses complicated by secondary bacterial infection. Medical Council. 2022;(13):66–72. EDN: LIHXKN doi: 10.21518/2079-701X-2022-16-13-66-72

[66] Жукова О.В., Касихина Е.И., Острецова М.Н., Немер А. Бактериофаги в терапии и профилактике атопического дерматита и дерматозов, осложненных вторичной бактериальной инфекцией // Медицинский совет. 2022. Т. 16, № 13. С. 66–72. EDN: LIHXKN doi: 10.21518/2079-701X-2022-16-13-66-72

[67] Clinical recommendations. Acne. Moscow; 2016. Available from: https://library.mededtech.ru/rest/documents/cr_721/. Accessed: 15.04.2024.

[68] Клинические рекомендации Минздрава России. Акне. Москва, 2016. Режим доступа: https://library.mededtech.ru/rest/documents/cr_721/. Дата обращения: 15.04.2024.

RIGHTS & PERMISSIONS

Eco-Vector