Acne Pathogenesis

  • Gerd Plewig
  • Bodo Melnik
  • WenChieh Chen


Four major factors are involved in the pathogenesis of acne: (1) increased sebum production with altered lipid composition, (2) metagenomic modifications of the P. acnes microbiome favoring P. acnes biofilm, (3) deviated acroinfundibular keratinization leading to comedogenesis, and (4) inflammasome activation with infiltration of inflammatory cells into the perifollicular dermis. All four factors are interdependent. In our opinion quantitative and qualitative alterations of sebum represent the initial event driving all other related pathological features of acne.


  1. Agak GW, Qin M, Nobe J, et al. Propionibacterium acnes induces an IL-17 response in acne vulgaris that is regulated by vitamin A and vitamin D. J Invest Dermatol. 2014;134:366–73.CrossRefGoogle Scholar
  2. Agamia NF, Abdallah DM, S Sorour O, et al. Skin expression of mammalian target of rapamycin (mTOR), forkhead box transcription factorO1 (FoxO1) and serum insulin-like growth factor-1 (IGF-1) in patients with acne vulgaris and their relationship with diet. Br J Dermatol. 2016;174:1299–307.CrossRefGoogle Scholar
  3. Alexeyev OA, Jahns AC. Sampling and detection of skin Propionibacterium acnes: current status. Anaerobe. 2012;18:479–83.CrossRefGoogle Scholar
  4. Alimirah F, Panchanathan R, Chen J, et al. Expression of androgen receptor is negatively regulated by p53. Neoplasia. 2007;9:1152–9.CrossRefGoogle Scholar
  5. Bakan I, Laplante M. Connecting mTORC1 signaling to SREBP-1 activation. Curr Opin Lipidol. 2012;23:226–34.CrossRefGoogle Scholar
  6. Barnard E, Shi B, Kang D, et al. The balance of metagenomic elements shapes the skin microbiome in acne and health. Sci Rep. 2016;6:39491.CrossRefGoogle Scholar
  7. Bek-Thomsen M, Lomholt HB, Scavenius C, et al. Proteome analysis of human sebaceous follicle infundibula extracted from healthy and acne-affected skin. PLoS One. 2014;9:e107908.CrossRefGoogle Scholar
  8. 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;28:271–8.CrossRefGoogle Scholar
  9. Brüggemann H, Henne A, Hoster F, et al. The complete genome sequence of Propionibacterium acnes, a commensal of human skin. Science. 2004;305:671–3.CrossRefGoogle Scholar
  10. Burkhart CG, Burkhart CN. Expanding the microcomedone theory and acne therapeutics: Propionibacterium acnes biofilm produces biological glue that holds corneocytes together to form plug. J Am Acad Dermatol. 2007;57:722–4.CrossRefGoogle Scholar
  11. Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol. 2018;16:143–55.CrossRefGoogle Scholar
  12. Camera E, Ludovici M, Tortorella S, et al. Use of lipidomics to investigate sebum dysfunction in juvenile acne. J Lipid Res. 2016;57:1051–8.CrossRefGoogle Scholar
  13. Capitanio B, Lora V, Ludovici M, et al. Modulation of sebum oxidation and interleukin-1α levels associates with clinical improvement of mild comedonal acne. J Eur Acad Dermatol Venereol. 2014;28:1792–7.CrossRefGoogle Scholar
  14. Coenye T, Peeters E, Nelis HJ. Biofilm formation by Propionibacterium acnes is associated with increased resistance to antimicrobial agents and increased production of putative virulence factors. Res Microbiol. 2007;158:386–92.CrossRefGoogle Scholar
  15. Contassot E, French LE. New insights into acne pathogenesis: Propionibacterium acnes activates the inflammasome. J Invest Dermatol. 2014;134:310–3.CrossRefGoogle Scholar
  16. Deplewski D, Rosenfield RL. Growth hormone and insulin-like growth factors have different effects on sebaceous cell growth and differentiation. Endocrinology. 1999;140:4089–94.CrossRefGoogle Scholar
  17. Dozsa A, Dezso B, Toth BI, et al. PPARγ-mediated and arachidonic acid-dependent signaling is involved in differentiation and lipid production of human sebocytes. J Invest Dermatol. 2014;134:910–20.CrossRefGoogle Scholar
  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;32(Suppl 2):5–14.CrossRefGoogle Scholar
  19. Eady EA, Goodwin CE, Cove JH, et al. Inflammatory levels of interleukin 1 alpha are present in the majority of open comedones in acne vulgaris. Arch Dermatol. 1991;127:1238–9.CrossRefGoogle Scholar
  20. Feng Z. p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment. Cold Spring Harb Perspect Biol. 2010;2:a001057.CrossRefGoogle Scholar
  21. Fischer H, Fumicz J, Rossiter H, et al. Holocrine secretion of sebum is a unique DNase2-dependent mode of programmed cell death. J Invest Dermatol. 2017;137:587–94.CrossRefGoogle Scholar
  22. Fitz-Gibbon S, Tomida S, Chiu BH, et al. Propionibacterium acnes strain populations in the human skin microbiome associated with acne. J Invest Dermatol. 2013;133:2152–60.CrossRefGoogle Scholar
  23. Franz S, Simon JC, Saalbach A. Free fatty acids sensitize dendritic cells to amplify TH1/TH17-immune responses. Eur J Immunol. 2016;46:2043–53.CrossRefGoogle Scholar
  24. Gan Y, Zhou M, He C, et al. Lipidomics reveals skin surface lipid abnormity in male youth acne. Br J Dermatol. 2018;179:732–40.CrossRefGoogle Scholar
  25. Ganceviciene R, Böhm M, Fimmel S, Zouboulis CC. The role of neuropeptides in the multifactorial pathogenesis of acne vulgaris. Dermatoendocrinology. 2009;1:170–6.CrossRefGoogle Scholar
  26. Ge L, Gordon JS, Hsuan C, et al. Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity. J Invest Dermatol. 2003;120:707–14.CrossRefGoogle Scholar
  27. Guo JW, Lin TK, Wu CH, et al. Human sebum extract induces barrier disruption and cytokine expression in murine epidermis. J Dermatol Sci. 2015;78:34–43.CrossRefGoogle Scholar
  28. Hall JB, Cong Z, Imamura-Kawasawa Y, et al. Isolation and identification of the follicular microbiome: implications for acne research. J Invest Dermatol. 2018;138:2033–40.CrossRefGoogle Scholar
  29. Holland C, Mak TN, Zimny-Arndt U, et al. Proteomic identification of secreted proteins of Propionibacterium acnes. BMC Microbiol. 2010;10:230.CrossRefGoogle Scholar
  30. Isard O, Knol AC, Ariès MF, et al. Propionibacterium acnes activates the IGF-1/IGF-1R system in the epidermis and induces keratinocyte proliferation. J Invest Dermatol. 2011;131:59–66.CrossRefGoogle Scholar
  31. Jahns AC, Alexeyev OA. Three dimensional distribution of Propionibacterium acnes biofilms in human skin. Exp Dermatol. 2014;23:687–9.CrossRefGoogle Scholar
  32. Jahns AC, Lundskog B, Ganceviciene R, et al. An increased incidence of Propionibacterium acnes biofilms in acne vulgaris: a case-control study. Br J Dermatol. 2012;167:50–8.CrossRefGoogle Scholar
  33. Jahns AC, Eilers H, Ganceviciene R, Alexeyev OA. Propionibacterium species and follicular keratinocyte activation in acneic and normal skin. Br J Dermatol. 2015;172:981–7.CrossRefGoogle Scholar
  34. Jahns AC, Eilers H, Alexeyev OA. Transcriptomic analysis of Propionibacterium acnes biofilms in vitro. Anaerobe. 2016;42:111–8.CrossRefGoogle Scholar
  35. Janiczek-Dolphin N, Cook J, Thiboutot D, et al. Can sebum reduction predict acne outcome? Br J Dermatol. 2010;163:683–8.CrossRefGoogle Scholar
  36. Jasson F, Nagy I, Knol AC, et al. Different strains of Propionibacterium acnes modulate differently the cutaneous innate immunity. Exp Dermatol. 2013;22:587–92.CrossRefGoogle Scholar
  37. Ju Q, Tao T, Hu T, et al. Sex hormones and acne. Clin Dermatol. 2017;35:130–7.CrossRefGoogle Scholar
  38. Jugeau S, Tenaud I, Knol AC, et al. Induction of toll-like receptors by Propionibacterium acnes. Br J Dermatol. 2005;153:1105–13.CrossRefGoogle Scholar
  39. Kasimatis G, Fitz-Gibbon S, Tomida S, et al. Analysis of complete genomes of Propionibacterium acnes reveals a novel plasmid and increased pseudogenes in an acne associated strain. Biomed Res Int. 2013;2013:918320.CrossRefGoogle Scholar
  40. Katsuta Y, Iida T, Inomata S, Denda M. Unsaturated fatty acids induce calcium influx into keratinocytes and cause abnormal differentiation of epidermis. J Invest Dermatol. 2005;124:1008–13.CrossRefGoogle Scholar
  41. Kelhälä HL, Palatsi R, Fyhrquist N, et al. IL-17/Th17 pathway is activated in acne lesions. PLoS One. 2014;9:e105238.CrossRefGoogle Scholar
  42. Kim H, Moon SY, Sohn MY, Lee WJ. Insulin-like growth factor-1 increases the expression of inflammatory biomarkers and sebum production in cultured sebocytes. Ann Dermatol. 2017;29:20–5.CrossRefGoogle Scholar
  43. Kistowska M, Gehrke S, Jankovic D, et al. IL-1β drives inflammatory responses to propionibacterium acnes in vitro and in vivo. J Invest Dermatol. 2014;134:677–85.CrossRefGoogle Scholar
  44. Kligman AM, Wheatley VR, Mills OH. Comedogenicity of human sebum. Arch Dermatol. 1970;102:267–75.CrossRefGoogle Scholar
  45. Kwon HH, Yoon JY, Park SY, Suh DH. Analysis of distribution patterns of Propionibacterium acnes phylotypes and Peptostreptococcus species from acne lesions. Br J Dermatol. 2013;169:1152–5.CrossRefGoogle Scholar
  46. Li ZJ, Choi DK, Sohn KC, et al. Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes. J Invest Dermatol. 2014;134:2747–56.CrossRefGoogle Scholar
  47. Lomholt HB, Kilian M. Population genetic analysis of Propionibacterium acnes identifies a subpopulation and epidemic clones associated with acne. PLoS One. 2010;5:e12277.CrossRefGoogle Scholar
  48. Lomholt HB, Scholz CFP, Brüggemann H, et al. A comparative study of Cutibacterium (Propionibacterium) acnes clones from acne patients and healthy controls. Anaerobe. 2017;47:57–63.CrossRefGoogle Scholar
  49. Lwin SM, Kimber I, McFadden JP. Acne, quorum sensing and danger. Clin Exp Dermatol. 2014;39:162–7.CrossRefGoogle Scholar
  50. Mattii M, Lovászi M, Garzorz N, et al. Sebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells. Br J Dermatol. 2018;178:722–30.CrossRefGoogle Scholar
  51. McDowell A. Over a decade of recA and tly gene sequence typing of the skin bacterium Propionibacterium acnes: What have we learnt? Microorganisms. 2017;6:E1.CrossRefGoogle Scholar
  52. McNairn AJ, Doucet Y, Demaude J, et al. TGFβ signaling regulates lipogenesis in human sebaceous glands cells. BMC Dermatol. 2013;13:2.CrossRefGoogle Scholar
  53. Melnik BC. Acne vulgaris: an inflammasomopathy of the sebaceous follicle induced by deviated FoxO1/mTORC1 signalling. Br J Dermatol. 2016;174:1186–8.CrossRefGoogle Scholar
  54. Melnik BC. p53: key conductor of all anti-acne therapies. J Transl Med. 2017;15:195.CrossRefGoogle Scholar
  55. Melnik BC. Acne vulgaris: the metabolic syndrome of the pilosebaceous follicle. Clin Dermatol. 2018;36:29–40.CrossRefGoogle Scholar
  56. Melnik BC, Schmitz G. Role of insulin, insulin-like growth factor-1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris. Exp Dermatol. 2009;18:833–41.CrossRefGoogle Scholar
  57. Mills OH, Porte M, Kligman AM. Enhancement of comedogenic substances by ultraviolet radiation. Br J Dermatol. 1978;98:145–50.CrossRefGoogle Scholar
  58. Mirdamadi Y, Thielitz A, Wiede A, et al. Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro. Mol Cell Endocrinol. 2015;415:32–44.CrossRefGoogle Scholar
  59. Monfrecola G, Lembo S, Caiazzo G, et al. Mechanistic target of rapamycin (mTOR) expression is increased in acne patients’ skin. Exp Dermatol. 2016;25:153–5.CrossRefGoogle Scholar
  60. Navarini AA, Simpson MA, Weale M, et al. Genome-wide association study identifies three novel susceptibility loci for severe acne vulgaris. Nat Commun. 2014;5:4020.PubMedGoogle Scholar
  61. Ottaviani M, Camera E, Picardo M. Lipid mediators in acne. Mediators Inflamm. 2010;2010:858176.CrossRefGoogle Scholar
  62. Pappas A, Anthonavage M, Gordon JS. Metabolic fate and selective utilization of major fatty acids in human sebaceous gland. J Invest Dermatol. 2002;118:164–71.CrossRefGoogle Scholar
  63. Perisho K, Wertz PW, Madison KC, et al. Fatty acids of acylceramides from comedones and from the skin surface of acne patients and control subjects. J Invest Dermatol. 1988;90:350–3.CrossRefGoogle Scholar
  64. Plewig G, Fulton JE, Kligman AM. Cellular dynamics of comedo formation in acne vulgaris. Arch Dermatol Forsch. 1971;242:12–29.CrossRefGoogle Scholar
  65. Powell EW, Beveridge GW. Sebum excretion and sebum composition in adolescent men with and without acne vulgaris. Br J Dermatol. 1970;82:243–9.CrossRefGoogle Scholar
  66. Qin M, Pirouz A, Kim MH, Krutzik SR, et al. Propionibacterium acnes induces IL-1β secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol. 2014;134:381–8.CrossRefGoogle Scholar
  67. Schneider MR, Paus R. Sebocytes, multifaceted epithelial cells: lipid production and holocrine secretion. Int J Biochem Cell Biol. 2010;42:181–5.CrossRefGoogle Scholar
  68. Scholz CF, Kilian M. The natural history of cutaneous propionibacteria, and reclassification of selected species within the genus Propionibacterium to the proposed novel genera Acidipropionibacterium gen. nov., Cutibacterium gen. nov. and Pseudopropionibacterium gen. nov. Int J Syst Evol Microbiol. 2016;66:4422–32.CrossRefGoogle Scholar
  69. Seleit I, Bakry OA, Abdou AG, Hashim A. Body mass index, selected dietary factors, and acne severity: are they related to in situ expression of insulin-like growth factor-1? Anal Quant Cytopathol Histpathol. 2014;36:267–78.PubMedGoogle Scholar
  70. Selway JL, Kurczab T, Kealey T, Langlands K. Toll-like receptor 2 activation and comedogenesis: implications for the pathogenesis of acne. BMC Dermatol. 2013;13:10.CrossRefGoogle Scholar
  71. Smith TM, Gilliland K, Clawson GA, Thiboutot D. IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. J Invest Dermatol. 2008;128:1286–93.CrossRefGoogle Scholar
  72. Stelzner K, Herbert D, Popkova Y, et al. Inflammasome activation by Propionibacterium acnes: the story of IL-1 in acne continues to unfold. J Invest Dermatol. 2014;134:595–7.CrossRefGoogle Scholar
  73. Stewart ME, Grahek MO, Cambier LS, et al. Dilutional effect of increased sebaceous gland activity on the proportion of linoleic acid in sebaceous wax esters and in epidermal acylceramides. J Invest Dermatol. 1986;87:733–6.CrossRefGoogle Scholar
  74. Tomida S, Nguyen L, Chiu BH, et al. Pan-genome and comparative genome analyses of propionibacterium acnes reveal its genomic diversity in the healthy and diseased human skin microbiome. MBio. 2013;4:e00003–13.CrossRefGoogle Scholar
  75. Wang Y, Kuo S, Shu M, et al. Staphylococcus epidermidis in the human skin microbiome mediates fermentation to inhibit the growth of Propionibacterium acnes: implications of probiotics in acne vulgaris. Appl Microbiol Biotechnol. 2014;98:411–24.CrossRefGoogle Scholar
  76. Zhou BR, Zhang JA, Zhang Q, et al. Palmitic acid induces production of proinflammatory cytokines interleukin-6, interleukin-1β, and tumor necrosis factor-α via a NF-κB-dependent mechanism in HaCaT keratinocytes. Mediators Inflamm. 2013;2013:530429.PubMedPubMedCentralGoogle Scholar
  77. Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol. 2014;28:527–32.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Gerd Plewig
    • 1
  • Bodo Melnik
    • 2
  • WenChieh Chen
    • 3
  1. 1.Department of Dermatology and AllergyLudwig-Maximilian-University MunichMunichGermany
  2. 2.Department of Dermatology, Environmental Medicine and Health TheoryUniversity of OsnabrückOsnabrückGermany
  3. 3.Department of Dermatology and AllergyTechnical University of MunichMunichGermany

Personalised recommendations