Revisiting Acne Pathogenesis: Unmasking Malassezia as a Fundamental Driver in All Forms of Acne

by f.c., Malezia

Abstract

Acne vulgaris has historically been framed as a bacterial-driven disorder, primarily attributed to the overgrowth of Cutibacterium acnes (formerly Propionibacterium acnes). However, emerging microbiome research challenges this model by revealing the critical participation of Malassezia yeasts. Studies employing PCR sequencing, follicular content analyses, and metagenomic profiling consistently detect Malassezia—particularly M. globosa and M. restricta—alongside C. acnes in both comedones and inflammatory lesions. Mechanistic findings highlight Malassezia’s potent lipase activity, its interaction with Toll-like receptor 2 (TLR2), and its ability to generate pro-inflammatory mediators, all of which can initiate or exacerbate early comedone formation. Moreover, multiple investigations confirm that standard antibacterial regimens alone fail to address the fungal component, often resulting in recalcitrant or relapsing acne. This review synthesizes data positioning Malassezia as a key player in acne pathogenesis, challenges the outdated notion that acne is purely bacterial, and advocates for a microbiome-based perspective in understanding and treating all forms of acne. Failure to account for Malassezia in acne management may compromise therapeutic outcomes—a position we at Malezia have argued for years, despite persistent skepticism.

Introduction

Acne vulgaris remains one of the most prevalent dermatological conditions, characterized by non-inflammatory (comedonal) and inflammatory (papules, pustules) lesions on sebaceous skin [1]. Traditional dogma centers on Cutibacterium acnes, hyperkeratinization, sebum overproduction, and local inflammation as the four primary drivers of acne [2]. Although C. acnes has long been viewed as acne’s main microbiological culprit, recent dermatological investigations underscore the complexity of the skin microbiome. Next-generation sequencing (NGS) and PCR-based analyses have broadened our scope to include other microorganisms, such as Staphylococcus epidermidis and fungal species in the genus Malassezia [3,4].

Despite the growing recognition of Malassezia as an abundant commensal fungus capable of exacerbating cutaneous inflammation, its role in acne has historically been relegated to “fungal acne” or “Malassezia folliculitis.” This oversimplifies the organism’s contribution and overlooks compelling evidence of Malassezia involvement in classical acne vulgaris [5,6].

This article will present the mounting data that Malassezia—via potent lipase activity, synergy with C. acnes, and direct immunomodulation—drives acne pathogenesis alongside or, in certain contexts, more fundamentally than bacteria. We will reconcile seemingly conflicting reports on Malassezia abundance in acne, evaluate mechanistic research on how the fungus triggers comedogenesis, and explore how ignoring Malassezia can undermine standard acne therapies.

The Role of Malassezia in Acne Pathogenesis

Microbial Findings from PCR Sequencing and Follicular Analyses

Recent metagenomic studies confirm that the microbial community in acne is not exclusively bacterial. Instead, Malassezia emerges as a consistent occupant of inflammatory acne lesions [3,4,7]. In a pivotal study by Akaza et al., researchers collected comedone and pustule contents and detected large populations of C. acnes, Staphylococcus spp. (especially S. epidermidis), and Malassezia spp. in the same follicular microenvironment [6].

A 2022 investigation employing deep sequencing similarly found that while Cutibacterium remains a major component, Malassezia restricta and Malassezia globosa are ubiquitous in both superficial and deep acne lesions [3]. Further, Tsubuku et al. analyzed pustules from facial acne, discovering robust Malassezia colonization—even when C. acnes was absent [8].

These data are not always reflected in older culture-based research, which often underreport Malassezia due to difficulties in growing the yeast on standard media. By contrast, PCR and next-generation sequencing bypass the need for specialized culture, revealing that Malassezia is indeed widespread in inflamed acne lesions [5–7].

Mechanistic Evidence: Lipase Activity, TLR2 Activation, and Sebum Breakdown

A key pathological mechanism involves Malassezia’s strong lipolytic (lipase) capacity—estimated to be far more potent than that of C. acnes [2]. By hydrolyzing triglycerides in sebum to free fatty acids (FFAs), Malassezia alters the follicular milieu, leading to:

  1. Comedo Initiation: Accumulation of FFAs can trigger hyperkeratinization in the infundibulum, blocking the follicle’s exit. This parallels the classic model attributing comedo formation solely to C. acnes, but now with an important fungal contribution [1,5].
  2. Intense Inflammation: Malassezia’s cell wall, rich in glycans and lipids, is recognized by innate immune receptors such as Toll-like receptor 2 (TLR2). This interaction promotes the release of IL-8 and other proinflammatory cytokines from keratinocytes and monocytes, thus amplifying neutrophilic infiltration and driving the visible inflammation in acne [2,5,9]. Zhang et al. (2024) further emphasize that Malassezia, through its high lipase activity and cell‐wall components, can stimulate dendritic cells to release IL‐12 and IL‐23—cytokines known to drive Th17 polarization—which supports our model in which Malassezia acts as a central inflammatory mediator in acne. [10]
  3. Microbiome Cross-talk: Fungal–bacterial synergy is possible. In certain microenvironments, Malassezia and C. acnes co-colonize and may collectively intensify inflammation. Alternatively, antibiotic therapy directed against C. acnes can inadvertently favor fungal overgrowth by eliminating competing bacteria [1,4].

Comparing Malassezia to the Old Bacterial Model

While C. acnes remains a proven factor in acne, the conventional single-organism model faces mounting challenges:

  • Stubborn or Worsening Acne on Antibiotics: Dermatologists commonly observe patients whose “acne” flares during antibiotic therapy, consistent with Malassezia flourishing in the absence of bacterial competitors [1,5].
  • Absence of C. acnes in Some Lesions: Tsubuku et al. identified pustules with minimal C. acnes but high Malassezia loads, which belies the assumption that C. acnes is always the primary driver [8].
  • Potent Lipase: The high lipase activity of Malassezia rivals or exceeds that of C. acnes, suggesting it may form or exacerbate comedones faster than the bacterium can [2,6].
  • Neutral or Low C. acnes Antibody Titers: Some persistent adult acne patients do not exhibit elevated anti-C. acnes antibodies, indicating other immunogenic factors (e.g. Malassezia) could be fueling their inflammation [5].

These findings support a microbiome-centric model in which Malassezia plays a primary role—rather than being a minor, incidental presence. Unlike the traditional view that primarily implicates Cutibacterium acnes, recent reviews underscore that Malassezia’s immunomodulatory effects, including its induction of pro‐inflammatory cytokines, demand that we consider a more integrated microbial paradigm for acne. [10]

Debunking the ‘Fungal vs. Bacterial Acne’ Dichotomy

While “fungal acne” typically references Malassezia folliculitis, Malassezia also plays a crucial role in conventional acne vulgaris:

  1. Overlap in Follicular Colonization: Studies show that Cutibacterium, Staphylococcus, and Malassezia frequently coexist in the same follicles [3,6]. The notion that Malassezia belongs only in “fungal acne” and C. acnes in “bacterial acne” is simplistic and overlooks the synergy or competition among microbes.
  2. Mixed Lesions: Histopathology and PCR analyses of acne papules commonly find both C. acnes and Malassezia, though not always at the same proportions. Subsets of acne may have a larger fungal component, explaining partial or no response to antibiotic monotherapy [5,8].
  3. Microbiome Disorder: Acne is better framed as a dysbiosis, wherein multiple microorganisms—bacteria and fungi—exploit the hypersebaceous, plugged follicle to incite inflammation. Whether C. acnes or Malassezia predominates may vary with sebum composition, antibiotic use, climate, and individual immune factors [1,2].

Implications for Skincare & Treatment

Why Conventional Antibiotic-Only Regimens May Fail

Targeting C. acnes alone leaves the fungal component unaddressed. Patients with significant Malassezia colonization may see minimal improvement or even deterioration under antibiotic therapy [1,4]. This mismatch is especially evident in “recalcitrant acne” cases that do not respond to standard antibacterial regimens.

Interestingly, Maître et al. (2024) found that while early acne is marked by significant bacterial dysbiosis, the fungal community—dominated by Malassezia—remains relatively stable. This suggests that Malassezia may provide a primed background upon which shifts in the bacterial community can unmask its pro‐inflammatory potential. [11]

The Need to Formulate with Malassezia in Mind

Skincare products often use fatty acids (C12–C24 range) that can feed Malassezia, inadvertently fueling breakouts. Instead, focusing on non-comedogenic, “Malassezia-safe” ingredients—like medium-chain triglycerides (C8–C10) and inert silicones—helps avoid feeding the fungus [5]. Meanwhile, active ingredients with broad antimicrobial spectra, such as benzoyl peroxide, effectively reduce both C. acnes and Malassezia populations, which clarifies why it often outperforms purely antibacterial or retinoid-based treatments in practice [9].

Microbiome-Focused Future

Emerging therapies that specifically target or modulate the entire skin microbiome—bacteriophages for C. acnes, antifungals for Malassezia, or probiotic supernatants—are promising [4,9].

By restoring balanced microbial communities, these approaches might achieve better and more sustained clearance than monotherapies that ignore the fungal dimension. The lesson is that ignoring Malassezia can leave a major piece of acne pathogenesis unaddressed.

Conclusion

A growing body of literature firmly positions Malassezia at the heart of acne pathogenesis—akin to C. acnes, not just in the separate domain of “fungal acne.” This reconceptualization is supported by:

  • PCR and metagenomic analyses revealing Malassezia in comedones and inflammatory lesions.
  • Mechanistic data on its potent lipase-driven free fatty acid production, TLR2 activation, and synergy with C. acnes.
  • Clinical reports of recalcitrant acne responding only when antifungal therapy is introduced.

Going forward, we must adopt a microbiome-based lens that acknowledges Malassezia as a fundamental acne driver. Skincare formulations ignoring its presence risk fueling breakouts. Meanwhile, multi-target regimens that curb C. acnes and Malassezia are already showing superior, lasting results. Indeed, at Malezia, we have argued for years that Malassezia’s presence is central across all forms of acne—and it is time the field caught up.

References:

  1. Rubenstein RM, Malerich SA. Malassezia (pityrosporum) folliculitis. J Clin Aesthet Dermatol. 2014 Mar;7(3):37-41. PMID: 24688625; PMCID: PMC3970831.
  2. Lee YB, Byun EJ, Kim HS. Potential Role of the Microbiome in Acne: A Comprehensive Review. J Clin Med. 2019 Jul 7;8(7):987. doi: 10.3390/jcm8070987. PMID: 31284694; PMCID: PMC6678709.
  3. Akaza N, Takasaki K, Nishiyama E, Usui A, Miura S, Yokoi A, Futamura K, Suzuki K, Yashiro Y, Yagami A. The Microbiome in Comedonal Contents of Inflammatory Acne Vulgaris is Composed of an Overgrowth of Cutibacterium Spp. and Other Cutaneous Microorganisms. Clin Cosmet Investig Dermatol. 2022 Sep 21;15:2003-2012. doi: 10.2147/CCID.S379609. PMID: 36172249; PMCID: PMC9510696.
  4. Guo Z, Yang Y, Wu Q, Liu M, Zhou L, Zhang L, Dong D. New insights into the characteristic skin microorganisms in different grades of acne and different acne sites. Front Microbiol. 2023 Apr 27;14:1167923. doi: 10.3389/fmicb.2023.1167923. PMID: 37180251; PMCID: PMC10172595.
  5. Xu H, Li H. Acne, the Skin Microbiome, and Antibiotic Treatment. Am J Clin Dermatol. 2019 Jun;20(3):335-344. doi: 10.1007/s40257-018-00417-3. PMID: 30632097; PMCID: PMC6534434.
  6. Akaza N, Akamatsu H, Numata S, Yamada S, Yagami A, Nakata S, Matsunaga K. Microorganisms inhabiting follicular contents of facial acne are not only Propionibacterium but also Malassezia spp. J Dermatol. 2016 Aug;43(8):906-11. doi: 10.1111/1346-8138.13245. Epub 2015 Dec 24. PMID: 26705192.
  7. Song YC, Hahn HJ, Kim JY, Ko JH, Lee YW, Choe YB, Ahn KJ. Epidemiologic Study of Malassezia Yeasts in Acne Patients by Analysis of 26S rDNA PCR-RFLP. Ann Dermatol. 2011 Aug;23(3):321-8. doi: 10.5021/ad.2011.23.3.321. Epub 2011 Aug 6. PMID: 21909202; PMCID: PMC3162261.
  8. Tsubuku H, Tsuboi R. Microbiota analysis of pustules in acne vulgaris patients: special focus on Malassezia species. J Tokyo Med Univ. 2020;78(1):48-54.
  9. Niedźwiedzka A, Micallef MP, Biazzo M, Podrini C. The Role of the Skin Microbiome in Acne: Challenges and Future Therapeutic Opportunities. Int J Mol Sci. 2024 Oct 24;25(21):11422. doi: 10.3390/ijms252111422. PMID: 39518974; PMCID: PMC11546345.
  10. Zhang XE, Zheng P, Ye SZ, Ma X, Liu E, Pang YB, He QY, Zhang YX, Li WQ, Zeng JH, Guo J. Microbiome: Role in Inflammatory Skin Diseases. J Inflamm Res. 2024 Feb 15;17:1057-1082. doi: 10.2147/JIR.S441100. PMID: 38375021; PMCID: PMC10876011.
  11. Maître M, Gravier E, Simcic-Mori A, Géniès C, Mias C, Alvarez-Georges S, Noustens A, Bouyer K, Bessou-Touya S, Carballido F, Duplan H. Characterization of the forehead skin microbiome in the early phase of acne. J Eur Acad Dermatol Venereol. 2024 Aug;38 Suppl 7:3-11. doi: 10.1111/jdv.20203. PMID: 39051132.
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