Acne and fungus: an unexpected relationship

Acne: beyond the skin's surface

Before diving into the heart of the relationship between acne and fungi, it is essential to fully understand what acne is, its multifactorial causes, and its impact on quality of life. Acne vulgaris is not simply a "teenage problem" or the result of poor hygiene. It is a chronic inflammatory condition of the pilosebaceous unit, influenced by a complex interaction of genetic, hormonal, bacterial, and environmental factors.

Inflammation, once considered a consequence of acne, is now recognized as a primary pathogenic element, beginning even before the formation of comedones. Exploring this complexity is the first step to appreciating how an organism like a fungus can play a significant role.

The classic pathophysiology of acne: the four pillars

The traditional model of acne rests on four main mechanisms that, interacting with each other, lead to the formation of lesions.

Hyperkeratinization of the hair follicle

The process begins with an abnormal desquamation of the corneocytes lining the follicle duct. Normally, these cells detach and are expelled to the surface along with sebum. In acne, this desquamation process becomes dysregulated, leading to the adhesion of corneocytes and the formation of a keratinous "plug" that obstructs the duct. This represents the primum movens of the acne lesion, the microcomedone, invisible to the naked eye but already the site of alterations.

Hyperseborrhea: the excessive production of sebum

The sebaceous glands, under the stimulation of androgen hormones (such as testosterone and dihydrotestosterone or DHT), produce an excessive amount of sebum. This sebum, rich in triglycerides, provides an abundant lipid substrate which, together with the follicle obstruction, creates an anaerobic, nutrient-rich environment, perfect for the proliferation of microorganisms. It is precisely in this context that the role of the microbiome, including the fungal one, becomes crucial.

Bacterial colonization by Cutibacterium acnes

For years, the bacterium Cutibacterium acnes (formerly known as Propionibacterium acnes) was considered the main antagonist in acne. This gram-positive, commensal skin bacterium proliferates in the anaerobic environment of the obstructed follicle. Here, bacterial lipases break down sebum triglycerides into free fatty acids, which irritate the follicular wall and trigger an inflammatory response. Furthermore, some strains of C. acnes are able to activate the innate immune system through various mechanisms, worsening inflammation.

Inflammation and immune response

Inflammation is a common thread in all stages of acne. It can be triggered by irritation from free fatty acids, components of the bacterial wall of C. acnes, and, as we will see, by elements of the mycobiota. Immune cells release pro-inflammatory cytokines (such as IL-1α, TNF-α), which recruit other inflammatory cells, leading to the redness, swelling, and pain characteristic of inflamed papules and pustules.

The skin microbiome: a complex ecosystem

Our skin is not a sterile surface, but a dynamic and diverse ecosystem hosting trillions of bacteria, viruses, archaea, and fungi. This collection of microorganisms, the skin microbiome, lives in a delicate balance of mutualism with the host. The concept of "dysbiosis", i.e., the alteration of this balance, is central to understanding many skin pathologies, including acne. It is no longer about the presence or absence of a single pathogen, but an imbalance in the entire microbial community.

The mycobiota: the fungal component of the skin

While the skin bacteriome has been widely studied, the fungal component, the mycobiota, has received less attention until recent times. The dominant fungus on healthy human skin is the genus Malassezia. Other species present in smaller amounts include Candida, Cryptococcus, and Rhodotorula. The mycobiota varies in diversity and abundance depending on the skin site, age, sex, and environmental factors.

Malassezia: an opportunistic commensal

Yeasts of the genus Malassezia are lipophilic, meaning they depend on lipids for their survival. This explains their abundance in the sebaceous areas of the body, such as the face, scalp, and chest. Under normal conditions, Malassezia lives in peace with its host. However, in predisposed individuals and under particular conditions, it can become opportunistic and contribute to pathologies like seborrheic dermatitis and pityriasis versicolor. Its potential role in acne is a rapidly evolving field of research.

The turning point: the role of Malassezia in acne

The classic pathogenic triad (hyperkeratinization, hyperseborrhea, C. acnes) is giving way to a more inclusive model. Growing evidence suggests that Malassezia is not a mere spectator in acne, but an involved actor, especially in certain specific forms.

Scientific evidence of the link

Several studies have compared the mycobiota of acne patients and healthy controls. A 2021 meta-analysis published in the "Journal of Dermatological Science" found that the relative abundance of Malassezia, particularly species M. globosa and M. restricta, was significantly higher in the lesional skin of acne patients compared to their healthy skin or the skin of controls. This indicates a fungal dysbiosis associated with the disease.

Proposed mechanisms for Malassezia's action

How can a yeast like Malassezia contribute to acne? The proposed mechanisms are multiple and mirror, in a way, those of C. acnes.

1. Hydrolysis of triglycerides and release of irritating free fatty acids

Just like C. acnes, Malassezia possesses lipase enzymes. These enzymes break down sebum triglycerides into free fatty acids. In addition to direct irritation of the follicular wall, this process provides Malassezia with the saturated fatty acids it needs to grow, creating a vicious cycle. The released unsaturated fatty acids, on the other hand, can inhibit the growth of other microorganisms, further altering the microbiome balance.

2. Activation of the innate immune system

The cell wall of Malassezia contains polysaccharides and glycoproteins that can be recognized by pattern recognition receptors (PRRs) on skin immune cells, such as keratinocytes. This recognition triggers a cascade of signals leading to the release of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), fueling the inflammation that is central to the pathogenesis of papulo-pustular and nodulo-cystic acne.

3. Biofilm formation

Some studies suggest that Malassezia can form biofilms. Biofilms are structured communities of microorganisms enclosed in an extracellular polymeric matrix that protects them from antibiotics and host defenses. The presence of a fungal biofilm within the follicle could make the acne process more persistent and resistant to conventional treatments.

Fungal acne or "Fungal Acne": a specific subtype

The term "fungal acne" has become popular online, although it is not an official dermatological diagnosis. In technical terms, it is often referred to as pityrosporum folliculitis, an inflammation of the hair follicles caused mainly by an overgrowth of Malassezia. It presents clinically with small, monomorphic papules and pustules, often itchy, typically located on the chest, back, and sometimes the face. It is crucial to distinguish it from classic acne vulgaris, as the treatment is different: instead of classic antibiotics or retinoids, topical or systemic antifungals are used.

Table 1: comparison between acne vulgaris and Malassezia folliculitis (fungal acne)

Mycotherapy for acne: the power of medicinal mushrooms

If some fungi can contribute to acne, others, medicinal mushrooms, can offer promising therapeutic solutions. Mycotherapy, the use of mushrooms for medicinal purposes, boasts a millennia-old history in Traditional Chinese Medicine and is gaining a solid scientific foundation. Medicinal mushrooms are extremely rich in beta-glucans, triterpenes, enzymes, and antioxidants, molecules with potent immune-modulating, anti-inflammatory, and prebiotic properties.

Reishi (Ganoderma Lucidum): the skin adaptogen

Reishi, known as the "mushroom of immortality," is one of the most studied and powerful medicinal mushrooms. Its benefits for acne-affected skin are multifactorial.

Anti-inflammatory and immunomodulatory properties

Reishi's triterpenes and beta-glucans are able to modulate the immune response, suppressing the excessive production of pro-inflammatory cytokines like TNF-α. In an in vitro study on human keratinocyte cultures, Reishi extract significantly inhibited the release of IL-8 induced by C. acnes. This means that Reishi can act at the root of the acne inflammatory process, calming the "cytokine storm" that causes redness and swelling.

5-Alpha reductase inhibitory activity

The enzyme 5-alpha reductase converts testosterone into the more potent DHT, which strongly stimulates the sebaceous glands. Preliminary studies suggest that Reishi's triterpenes may inhibit this enzyme, thus acting on the hormonal cause of hyperseborrhea. Although more human research is needed, this mechanism of action is extremely promising.

Chaga (Inonotus Obliquus): the forest antioxidant

Chaga, a parasite of birch trees, has one of the highest ORAC (Oxygen Radical Absorbance Capacity) values in the plant kingdom, higher than blueberries and pomegranates.

Protection from oxidative stress

Acne-prone skin is subject to high oxidative stress. Chronic inflammation generates free radicals that further damage tissues, perpetuating the acne cycle and contributing to post-inflammatory hyperpigmentation (dark spots). Chaga's powerful antioxidants, such as polysaccharides and melanin, help neutralize these free radicals, protecting the skin from oxidative damage and supporting healing processes.

Shiitake (Lentinula Edodes): the detoxifier and prebiotic

Shiitake, besides being a delicious edible mushroom, possesses remarkable medicinal properties, thanks mainly to its active polysaccharide, lentinan.

Liver support and detoxification

A healthy liver is crucial for balanced hormone metabolism and the elimination of toxins. Shiitake supports liver function, helping the body process and eliminate excess hormones that can contribute to acne.

Prebiotic effect on the gut and skin microbiome

Lentinan and other beta-glucans in Shiitake act as prebiotics, feeding the beneficial bacteria in our gut. There is a strong gut-skin axis: a healthy gut microbiome is associated with reduced systemic inflammation and improvement in conditions like acne. A healthy gut can translate to healthier skin.

Table 2: properties of medicinal mushrooms relevant for acne care

Statistics, prevalence, and psychosocial impact of acne

Understanding the extent of the acne problem is fundamental to appreciating the importance of innovative therapeutic approaches. Acne affects a huge portion of the global population, with an impact that goes far beyond the skin's surface.

Global and national epidemiological data

Acne is the eighth most prevalent disease worldwide. It affects about 9.4% of the global population, with prevalence peaks during adolescence. In Italy, it is estimated that acne affects 80-90% of adolescents, with a significant percentage (about 20-30%) continuing to suffer from it in adulthood, particularly women (adult female acne). Up to 15% of cases can be moderate or severe, requiring specialist treatments.

The psychosocial burden: quality of life and mental health

Acne is not a fatal disease, but its impact on quality of life is comparable to that of chronic conditions like asthma, diabetes, or epilepsy. Studies have shown that patients with acne have higher rates of:

• Anxiety and depression
• Social phobia and isolation
• Low self-esteem and body dissatisfaction
• Difficulties in interpersonal and professional relationships

Effectively addressing acne, therefore, means taking care of not only the skin but also the person's psychological well-being.

Acne: towards an integrated management of the pathology

The landscape of understanding and treating acne is rapidly evolving. The role of the mycobiota, particularly Malassezia, adds an important piece to the pathogenic puzzle, explaining why some cases do not respond to traditional antibacterial therapies and paving the way for targeted antifungal treatments. At the same time, the vast arsenal of bioactive compounds found in medicinal mushrooms offers a promising, natural, and multifactorial way to counteract acne by acting simultaneously on inflammation, hormonal imbalance, oxidative stress, and microbiome dysbiosis.

The future of acne management lies increasingly in an integrated and personalized approach, considering the individual in their entirety: their skin, their microbiome, their immune system, their hormones, and their lifestyle. In this context, mycology, both in the study of pathogens and remedies, is destined to play an increasingly central role.