Cécile Clavaud

Acne vulgaris pathogenesis involves complex interactions between sebum hypersecretion, follicular hyperkeratinisation, microbial colonisation and inflammatory cascades. While the bacterial microbiome has been extensively studied, the role of the skin mycobiome, particularly lipophilic Malassezia species, remains less clearly defined in acne‐prone sites. To evaluate evidence for skin mycobiome involvement in acne pathogenesis, a structured narrative review was conducted in PubMed/MEDLINE and PMC, synthesising findings from 14 cross‐sectional studies involving 1650 participants from diverse geographic and ancestry backgrounds. Across sequencing and culture‐based studies, Malassezia was the dominant fungal genus on healthy as well as acne‐prone skin; species‐level data most often identified M. restricta and M. globosa , with occasional reports of M. furfur . Although significant variations were observed in fungal abundance, discrepancies exist between studies due to differences in study design, sampling methods (surface swabs vs. comedone or pustule contents vs. pore strips), culture media (lipid‐supplemented vs. standard), molecular target (ITS1 rDNA vs. other loci) and population demographics. Multiple sequencing studies did not detect significant fungal alpha/beta‐diversity differences between acne and non‐acne skin while confirming Malassezia species dominance. One study highlighted the potential underdiagnosis of Malassezia folliculitis in acne patients, suggesting that misdiagnosis may occur due to overlapping clinical presentations. Future studies should predefine primary outcomes, adjust for multiplicity, report sampling depth (surface vs. follicular), specify fungal rDNA region sequenced, use specific lipid‐supplemented media for Malassezia isolation when culturing, co‐profile bacteria and fungi, and add systematic clinical assessment of Malassezia folliculitis.

Dandruff is a chronic and relapsing scalp condition characterized by flaky scalp. Environmental and host factors (exposome) may alter the sebaceous gland activity, sebum composition, epidermal barrier function, and scalp microbiome balance, resulting in dandruff. Selenium disulfide (SeS2) improves the clinical signs of dandruff. To investigate the mode of action of SeS2 shampoo during treatment and relapse phases. Two single-center studies assessed dandruff severity, subjective efficacy perception, microbial balance, microbiota diversity and sebum lipids. SeS2 significantly (p≤0.01) reduced scaling and led to a significant decrease of Malassezia and Staphylococcus spp. counts in both lesional and non-lesional areas, compared to the vehicle at D28 returning to baseline levels at D56. Cutibacterium spp. levels were not different between the SeS2 and the vehicle treatment groups but had significantly increased with SeS2 (p<0.001) in the lesional zone at D56. The ratio Malassezia spp./Cutibacterium spp. decreased significantly in lesional zones compared to baseline levels, at both D28 and D35 (p<0.001). The total squalene content significantly increased (p<0.05), whereas peroxided squalene had significantly decreased by almost 50% at D31. The ratio triglycerides/free fatty acids significantly (p<0.0001) increased, almost 5-fold, between D0 and D31. SeS2 shampoo was very well tolerated. SeS2 is beneficial in scalp dandruff, even after treatment interruption. It is well tolerated, rebalances the equilibrium between the main bacterial and fungal populations, and improves sebum quality.

The microbiome, as a community of microorganisms and their structural elements, genomes, metabolites/signal molecules, has been shown to play an important role in human health, with significant beneficial applications for gut health. Skin microbiome has emerged as a new field with high potential to develop disruptive solutions to manage skin health and disease. Despite an incomplete toolbox for skin microbiome analyses, much progress has been made towards functional dissection of microbiomes and host-microbiome interactions. A standardized and robust investigation of the skin microbiome is necessary to provide accurate microbial information and set the base for a successful translation of innovations in the dermo-cosmetic field. This review provides an overview of how the landscape of skin microbiome research has evolved from method development (multi-omics/data-based analytical approaches) to the discovery and development of novel microbiome-derived ingredients. Moreover, it provides a summary of the latest findings on interactions between the microbiomes (gut and skin) and skin health/disease. Solutions derived from these two paths are used to develop novel microbiome-based ingredients or solutions acting on skin homeostasis are proposed. The most promising skin and gut-derived microbiome interventional strategies are presented, along with regulatory, safety, industrial, and technical challenges related to a successful translation of these microbiome-based concepts/technologies in the dermo-cosmetic industry.

Objective: Scalp seborrheic dermatitis (SD) is a chronic, relapsing, and inflammatory scalp disease. Studies indicate a global bacterial and fungal microbiota shift of scalp SD, as compared to healthy scalp. Ketoconazole and selenium disulfide (SeS₂) improve clinical signs and symptoms in both scalp dandruff and SD.Aim: The main objective of this study was to investigate the changes in the scalp microbiota diversity and counts in subjects with scalp SD during a two‐phase treatment period.Material and methods: The scalp microbiota and clinical efficacy were investigated in 68 subjects with mild‐to‐moderate scalp SD after an initial one‐month treatment with 2% ketoconazole, and after a 2‐month maintenance phase, either with a 1% SeS₂‐based shampoo or its vehicle.Results: Thirty one subjects in the active and 37 subjects in the vehicle group participated. Ketoconazole provided an improvement of clinical symptoms (adherent (−1.75 p < 0.05), non‐adherent (−1.5, p < 0.05)) flakes and erythema (scores 1.67–0.93, p < 0.001), in an increased fungal diversity and in a significant (p < 0.005) decrease of Malassezia spp. SeS₂ provided an additional clinical improvement (−0.8; p = 0.0002 and −0.7; p = 0.0081 for adherent and non‐adherent flakes, respectively, at Day 84) compared to the vehicle associated with a low Malassezia spp. count and an additional significant (p < 0.001) decrease of the Staphylococcus spp. level.Conclusion: Selenium disulfide provides an additional benefit on the scalp microbiota and in clinical symptoms of SD and dandruff after treatment with ketoconazole. The results confirm the role of Staphylococcus spp. in scalp SD and open possible perspectives for preventing relapses.

Background: Polycyclic aromatic hydrocarbons (PAHs) are of environmental and public health concerns and contribute to adverse skin attributes such as premature skin aging and pigmentary disorder. However, little information is available on the potential roles of chronic urban PAH pollutant exposure on the cutaneous microbiota. Given the roles of the skin microbiota have on healthy and undesirable skin phenotypes and the relationships between PAHs and skin properties, we hypothesize that exposure of PAHs may be associated with changes in the cutaneous microbiota. In this study, the skin microbiota of over two hundred Chinese individuals from two cities in China with varying exposure levels of PAHs were characterized by bacterial and fungal amplicon and shotgun metagenomics sequencing. Results: Skin site and city were strong parameters in changing microbial communities and their assembly processes. Reductions of bacterial-fungal microbial network structural integrity and stability were associated with skin conditions (acne and dandruff). Multivariate analysis revealed associations between abundances of Propionibacterium and Malassezia with host properties and pollutant exposure levels. Shannon diversity increase was correlated to exposure levels of PAHs in a dose-dependent manner. Shotgun metagenomics analysis of samples (n = 32) from individuals of the lowest and highest exposure levels of PAHs further highlighted associations between the PAHs quantified and decrease in abundances of skin commensals and increase in oral bacteria. Functional analysis identified associations between levels of PAHs and abundance of microbial genes of metabolic and other pathways with potential importance in host-microbe interactions as well as degradation of aromatic compounds. Conclusions: The results in this study demonstrated the changes in composition and functional capacities of the cutaneous microbiota associated with chronic exposure levels of PAHs. Findings from this study will aid the development of strategies to harness the microbiota in protecting the skin against pollutants.

The critical CO₂ hydration reaction to bicarbonate and protons is catalyzed by carbonic anhydrases (CAs, EC 4.2.1.1). Their physiological role is to assist the transport of the CO₂ and HCO₃⁻ at the cellular level, which will not be ensured by the low velocity of the uncatalyzed reaction. CA inhibition may impair the growth of microorganisms. In the yeasts, Candida albicans and Malassezia globosa, the activity of the unique β-CA identified in their genomes was demonstrated to be essential for growth of the pathogen. Here, we decided to investigate the sulfonamide inhibition profile of the homologous β-CA (MreCA) identified in the genome of Malassezia restricta, an opportunistic pathogen triggering dandruff and seborrheic dermatitis. Among 40 investigated derivatives, the best MreCA sulfonamide inhibitors were dorzolamide, brinzolamide, indisulam, valdecoxib, sulthiam, and acetazolamide (K_I < 1.0 μM). The MreCA inhibition profile was different from those of the homologous enzyme from Malassezia globosa (MgCA) and the human isoenzymes (hCA I and hCA II). These results might be useful to for designing CA inhibitor scaffolds that may selectively inhibit the dandruff-producing fungi.

Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes, which catalyze the crucial physiological CO₂ hydration/dehydration reaction (CO₂ + H₂O ⇌ HCO₃⁻ + H⁺) balancing the equilibrium between CO₂, H₂CO₃, HCO₃⁻ and CO₃²⁻. It has been demonstrated that their selective inhibition alters the equilibrium of the metabolites above affecting the biosynthesis and energy metabolism of the organism. In this context, our interest has been focalized on the fungus Malassezia restricta, which may trigger dandruff and seborrheic dermatitis altering the complex bacterial and fungal equilibrium of the human scalp. We investigated a rather large number of inorganic metal-complexing anions (a well-known class of CA inhibitors) for their interaction with the β-CA (MreCA) encoded by the M. restricta genome. The results were compared with those obtained for the two human α-CA isoforms (hCAI and hCAII) and the β-CA from Malassezia globosa. The most effective MreCA inhibitors were diethyldithiocarbamate, sulfamide, phenyl arsenic acid, stannate, tellurate, tetraborate, selenocyanate, trithiocarbonate, and bicarbonate. The different K_I values obtained for the four proteins investigated might be attributed to the architectural features of their catalytic site. The anion inhibition profile is essential for better understanding the inhibition/catalytic mechanisms of these enzymes and for designing novel types of inhibitors, which may have clinical applications for the management of dandruff and seborrheic dermatitis.

The cloning, purification, and initial characterization of the β-carbonic anhydrase (CA, EC 4.2.1.1) from the genome of the opportunistic pathogen Malassezia restricta (MreCA), which a fungus involved in dandruff and seborrheic dermatitis (SD), is reported. MreCA is a protein consisting of 230 amino acid residues and shows high catalytic activity for the hydration of CO₂ into bicarbonate and protons, with the following kinetic parameters: k_cat of 1.06 × 10⁶ s⁻¹ and k_cat/K_M of 1.07 × 10⁸ M⁻¹ s⁻¹. It is also sensitive to inhibition by the sulfonamide acetazolamide (K_I of 50.7 nM). Phylogenetically, MreCA and other CAs from various Malassezia species seem to be on a different branch, distinct from that of other β-CAs found in fungi, such as Candida spp., Saccharomyces cerevisiae, Aspergillus fumigatus, and Sordaria macrospora, with only Cryptococcus neoformans and Ustilago maydis enzymes clustering near MreCA. The further characterization of this enzyme and the identification of inhibitors that may interfere with its life cycle might constitute new strategies for fighting dandruff and SD.

Malassezia restricta , one of the predominant basidiomycetous yeasts present on human skin, is involved in scalp disorders. Here, we report the complete genome sequence of the lipophilic Malassezia restricta CBS 7877 strain, which will facilitate the study of the mechanisms underlying its commensal and pathogenic roles within the skin microbiome.