A New Generation of Postbiotics for Skin and Scalp: In Situ Production of Lipid Metabolites by Malassezia

Abstract

Effects of pre- and probiotics on intestinal health are well researched and microbiome-targeting solutions are commercially available. Even though a trend to appreciate the presence of certain microbes on the skin is seeing an increase in momentum, our understanding is limited as to whether the utilization of skin-resident microbes for beneficial effects holds the same potential as the targeted manipulation of the gut microflora. Here, we present a selection of molecular mechanisms of cross-communication between human skin and the skin microbial community and the impact of these interactions on the host's cutaneous health with implications for the development of skin cosmetic and therapeutic solutions. Malassezia yeasts, as the main fungal representatives of the skin microfloral community, interact with the human host skin via lipid mediators, of which several are characterized by exhibiting potent anti-inflammatory activities. This review therefore puts a spotlight on Malassezia and provides a comprehensive overview of the current state of knowledge about these fungal-derived lipid mediators and their capability to reduce aesthetical and sensory burdens, such as redness and itching, commonly associated with inflammatory skin conditions. Finally, several examples of current skin microbiome-based interventions for cosmetic solutions are discussed, and models are presented for the use of skin-resident microbes as endogenous bio-manufacturing platforms for the in situ supplementation of the skin with beneficial metabolites.

Keywords: Malassezia; cosmetics; inflammation; lipid mediator; oxylipin; postbiotics; prebiotics; skin microbiome.

Figure 1

Restoration of skin homeostasis via enzymatic skin microbial conversion of topical omega-3 PUFA into anti-inflammatory/pro-resolving lipid mediators: (A) Skin inflammation and the associated burdens, such as redness and itchiness, can have several triggers, including environmental exposures, as well as a dysbiotic skin microflora. As an example, pathogenic Cutibacterium acnes or Staphylococcus aureus bacterial strains can directly stimulate the skin immune system via the production of immunomodulators, such as, for example, the pro-inflammatory lipid mediator Prostaglandin E2 (PGE₂; depicted in the scheme) [80]. (B) Topical supplementation of skin with excess n-3 PUFA, such as EPA or DHA (DHA structure depicted in the scheme), leads to enzymatic conversion into specialized pro-resolving mediators (SPMs), such as Maresin-1 (MaR1; depicted in the scheme) and/or other anti-inflammatory lipid mediators with postbiotic properties, and reduces products of n-6 PUFA metabolism through direct substrate competition [62]. Enzymatic production of SPMs is mediated by skin-resident fungi (microbial reactions symbolized by blue arrow), such as Malassezia yeasts, thereby resolving inflammation and restoring skin homeostasis. Microbial SPM synthesis can additionally be boosted through support of skin microfloral activity by topical supplementation with pre- or probiotics (see Figure 2).

Figure 2

Targeted manipulation of the skin microbiome to improve skin health. Skin microbiome-derived metabolites with bioactive properties can adversely or beneficially impact skin homeostasis. (A) For example, acneic Cutibacterium acnes strains produce metabolites, such as porphyrins (structure shown), which activate the cutaneous inflammasome [81]. Moreover, acne-affected skin is locally enriched with pro-inflammatory PGE₂ [82]. Topical application of specific probiotics, e.g., non-pathogenic Cutibacterium acnes strains that compete for the same niche, can indirectly reduce the production of pro-inflammatory porphyrins through the displacement of acneic Cutibacterium acnes strains. (B) The skin homeostatic equilibrium can also be supported through the production of beneficial metabolites (symbolized by thicker green arrow), for example by topical supplementation of specific prebiotics, such as Avenanthramide (structure shown) contained in colloidal oats, which supports the growth and microbial activity of mutualistic or commensal microbes, such as Staphylococcus epidermidis bacteria, thus enhancing the microbial production of lactic acid (structure shown) [83] with several attributed favorable effects on skin homeostasis.