The microorganisms inhabiting human skin must overcome numerous challenges that typically impede microbial growth, including low pH, osmotic pressure, and low nutrient availability. Yet the skin microbiota thrive on the skin and have adapted to these stressful conditions. The limited nutrients available for microbial use in this unique niche include those from host-derived sweat, sebum, and corneocytes. Here, we have developed physiologically relevant, synthetic skin-like growth media composed of compounds present in sweat and sebum. We find that skin-associated bacterial species exhibit unique growth profiles at different concentrations of artificial sweat and sebum. Most strains evaluated demonstrate a preference for high sweat concentrations, while the sebum preference is highly variable, suggesting that the capacity for sebum utilization may be a driver of the skin microbial community structure. In particular, the prominent skin commensal Staphylococcus epidermidis exhibits the strongest preference for sweat while growing equally well across sebum concentrations. Conversely, the growth of Corynebacterium kefirresidentii, another dominant skin microbiome member, is dependent on increasing concentrations of both sweat and sebum but only when sebum is available, suggesting a lipid requirement of this species. Furthermore, we observe that strains with similar growth profiles in the artificial media cluster by phylum, suggesting that phylogeny is a key factor in sweat and sebum use. Importantly, these findings provide an experimental rationale for why different skin microenvironments harbor distinct microbiome communities. In all, our study further emphasizes the importance of studying microorganisms in an ecologically relevant context, which is critical for our understanding of their physiology, ecology, and function on the skin. IMPORTANCE The human skin microbiome is adapted to survive and thrive in the harsh environment of the skin, which is low in nutrient availability. To study skin microorganisms in a system that mimics the natural skin environment, we developed and tested a physiologically relevant, synthetic skin-like growth medium that is composed of compounds found in the human skin secretions sweat and sebum. We find that most skin-associated bacterial species tested prefer high concentrations of artificial sweat but that artificial sebum concentration preference varies from species to species, suggesting that sebum utilization may be an important contributor to skin microbiome composition. This study demonstrates the utility of a skin-like growth medium, which can be applied to diverse microbiological systems, and underscores the importance of studying microorganisms in an ecologically relevant context.

Lipidomics is strategic in the discovery of biomarkers of neurodegenerative diseases (NDDs). The skin surface lipidome bears the potential to provide biomarker candidates in the detection of pathological processes occurring in distal organs. We investigated the sebum composition to search diagnostic and, possibly, prognostic, biomarkers of Alzheimer's disease (AD) and Parkinson's disease (PD). The observational study included 64 subjects: 20 characterized as "probable AD with documented decline", 20 as "clinically established PD", and 24 healthy subjects (HS) of comparable age. The analysis of sebum by GCMS and TLC retrieved the amounts (µg) of 41 free fatty acids (FFAs), 7 fatty alcohols (FOHs), vitamin E, cholesterol, squalene, and total triglycerides (TGs) and wax esters (WEs). Distributions of sebum lipids in NDDs and healthy conditions were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). The deranged sebum composition associated with the PD group showed incretion of most composing lipids compared to HS, whereas only two lipid species (vitamin E and FOH14:0) were discriminant of AD samples and presented lower levels than HS sebum. Thus, sebum lipid biosynthetic pathways are differently affected in PD and AD. The characteristic sebum bio-signatures detected support the value of sebum lipidomics in the biomarkers search in NDDs.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD.

At Canadian Blood Services, despite the use of 2% chlorhexidine and 70% isopropyl alcohol (standard disinfectant, SD) prior to venipuncture, Cutibacterium acnes evades eradication and is a major contaminant of platelet concentrates (PCs). Since C. acnes forms bacterial aggregates known as biofilms in the sebaceous niches of the skin, this study aimed to assess whether sebum-like components impact disinfectant efficacy against C. acnes leading to its dominance as a PC contaminant. C. acnes mono-species and dual-species biofilms (C. acness and a transfusion-relevant Staphylococcus aureus isolate) were formed in the presence and absence of sebum-like components and exposed to SD, a hypochlorous acid-based disinfectant (Clinisept+, CP), or a combination of both disinfectants to assess disinfectant efficacy. Our data indicate that sebum-like components significantly reduce the disinfectant efficacy of all disinfectant strategies tested against C. acnes in both biofilm models. Furthermore, though none of the disinfectants led to bacterial eradication, the susceptibility of C. acnes to disinfectants was heightened in an isolate-dependent manner when grown in the presence of S. aureus. The reduction of skin disinfection efficacy in the presence of sebum may contribute to the overrepresentation of C. acnes as a PC contaminant and highlights the need for improved disinfection strategies.

The majority of metabolomics studies to date have utilised blood serum or plasma, biofluids that do not necessarily address the full range of patient pathologies. Here, correlations between serum metabolites, salivary metabolites and sebum lipids are studied for the first time. 83 COVID-19 positive and negative hospitalised participants provided blood serum alongside saliva and sebum samples for analysis by liquid chromatography mass spectrometry. Widespread alterations to serum-sebum lipid relationships were observed in COVID-19 positive participants versus negative controls. There was also a marked correlation between sebum lipids and the immunostimulatory hormone dehydroepiandrosterone sulphate in the COVID-19 positive cohort. The biofluids analysed herein were also compared in terms of their ability to differentiate COVID-19 positive participants from controls; serum performed best by multivariate analysis (sensitivity and specificity of 0.97), with the dominant changes in triglyceride and bile acid levels, concordant with other studies identifying dyslipidemia as a hallmark of COVID-19 infection. Sebum performed well (sensitivity 0.92; specificity 0.84), with saliva performing worst (sensitivity 0.78; specificity 0.83). These findings show that alterations to skin lipid profiles coincide with dyslipidaemia in serum. The work also signposts the potential for integrated biofluid analyses to provide insight into the whole-body atlas of pathophysiological conditions.

The skin microbiome and sebum may be associated with inflammation-related diseases of the scalp. To assess the pathogenesis and progression of androgenetic alopecia (AGA), we analyzed the composition of sebum and the bacterial and fungal microbiomes of the scalps of 118 Japanese male individuals with and without AGA, then discussed their roles in the pathogenesis of AGA. Sebum triglyceride and palmitic acid contents were higher in the AGA group than in the non-AGA group. Malassezia restricta, a lipophilic fungus that consumes palmitic acid, was abundant on the scalps of patients with AGA. Cutibacterium, Corynebacterium, and Staphylococcus were the most common genera in both groups, and patients with AGA exhibited scalp dysbiosis (increased abundance of Cutibacterium and decreased abundance of Corynebacterium). Our findings suggest that both sebum and the bacterial and fungal microbiomes of the scalp may be involved in the development of AGA.

Parkinson's disease (PD) is a progressive neurodegenerative disease presenting with motor and non-motor symptoms, including skin disorders (seborrheic dermatitis, bullous pemphigoid, and rosacea), skin pathological changes (decreased nerve endings and alpha-synuclein deposition), and metabolic changes of sebum. Recently, a transcriptome method using RNA in skin surface lipids (SSL-RNAs) which can be obtained non-invasively with an oil-blotting film was reported as a novel analytic method of sebum. Here we report transcriptome analyses using SSL-RNAs and the potential of these expression profiles with machine learning as diagnostic biomarkers for PD in double cohorts (PD [n = 15, 50], controls [n = 15, 50]). Differential expression analysis between the patients with PD and healthy controls identified more than 100 differentially expressed genes in the two cohorts. In each cohort, several genes related to oxidative phosphorylation were upregulated, and gene ontology analysis using differentially expressed genes revealed functional processes associated with PD. Furthermore, machine learning using the expression information obtained from the SSL-RNAs was able to efficiently discriminate patients with PD from healthy controls, with an area under the receiver operating characteristic curve of 0.806. This non-invasive gene expression profile of SSL-RNAs may contribute to early PD diagnosis based on the neurodegeneration background.

Cutibacterium acnes, former Proprionibacterium acnes, is a heterogeneous species including acneic bacteria such as the RT4 strain, and commensal bacteria such as the RT6 strain. These strains have been characterized by metagenomic analysis but their physiology was not investigated until now. Bacteria were grown in different media, brain heart infusion medium (BHI), reinforced clostridial medium (RCM), and in sebum like medium (SLM) specifically designed to reproduce the lipid rich environment of the sebaceous gland. Whereas the RT4 acneic strain showed maximal growth in SLM and lower growth in RCM and BHI, the RT6 non acneic strain was growing preferentially in RCM and marginally in SLM. These differences were correlated with the lipophilic surface of the RT4 strain and to the more polar surface of the RT6 strain. Both strains also showed marked differences in biofilm formation activity which was maximal for the RT4 strain in BHI and for the RT6 strain in SLM. However, cytotoxicity of both strains on HaCaT keratinocytes remained identical and limited. The RT4 acneic strain showed higher inflammatory potential than the RT6 non acneic strain, but the growth medium was without significant influence. Both bacteria were also capable to stimulate β-defensine 2 secretion by keratinocytes but no influence of the bacterial growth conditions was observed. Comparative proteomics analysis was performed by nano LC-MS/MS and revealed that whereas the RT4 strain only expressed triacylglycerol lipase, the principal C. acnes virulence factor, when it was grown in SLM, the RT6 strain expressed another virulence factor, the CAMP factor, exclusively when it was grown in BHI and RCM. This study demonstrates the key influence of growth conditions on virulence expression by C. acnesand suggest that acneic and non acneic strains are related to different environmental niches.

Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand.

Microbial dysbiosis in the skin has been implicated in the pathogenesis of atopic dermatitis (AD); however, whether and how changes in the skin microbiome initiate skin inflammation, or vice versa, remains poorly understood. Here, we report that the levels of sebum and its microbial metabolite, propionate, were lower on the skin surface of AD patients compared with those of healthy individuals. Topical propionate application attenuated skin inflammation in mice with MC903-induced AD-like dermatitis by inhibiting IL-33 production in keratinocytes, an effect that was mediated through inhibition of HDAC and regulation of the AhR signaling pathway. Mice lacking sebum spontaneously developed AD-like dermatitis, which was improved by topical propionate application. A proof-of-concept clinical study further demonstrated the beneficial therapeutic effects of topical propionate application in AD patients. In summary, we have uncovered that the dysregulated sebum-microbial metabolite-IL-33 axis might play an initiating role in AD-related skin inflammation, thereby highlighting novel therapeutic strategies for the treatment of AD.

Genomes are dynamic biological units, with processes of gene duplication and loss triggering evolutionary novelty. The mammalian skin provides a remarkable case study on the occurrence of adaptive morphological innovations. Skin sebaceous glands (SGs), for instance, emerged in the ancestor of mammals serving pivotal roles, such as lubrication, waterproofing, immunity, and thermoregulation, through the secretion of sebum, a complex mixture of various neutral lipids such as triacylglycerol, free fatty acids, wax esters, cholesterol, and squalene. Remarkably, SGs are absent in a few mammalian lineages, including the iconic Cetacea. We investigated the evolution of the key molecular components responsible for skin sebum production: Dgat2l6, Awat1, Awat2, Elovl3, Mogat3, and Fabp9. We show that all analyzed genes have been rendered nonfunctional in Cetacea species (toothed and baleen whales). Transcriptomic analysis, including a novel skin transcriptome from blue whale, supports gene inactivation. The conserved mutational pattern found in most analyzed genes, indicates that pseudogenization events took place prior to the diversification of modern Cetacea lineages. Genome and skin transcriptome analysis of the common hippopotamus highlighted the convergent loss of a subset of sebum-producing genes, notably Awat1 and Mogat3. Partial loss profiles were also detected in non-Cetacea aquatic mammals, such as the Florida manatee, and in terrestrial mammals displaying specialized skin phenotypes such as the African elephant, white rhinoceros and pig. Our findings reveal a unique landscape of "gene vestiges" in the Cetacea sebum-producing compartment, with limited gene loss observed in other mammalian lineages: suggestive of specific adaptations or specializations of skin lipids.

Sebocytes are the major cells of sebaceous gland. The essential role of sebocytes is the production of sebum, a specific lipid mixture, that covers the body surface and provides the barrier function. At puberty, sebum production increases under the effects of various stimuli including androgens and insulin-like growth factor-1 (IGF-1). Excessive sebum production changes the microenvironment surrounding hair follicle, often leading to the onset of acne.

The COVID-19 pandemic has led to an unprecedented demand for testing - for diagnosis and prognosis - as well as for investigation into the impact of the disease on the host metabolism. Sebum sampling has the potential to support both needs by looking at what the virus does to us, rather than looking for the virus itself.

Lipidomics is advantageous in the study of sebum perturbations occurring in acne. An extended evaluation of the sebum lipid profiles in acne-prone sebaceous areas is lacking in dark skin. Yet, there is a void space in understanding how the building blocks of sebum lipids, i.e. individual fatty acids (FAs), are intertwined with acne-prone skin. We aimed to determine the sebum lipidome in facial areas of adolescents with and without acne in Nigeria. A cross-sectional analytical study was conducted in 60 adolescents/young adults divided in 30 acne patients (15F, 15M) and 30 age and sex-matched controls. Sebum samples obtained from foreheads and cheeks were analysed separately by gas chromatography-mass spectrometry (GCMS) and thin layer chromatography (HPTLC). Distributions of sebum components were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). Sebum incretion in acne was paralleled by significantly higher abundance of triglycerides, wax esters, and squalene together with monounsaturated FAs (MUFAs), and straight chain saturated FAs (SFAs), especially those with odd-carbon chain, i.e. C13:0, C15:0, and C17:0. Profiling weight/weight percentage of individual components revealed that, in acne, the free FAs (FFAs) array was shifted towards higher relative abundance of the SFAs C15:0, C16:0, and C17:0 and lower percentage of the anteiso-branched FFAs with 12, 14, 16, and 18 carbons. In acne patients, MUFAs and PUFAs were quantitatively increased and decreased on foreheads and cheeks, respectively. Relative abundance of fatty alcohols was decreased in acne independent on the site. The results indicated that acne associates with site-specific derangement of the pathways regulating the balance among odd straight-chain and branched-chain SFAs, MUFAs, which included sapienate (C16:1n-10), PUFAs, and squalene.

Sebum content, skin hydration and acidic skin pH are major factors in maintaining skin health. Various nutrients are reported to influence skin health, but the effect of dietary patterns (DPs) on skin health is unclear. In this study, we considered the DPs associated with these three skin health parameters in 84 healthy adults aged 19⁻37 years. Dietary intake was assessed using a food frequency questionnaire (FFQ) and skin health parameters were determined on the forehead of each subject. Among the four DPs extracted from the FFQ, DP2, characterized by a high intake of cereals, potatoes and starch, saccharides and fish and shellfish, was negatively associated with skin hydration. DP3, characterized by a high intake of potatoes and starch, seeds and nuts, fruits and eggs, was positively associated with acidic skin pH only before adjusting for potential confounders. On the other hand, DP4, characterized by a low intake of beans, and a high intake of meats, dairy products and beverages and alcohol, was negatively associated with acidic skin pH and positively associated with sebum content. The data stratified by sex revealed a negative association between skin hydration and DP2 in males and a negative association between sebum content and DP3 and a positive association between sebum content and DP4 in females. In conclusion, we demonstrated that specific DPs were associated with sebum content, skin hydration and pH in healthy Korean adults and that those associations were affected by sex.

Terminalia chebula (TC) is a medicinal plant that exhibits antioxidant, anti-inflammatory, and antibacterial properties and that is widely used in Ayurveda and herbal formulations. However, the skin effects of TC as an oral supplement have not been studied. The objective of this study is to determine if oral TC fruit extract supplementation can modulate the skin's sebum production and reduce the appearance of wrinkles. A prospective double-blind placebo-controlled study was conducted on healthy females aged 25-65. Subjects were supplemented with an oral placebo or Terminalia chebula (250 mg capsule, Synastol TC) capsules twice daily for eight weeks. A facial image collection and analysis system was used to assess the facial appearance of wrinkle severity. Standardized, non-invasive tools were used to measure facial moisture, sebum production, transepidermal water loss, melanin index and erythema index. For those who had a baseline sebum excretion rate >80 ug/cm2, TC supplementation produced a significant decrease in forehead sebum excretion rate compared to the placebo at four weeks (-17 decrease vs. 20% increase, p = 0.07) and at eight weeks (-33% decrease vs. 29% increase, p < 0.01). Cheek erythema decreased by 2.2% at eight weeks, while the placebo treatment increased cheek erythema by 1.5% (p < 0.05). Facial wrinkles decreased by 4.3% in the TC group and increased by 3.9% in the placebo group after eight weeks of supplementation (p < 0.05). TC supplementation reduces facial sebum and improves the appearance of wrinkles. Future studies should consider evaluating oral TC as adjuvant therapy for acne vulgaris.

Alcoholamines are widely used as auxiliary substances in various topical preparations. Their impact on the components of skin sebum allows them to be used in preparations that cleanse the skin of sebum in hair follicles. We measured the effects of various concentrations of aqueous solutions of AMPD (2-amino-2-methyl-1,3-propanediol) on model skin sebum. The volume of reacted sebum was calculated using two methods: optical assessment of the interaction of alcoholamines with the components of model skin sebum and determination of the reacted volume of model skin sebum based on the measurements of changes in the pH of the AMPD solutions. Both methods showed that the most favorable AMPD concentration for model sebum penetration was approximately 1-2%. Lower values of alcoholamine caused premature exhaustion from the solution. Excessively high concentrations resulted in the formation of a dense layer of products hindering effective skin cleansing.

The increased interest in natural cosmetics has resulted in a higher market demand for preservative-free products based on herbal ingredients. An innovative W/O/W type emulsions containing herbal extracts were prepared directly; its cation form was induced by an ethanolic rosemary extract and stabilized using weak herbal gels. Due to the wide phytochemical composition of herbal extracts and the presence of alcohol in the emulsion system, which can cause skin irritation, sensitization or dryness when applied topically, the safety of the investigated drug delivery system is necessary. The aim of our study was to estimate the potential of W/O/W emulsions based on natural ingredients for skin irritation and phototoxicity using reconstructed 3D epidermis models in vitro and to evaluate in vivo its effect on human skin moisture, sebum content and pigmentation by biomedical examination using a dermatoscopic camera and corneometer. According to the results obtained after in vitro cell viability test the investigated emulsion was neither irritant nor phototoxic to human skin keratinocytes. W/O/W emulsion did not cause skin dryness in vivo, despite the fact that it contained ethanol. We can conclude that the emulsion is safe for use as a leave-on product due to the positive effect on human skin characteristics or as a semisolid pharmaceutical base where active compounds could be encapsulated.

In adipocytes and sebocytes, lipid droplet proteins control the storage of lipids in organized droplets and their release on demand. The contribution of lipid droplet proteins to the pathogenesis of acne is plausible because they control the levels of comedogenic free fatty acids. The expression of two lipid droplet proteins, CIDEA and PLIN2, was analyzed in the skin of patients with acne by immunohistochemistry and western blotting. The design of clinical protocols allowed correlating the expression of CIDEA and PLIN2 with both comedogenesis and the release of free fatty acids. Both proteins were detected by immunohistochemistry in the sebaceous glands of patients with acne, with a disturbed expression pattern of PLIN2 compared with that in the controls. Higher levels of PLIN2 and CIDEA, as detected by western blotting in the infundibulum, significantly correlated with lower ongoing comedogenesis over 48 weeks of Silybum marianum fruit extract application. Accordingly, free fatty acid release from sebum triglycerides was significantly decreased, as shown with two distinct methods. The data are consistent with the expected role of PLIN2 and CIDEA in the prevention of comedogenic free fatty acid release. Modulation of PLIN2 and CIDEA expression appears as a sound target for the maintenance of low comedogenic sebum and acne-prone skin health.

Objective. Bokusoku (BK) is an extract from the Quercus cortex used in folk medicine for treatment of skin disorders and convergence, and is present in jumihaidokuto, a traditional Japanese medicine that is prescribed for purulent skin diseases like acne vulgaris. The excess of sebum production induced by androgen is involved in the development of acne. Our aim is to examine whether BK and its constituents inhibit testosterone metabolism and testosterone-induced sebum synthesis. Methods. Measurements of 5α-reductase activity and lipogenesis were performed using rat liver microsomes and hamster sebocytes, respectively. Results. BK dose-dependently reduced the conversion of testosterone to a more active androgen, dihydrotestosterone in a 5α-reductase enzymatic reaction. Twenty polyphenols in BK categorized as gallotannin, ellagitannin, and flavonoid were identified by LC-MS/MS. Nine polyphenols with gallate group, tetragalloyl glucose, pentagalloyl glucose, eugeniin, 1-desgalloyl eugeniin, casuarinin, castalagin, stenophyllanin C, (-)-epicatechin gallate, and (-)-epigallocatechin gallate, inhibited testosterone metabolism. In particular, pentagalloyl glucose showed the strongest activity. BK and pentagalloyl glucose suppressed testosterone-induced lipogenesis, whereas they weakly inhibited the lipogenic action of insulin. Conclusions. BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne.