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Acne vulgaris is a highly prevalent skin disorder characterized by hyperseborrhea, inflammation, and Propionibacterium acnes overgrowth. Only isotretinoin and hormonal therapy reduce sebum production. To identify a new drug candidate that modulates sebum, we examined the effects of EGCG, the major polyphenol in green tea, on human SEB-1 sebocytes and in patients with acne. In SEB-1 sebocytes, we found that EGCG reduced sebum by modulating the AMPK–SREBP-1 signaling pathway. EGCG also reduces inflammation by suppressing the NF-κB and AP-1 pathways. EGCG also induces cytotoxicity of SEB-1 sebocytes via apoptosis and decreases the viability of P. acnes, thus targeting almost all the pathogenic features of acne. Finally, and most importantly, EGCG significantly improved acne in an 8-week randomized, split-face, clinical trial, and was well tolerated. Our data provide a therapeutic rationale for the use of EGCG in acne.

Background Excessive sebum secretion leads to oily scalps, which can disturb microbial homeostasis and cause various scalp issues, such as sensitive scalp, dandruff, and seborrheic dermatitis. Aims This study aimed to investigate the characteristics of scalp lipids and microbiota in a group of females with excessive sebum secretion using omics technology, and to identify important relationships between feature lipids and dominant functional microbes on oily scalp. Methods Through comparison of three lipidomic sampling methods, we first selected absorbent paper (AP) as a cost‐effective and practical method for untargeted lipidomic profiling. Using this method, we then collected scalp surface lipids from 85 Chinese female emerging adults with varying degrees of excessive sebum and performed internal standard quantified lipidomic profiling using UPLC‐QE Plus‐MS equipped with LipidSearch software version 5.1. Simultaneously, we collected and analyzed scalp microorganisms using PE150 pair‐end metagenomic sequencing on the Illumina NovaSeq platform followed by taxonomic and functional annotation with bioinformatic tools and databases. Afterwards, multivariate statistical analysis and bioinformatics were used to identify feature lipids related to high sebum levels, discern the roles of dominant microbes involved in lipid metabolism, and explore potential correlations between feature lipids and dominant functional microbes of oily scalp. Results After comparison of three lipidomic sampling materials, absorbent paper (AP) was selected to collect scalp surface lipids from 85 volunteers. A total of 13 lipid classes were annotated and the most abundant in ESI (+) mode was triacylglycerol (TG, 99.18%) whereas in ESI (−) mode were fatty acid (FA, 56.94%) and O‐acyl‐(gamma‐hydroxy) FA (OAHFA, 34.15%). We identified 27 TGs and 3 FAs as the major lipid molecules contributing to high sebum levels. Seventy percent of these TGs were unsaturated (33% monounsaturated, 26% diunsaturated, 11% triunsaturated), and 30% were saturated. Meanwhile, we found that although the dominant microorganisms, Cutibacterium, Lawsonella, Malassezia, and Staphylococcus were all involved in lipid metabolism on the scalp, only some of them were related to the degree of sebum level and also displayed species‐specific preferences for lipids. Among them, Lawsonella clevelandensis and Malassezia globosa were weakly negatively associated with both unsaturated and saturated TGs, while Malassezia restricta and Cutibacterium granulosum were only weakly negatively correlated with saturated TGs, and Cutibacterium namnetense was weakly positively correlated with FA (26:0). Conclusions This study describes relevant lipid molecules contributing to higher sebum production, and reveals that L. clevelandensis, M. restricta, M. globosa, C. namnetense, and C. granulosum on the scalp are closely correlated with these lipids, showing species‐specific preference. These findings provide new insights into the interaction between key surface lipids and dominant functional microorganisms on oily scalps.

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. Here we demonstrate that acneic and non acneic strains of Cutibacterium acnes have totally oppositive affinity for lipidic environment. This was correlated with their surface polarity and controls virulence factors expression. This should reflect a differential adaptation to growth on the skin surface or in the sebaceous gland.

Pseudogymnoascus destructans is the causative agent of a fungal infection of bats known as white-nose syndrome (WNS). Since its discovery in 2006, it has been responsible for precipitous declines of several species of cave-dwelling North American bats. While numerous advancements in the understanding of the disease processes underlying WNS have been made in recent years, there are still many aspects of WNS, particularly with respect to pathogen virulence, that remain unknown. In this preliminary investigation, we sought to further elucidate the disease cycle by concentrating on the pathogen, with specific focus on its ability to utilize lipids that compose bat wing sebum and are found in wing membranes, as a substrate for energy and growth. In vitro growth experiments were conducted with the three most common fatty acids that comprise bat sebum: oleic, palmitic, and stearic acids. None of the fatty acids were observed to contribute a significant difference in mean growth from controls grown on SDA, although morphological differences were observed in several instances. Additionally, as an accompaniment to the growth experiments, bat wing explants from Perimyotis subflavus and Eptesicus fuscus were fluorescently stained to visualize the difference in distribution of 16- and 18-carbon chain fatty acids in the wing membrane. Which substrates contribute to the growth of P. destructans is important to understanding the progressive impact P. destructans has on bat health through the course of the disease cycle.

Acne vulgaris is a skin disorder of the sebaceous follicles, involving hyperkeratinization and perifollicular inflammation. Matrix metalloproteinases (MMP) have a predominant role in inflammatory matrix remodeling and hyperproliferative skin disorders. We investigated the expression of MMP and tissue inhibitors of MMP (TIMP) in facial sebum specimens from acne patients, before and after treatment with isotretinoin. Gelatin zymography and Western-blot analysis revealed that sebum contains proMMP-9, which was decreased following per os or topical treatment with isotretinoin and in parallel to the clinical improvement of acne. Sebum also contains MMP-1, MMP-13, TIMP-1, and TIMP-2, as assessed by ELISA and western blot, but only MMP-13 was decreased following treatment with isotretinoin. The origin of MMP and TIMP in sebum is attributed to keratinocytes and sebocytes, since we found that HaCaT keratinocytes in culture secrete proMMP-2, proMMP-9, MMP-1, MMP-13, TIMP-1, and TIMP-2. SZ95 sebocytes in culture secreted proMMP-2 and proMMP-9, which was also confirmed by microarray analysis. Isotretinoin inhibited the arachidonic acid-induced secretion and mRNA expression of proMMP-2 and -9 in both cell types and of MMP-13 in HaCaT keratinocytes. These data indicate that MMP and TIMP of epithelial origin may be involved in acne pathogenesis, and that isotretinoin-induced reduction in MMP-9 and -13 may contribute to the therapeutic effects of the agent in acne.

Today, as 40 years ago, we still rely on a limited number of antibiotics and benzoyl peroxide to treat inflammatory acne. An alternative way of suppressing the growth of Propionibacterium acnes is to target the environment in which it thrives. We conjecture that P. acnes colonises a relatively “extreme” habitat especially in relation to the availability of water and possibly related factors such as ionic strength and osmolarity. We hypothesise that the limiting “nutrient” within pilosebaceous follicles is water since native sebum as secreted by the sebaceous gland contains none. An aqueous component must be available within colonised follicles, and water may be a major factor determining which follicles can sustain microbial populations. One way of preventing microbial growth is to reduce the water activity (aw) of this component with a biocompatible solute of very high water solubility. For the method to work effectively, the solute must be small, easily diffusible, and minimally soluble in sebaceous lipids. Xylose and sucrose, which fulfil these criteria, are nonfermentable by P. acnes and have been used to reduce water activity and hence bacterial colonisation of wounds. A new follicularly targeted topical treatment for acne based on this approach should be well tolerated and highly effective.

Lactobacillus plantarum CJLP55 has anti-pathogenic bacterial and anti-inflammatory activities in vitro. We investigated the dietary effect of CJLP55 supplement in patients with acne vulgaris, a prevalent inflammatory skin condition. Subjects ingested CJLP55 or placebo (n = 14 per group) supplements for 12 weeks in this double-blind, placebo-controlled randomized study. Acne lesion count and grade, skin sebum, hydration, pH and surface lipids were assessed. Metagenomic DNA analysis was performed on urine extracellular vesicles (EV), which indirectly reflect systemic bacterial flora. Compared to the placebo supplement, CJLP55 supplement improved acne lesion count and grade, decreased sebum triglycerides (TG), and increased hydration and ceramide 2, the major ceramide species that maintains the epidermal lipid barrier for hydration. In addition, CJLP55 supplement decreased the prevalence of Proteobacteria and increased Firmicutes, which were correlated with decreased TG, the major skin surface lipid of sebum origin. CJLP55 supplement further decreased the Bacteroidetes:Firmicutes ratio, a relevant marker of bacterial dysbiosis. No differences in skin pH, other skin surface lipids or urine bacterial EV phylum were noted between CJLP55 and placebo supplements. Dietary Lactobacillus plantarum CJLP55 was beneficial to clinical state, skin sebum, and hydration and urine bacterial EV phylum flora in patients with acne vulgaris.

Acne vulgaris is a chronic inflammatory disease — rather than a natural part of the life cycle as colloquially viewed — of the pilosebaceous unit (comprising the hair follicle, hair shaft and sebaceous gland) and is among the most common dermatological conditions worldwide. Some of the key mechanisms involved in the development of acne include disturbed sebaceous gland activity associated with hyperseborrhoea (that is, increased sebum production) and alterations in sebum fatty acid composition, dysregulation of the hormone microenvironment, interaction with neuropeptides, follicular hyperkeratinization, induction of inflammation and dysfunction of the innate and adaptive immunity. Grading of acne involves lesion counting and photographic methods. However, there is a lack of consensus on the exact grading criteria, which hampers the conduction and comparison of randomized controlled clinical trials evaluating treatments. Prevention of acne relies on the successful management of modifiable risk factors, such as underlying systemic diseases and lifestyle factors. Several treatments are available, but guidelines suffer from a lack of data to make evidence-based recommendations. In addition, the complex combination treatment regimens required to target different aspects of acne pathophysiology lead to poor adherence, which undermines treatment success. Acne commonly causes scarring and reduces the quality of life of patients. New treatment options with a shift towards targeting the early processes involved in acne development instead of suppressing the effects of end products will enhance our ability to improve the outcomes for patients with acne. Acne vulgaris is a chronic inflammatory disease of the pilosebaceous gland and is among the most common dermatological conditions worldwide. In this Primer, Feldman and colleagues describe the pathophysiology, diagnostic tools and current treatment options for acne and urge for a better recognition of this disease.

Microorganisms can be equipped with synthetic genetic programs for the production of targeted therapeutic molecules. Cutibacterium acnes is the most abundant commensal of the human skin, making it an attractive chassis to create skin-delivered therapeutics. Here, we report the engineering of this bacterium to produce and secrete the therapeutic molecule neutrophil gelatinase-associated lipocalin, in vivo, for the modulation of cutaneous sebum production. An engineered skin microbe produces a therapeutic molecule that reduces sebum in mice.

The skin microbiome varies across individuals. The causes of these variations are inadequately understood. We tested the hypothesis that inter-individual variation in facial skin microbiome can be significantly explained by variation in sebum and hydration levels in specific facial regions of humans. We measured sebum and hydration from forehead and cheek regions of healthy female volunteers (n = 30). Metagenomic DNA from skin swabs were sequenced for V3-V5 regions of 16S rRNA gene. Altogether, 34 phyla were identified; predominantly Actinobacteria (66.3%), Firmicutes (17.7%), Proteobacteria (13.1%) and Bacteroidetes (1.4%). About 1000 genera were identified; predominantly Propionibacterium (58.6%), Staphylococcus (8.6%), Streptococcus (4.0%), Corynebacterium (3.6%) and Paracoccus (3.3%). A subset (n = 24) of individuals were sampled two months later. Stepwise multiple regression analysis showed that cheek sebum level was the most significant predictor of microbiome composition and diversity followed by forehead hydration level; forehead sebum and cheek hydration levels were not. With increase in cheek sebum, the prevalence of Actinobacteria ( p  =  0.001 )/ Propionibacterium (p  =  0.002 ) increased, whereas microbiome diversity decreased (Shannon Index, p  = 0.032); this was opposite for other phyla/genera. These trends were reversed for forehead hydration levels. Therefore, the nature and diversity of facial skin microbiome is jointly determined by site-specific lipid and water levels in the stratum corneum .