The Mechanism and Research Progress of Skin Microbiota in Pathogenesis of Acne

Propionibacterium acnes and Sebaceous Lipogenesis: A Love–Hate Relationship?

The objective of this narrative review was to check the influence of the human microbiota in the pathogenesis of acne and how the treatment with probiotics as adjuvant or alternative therapy affects the evolution of acne vulgaris. Acne is a chronic inflammatory skin disease involving the pilosebaceous units. The pathogenesis of acne is complex and multifactorial involving genetic, metabolic, and hormonal factors in which both skin and gut microbiota are implicated. Numerous studies have shown the bidirectionality between the intestinal microbiota and skin homeostasis, a communication mainly established by modifying the immune system. Increased data on the mechanisms of action regarding the relevance of Cutibacterium acnes, as well as the importance of the gut–skin axis, are becoming known. Diverse and varied in vitro studies have shown the potential beneficial effects of probiotics in this context. Clinical trials with both topical and oral probiotics are scarce, although they have shown positive results, especially with oral probiotics through the modulation of the intestinal microbiota, generating an anti-inflammatory response and restoring intestinal integrity, or through metabolic pathways involving insulin-like growth factor I (IGF-1). Given the aggressiveness of some standard acne treatments, probiotics should continue to be investigated as an alternative or adjuvant therapy.

ABSTRACTInvestigation of the human microbiome has revealed diverse and complex microbial communities at distinct anatomic sites. The microbiome of the human sebaceous follicle provides a tractable model in which to study its dominant bacterial inhabitant, Propionibacterium acnes, which is thought to contribute to the pathogenesis of the human disease acne. To explore the diversity of the bacteriophages that infect P. acnes, 11 P. acnes phages were isolated from the sebaceous follicles of donors with healthy skin or acne and their genomes were sequenced. Comparative genomic analysis of the P. acnes phage population, which spans a 30-year temporal period and a broad geographic range, reveals striking similarity in terms of genome length, percent GC content, nucleotide identity (>85%), and gene content. This was unexpected, given the far-ranging diversity observed in virtually all other phage populations. Although the P. acnes phages display a broad host range against clinical isolates of P. acnes, two bacterial isolates were resistant to many of these phages. Moreover, the patterns of phage resistance correlate closely with the presence of clustered regularly interspaced short palindromic repeat elements in the bacteria that target a specific subset of phages, conferring a system of prokaryotic innate immunity. The limited diversity of the P. acnes bacteriophages, which may relate to the unique evolutionary constraints imposed by the lipid-rich anaerobic environment in which their bacterial hosts reside, points to the potential utility of phage-based antimicrobial therapy for acne.

Acne is a common chronic inflammatory skin disease in adolescence. The involvement of cosmetically important zones inevitably leads to decrease in our patients' quality of life. This review considers modern methods of skin microbiota analysis, describes the microorganisms' composition in newborns and its changes during growing-up. Cutibacterium acnes (that dominates in the microbiota of skin areas with sebaceous glands) role in acne pathogenesis is described.

Acne is a mutlifactorial disease of the pilosebaceous follicles of the face and upper trunk in which the microorganism, Propionibacterium acnes, is thought to play a central role in the initiation of inflammation. P. acnes is a member of the resident cutaneous microflora and is found in similar numbers on the skin surface and in the pilosebaceous ducts of nonacne subjects, so the disease should not be regarded as an infection. A number of theories have been proposed to explain the role of the organism in the pathogenesis of acne, but conclusive evidence to substantiate any of them is still lacking. However, agents that inhibit the growth of cutaneous propionibacteria are therapeutic, and topical and oral antibiotics remain the most frequently prescribed treatment for acne. More severe cases virtually always respond to therapy with 13-cis retinoic acid. This drug prevents the recurrence of acne in two thirds of patients, but the remaining patients need repeated courses or maintenance on alternative therapies. The highlight of the year under review has been the discovery of bioactive interleukin-1α in the majority of open comedones. The observation that one third of 500 antibiotic-treated acne patients seen in a major dermatology outpatient clinic during 1991 harbor drug-resistant propionibacteria is a cause for concern.

Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands. In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view. An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.

Background: Acne is a prevalent dermatological condition characterized by the blockage of hair follicles and sebaceous glands, leading to the formation of acne. The anaerobe pathogen Cutibacterium acnes (formerly known as Propionibacterium acnes) plays an essential role in the pathogenesis of acne, for which generally antimicrobial treatment is required. Acne is a substantial health concern, and continuing research is being conducted to discover novel and efficacious remedies. The antimicrobial activity of plants has been demonstrated in numerous studies, and they are still targeted organisms in drug development. Studies showing that plants are effective against acne pathogens have also been reported. Methods: The antimicrobial activity of the hydroethanolic extracts prepared from 30 plant species was determined against C. acnes standard strains (C. acnes Scholz and Kilian ATCC 11827 and ATCC 11828) and 30 clinical isolates in our preliminary screening. Since acne is an inflammatory skin disease, the anti-inflammatory effect of six active extracts against C. acnes was determined through the in vitro inhibition of collagenase, lipoxygenase (LOX), hyaluronidase and xanthine oxidase (XO) enzymes. Results: Cotinus coggygria Scop. leaf extract displayed the highest hyaluronidase and collagenase inhibition (79.75% and 52.52%, respectively), while the extract from the aerial parts of Helichrysum arenarium (L.) Moench demonstrated a potent XO inhibitory effect (82.51%). Therefore, these two extracts have been chosen for further studies, and LC/MS-MS was used to determine the phenolic profiles of these extracts. Conclusions: Subsequently, nanoemulgels were formulated with the active extracts to develop a prototype herbal anti-acne product, and characterization studies of the formulations were conducted.

Acne is a chronic inflammatory skin disease that primarily affects adolescents and is attributed to various factors, including hormonal changes, genetic predisposition, and environmental influences. It typically manifests in areas rich in sebaceous glands such as the face, chest, and back. Symptoms of acne can range from mild to severe and may present as pimples, pustules, nodules, cysts, and scarring. The appearance of acne can significantly impact both the physical and mental well-being of patients, potentially leading to feelings of anxiety, depression, and social withdrawal. The pathogenesis of acne is multifaceted involving genetic predisposition as well as environmental factors such as hormonal imbalances, inflammation, abnormal follicular sebaceous unit keratinization, proliferation of follicular microorganisms like Propionibacterium acnes, increased sebum production, and dietary influences. Traditional treatment methods for acne include topical drug therapy, oral drug therapy, photoelectric therapy, and chemical peeling. With ongoing research into the pathogenesis of acne, treatment methods are rapidly evolving with novel antibiotics, probiotics, biological agents, topical anti-androgen drugs, topical vitamin A acid metabolism blockers, antimicrobial peptides, immunotherapy, micro-needling, and micro-needling patches. This article aims to provide a comprehensive review of recent advancements in acne treatment.

Acne vulgaris is an inflammatory disease that develops around the hair follicle. Many are the interconnected etiopathogenic factors involved, among which we can mention the increase in levels of androgen hormones, sebum hypersecretion, follicular hyperkeratosis with microcomedo formation, the proliferation of the bacteria Propionibacterium acnes ( P . acnes ) and the resulting inflammatory response. The way this bacterial growth occurs and how it is connected with the development of the inflammatory process have been themes of many clinical and experimental trials. Modifications in the sebum composition lead to a greater proliferation and differentiation of keratinocytes that obstruct the follicular ostium and favor the formation of comedones. On the other hand, these modifications alter the follicular hydration and facilitate the proliferation of the P . acnes , which not only produces chemotactic factors but also releases lipase that oxidizes the squalene. The oxidized squalene induces the formation of pro-inflammatory cytokines and boosts the innate immunity of keratinocytes and sebocytes, thus generating the inflammatory process. The aim of this study was to review the literature regarding the new concepts on the pathogenesis of acne.

Acne vulgaris is one of the most common skin diseases. The current understanding of acne primarily revolves around inflammatory responses, sebum metabolism disorders, aberrant hormone and receptor expression, colonization by Cutibacterium acnes, and abnormal keratinization of follicular sebaceous glands. Although the precise mechanism of action remains incompletely understood, it is plausible that macrophages exert an influence on these pathological features. Macrophages, as a constituent of the human innate immune system, typically manifest distinct phenotypes across various diseases. It has been observed that the polarization of macrophages toward the M1 phenotype plays a pivotal role in the pathogenesis of acne. In recent years, extensive research on acne has revealed an increasing number of natural remedies exhibiting therapeutic efficacy through the modulation of macrophage polarization. This review investigates the role of cutaneous macrophages, elucidates their potential significance in the pathogenesis of acne, a prevalent chronic inflammatory skin disorder, and explores the therapeutic mechanisms of natural plant products targeting macrophages. Despite these insights, the precise role of macrophages in the pathogenesis of acne remains poorly elucidated. Subsequent investigations in this domain will further illuminate the pathogenesis of acne and potentially offer guidance for identifying novel therapeutic targets for this condition.

Introduction Acne vulgaris is the most common chronic inflammatory skin disease, affecting up to 85% of young adults. It can lead to scarring and significantly reduce the quality of life. Traditionally, acne pathogenesis has been linked to excess sebum, follicular hyperkeratinisation, Cutibacterium acnes colonisation, and inflammation. However, an increasing role has been attributed to changes in the microbiota. Additionally, the gut-skin axis is a modulating factor in acne. Understanding these microbiota interactions offers opportunities for new treatment strategies.Aim of studyThis work aims to evaluate the current evidence regarding the role of the microbiota in the pathogenesis, progression, and treatment of acne vulgaris. Materials and methodsArticles for this review were retrieved from multiple scientific databases, including PubMed, Google Scholar, and other scientific resources. The search methodology incorporated the terms “acne vulgaris” or “acne” AND “microbiome” or “microbiota” or ”gut-skin axis”, along with variations of these terms. ConclusionAcne vulgaris is a complex disease. The skin and gut microbiota play a crucial role in its pathogenesis and treatment. Disruption of Cutibacterium acnes phylotype diversity, alongside its interactions with Staphylococcus epidermidis and Malassezia, contributes to its pathogenesis. Modern therapies, like probiotics and bacteriophages, may provide new treatment opportunities, but further research is needed in this area.

The human skin, especially the sebaceous gland, is a steroidogenic organ similar to the gonads and adrenal cortex, possessing all the enzymes required for steroid sex-hormone synthesis and metabolism. Factors regulating cutaneous steroidogenesis associated with disease status remain largely unknown. We hypothesized that transcription factors involved in sex formation and regulation of steroidogenesis in the classical steroidogenic organs are also expressed in the sebaceous glands. Their possible role in the pathogenesis of acne were investigated. We used reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and Western blotting to analyse the expression of SF-1, WT-1, SRY, SOX-9 and DAX-1 mRNAs and their proteins in cultured human sebocytes and the facial skin of acne patients. The in situ hybridization study showed SOX-9 mRNA mainly localized in basal keratinocytes, the basal layer of the sebaceous glands and eccrine glands. Immortalized human sebaceous gland cells (SZ95) expressed mRNA for SOX-9, WT-1 and DAX-1 but not for SF-1 or SRY. The expression of DAX-1 protein was slightly inhibited by 10(-6) m oestradiol (E2) at 6 h but enhanced by 10(-6) m dihydrotestosterone (DHT) at 48 h. The facial expression of SOX-9 seemed to be higher in the acne-prone male patients, while DAX-1 was stronger in subjects without acne, although both were statistically insignificant. Our findings confirm the expression of some sex-determining genes in human sebaceous glands. Further studies on a larger patient population including the normal controls are needed to elucidate the functional significance of these transcription factors in the pathogenesis of acne.

It is the purpose of this review to extend our understanding of the fibroblast growth factor (FGF) receptor-2b-signaling network in the pathogenesis of acne. A new concept of the role of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases pointing the way to androgen-dependent dermalepithelial FGFR2-signaling in acne. Androgen-mediated upregulation of FGFR2b-signaling in acne-prone skin appears to be involved in the pathogenesis of acne vulgaris. In organotypic skin cultures, keratinocyte-derived interleukin-1alpha stimulated fibroblasts to secrete FGF7 which stimulated FGFR2b-mediated keratinocyte proliferation. Postnatal deletion of FGFR2b in mice resulted in severe sebaceous gland atrophy. The importance of FGFR2b in sebaceous gland physiology is further supported by the mode of action of anti-acne agents which have been proposed to attenuate FGFR2b-signaling. Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity. Insulin-like growth factor-1 (IGF-1), the mediator of growth hormone during puberty, intracts with androgen-dependent FGFR2b-signaling and links androgen- and FGF-mediated signal transduction important in sebaceous gland homeostasis. The search for a follicular defect in the dermalepithelial regulation of growth factor-signaling in acne-prone skin appears to be a most promising approach to clarify the pathogenesis of acne.

Background: The pathogenesis of acne is multifactorial, and it was traditionally believed that four different processes play a decisive role in the development of the disease: the increased production of sebum, changes in keratinization processes leading to the formation of comedones, bacterial colonization of hair follicles by Cutibacterium acnes (C. acnes; formerly called Propionibacterium acnes), and synthesis of pro-inflammatory mediators in the pilosebaceous unit. The role of genetic factors in the development of acne has been repeatedly discussed and continues to be the subject of discussion among scientists. The currently available data from various studies on genetic associations in acne are contradictory, which makes it relevant to address the problem of searching and analyzing the molecular mechanisms of the influence of regulatory genes in the pathogenesis of acne. The aim of this study was to identify and analyze SNPs in the regulatory genes (GATA1, GATA2, GATA2-AS1 [GATA2 Antisense RNA 1], NFKB2, NFKBIA, and NFKB1) in patients with severe acne. Methods and Results: A prospective, open, non-randomized, single-center comparative study was conducted between 2017-2020. The study included 50 (29 men and 21 women) patients (the main group [MG]) with severe acne aged from 15 to 46 years (the median age of 23.2 years) and 20 (13 men and 7 women) apparently healthy individuals (the comparison group [CG]) aged from 16 to 40 years (the median age of 19.4 years). Molecular genetic diagnostics was performed using high-throughput DNA sequencing—next-generation sequencing (NGS). The results of our study made it possible to identify SNPs in regulatory genes (GATA1, GATA2, GATA2-AS1 [GATA2 Antisense RNA 1], NFKB2, NFKBIA, and NFKB1) associated with the development of severe acne. Conclusion: The revealed SNPs within the GATA1, GATA2, GATA2-AS1 [GATA2 Antisense RNA 1], NFKB2, NFKBIA, and NFKB1 genes in patients with severe acne probably indicate the involvement of regulatory transcription factors in the pathogenesis of acne.

Inflammatory skin diseases include a variety of skin diseases, such as seborrheic dermatitis, acne, atopic dermatitis, psoriasis and so on, which are more common and tend to have a significant impact on patients' quality of life. Inflammatory skin diseases often result in physical or psychological distress; however, the pathogenesis of these diseases have not been clearly elucidated. Many factors are involved in the pathogenesis of inflammatory skin diseases, including heredity, environment, immunity, epidermal barrier, mental disorders, infection and so on. In recent years, skin microbiota has been shown to play an important role in inflammatory skin diseases. To elaborate on the specific mechanisms of inflammatory skin diseases induced by microbiota dysbiosis. We introduce the function and influence of skin microbiota in inflammatory skin diseases from the following aspects: Immunity, epigenetics, epidermal barrier and treatment. Skin microbiota can affect many aspects of the host, such as Immunity, epigenetics, epidermal barrier, and it plays an important role in the pathogenesis of inflammatory skin diseases. Skin microbiota is extremely important for maintaining the health of skin and the dysbiosis of skin microbiota is an important pathogenesis of inflammatory skin diseases.