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Archives of Dermatological Research Jul 2019Acne vulgaris is a cutaneous chronic inflammatory disorder with complex pathogenesis. Four factors play vital roles in acne pathophysiology: hyperseborrhea and... (Review)
Review
Acne vulgaris is a cutaneous chronic inflammatory disorder with complex pathogenesis. Four factors play vital roles in acne pathophysiology: hyperseborrhea and dysseborrhea, altered keratinization of the pilosebaceous duct, Cutibacterium acnes (C. acnes) and inflammation. The main hormones responsible for the development of acne vulgaris include androgens, insulin and insulin-like growth factor-1. Other factors involved in this process are corticotropin-releasing hormone, α-melanocyte-stimulating hormone and substance P. Wnt/β-catenin signaling pathway, phosphoinositide 3-kinase (PI3K)/Akt pathway, mitogen-activated protein kinase pathway, adenosine 5'-monophosphate-activated protein kinase pathway and nuclear factor kappa B pathway participate in the modulation of sebocyte, keratinocyte and inflammatory cell (e.g. lymphocytes, monocytes, macrophages, neutrophils) activity. Among all the triggers and pathways mentioned above, IGF-1-induced PI3K/Akt/Forkhead box protein O1/mammalian target of rapamycin (mTOR) C1 pathway is the most important signaling responsible for acne pathogenesis. Commonly used anti-acne agents include retinoids, benzoyl peroxide, antibiotics and hormonal agents (e.g. spironolactone, combination oral contraceptive and flutamide). New approaches including peroxisome proliferator-activated receptor γ modifier, melanocortin receptor antagonists, epigallocatechin-3-gallate, metformin, olumacostat glasaretil, stearoyl-CoA desaturase inhibitor omiganan pentahydrochloride, KPT, afamelanotide, apremilast and biologics have been developed as promising treatments for acne vulgaris. Although these anti-acne agents have various pharmacological effects against the diverse pathogenesis of acne, all of them have a synergistic mode of action, the attenuation of Akt/mTORC1 signaling and enhancement of p53 signal transduction. In addition to drug therapy, diet with no hyperglycemic carbohydrates, no milk and dairy products is also beneficial for treatment of acne.
Topics: Acne Vulgaris; Anti-Bacterial Agents; Dairy Products; Dermatologic Agents; Dietary Carbohydrates; Drug Synergism; Humans; Propionibacterium acnes; Sebaceous Glands; Sebum; Signal Transduction
PubMed: 30859308
DOI: 10.1007/s00403-019-01908-x -
Cell May 2016Biogeography and individuality shape the structural and functional composition of the human skin microbiome. To explore these factors' contribution to skin microbial...
Biogeography and individuality shape the structural and functional composition of the human skin microbiome. To explore these factors' contribution to skin microbial community stability, we generated metagenomic sequence data from longitudinal samples collected over months and years. Analyzing these samples using a multi-kingdom, reference-based approach, we found that despite the skin's exposure to the external environment, its bacterial, fungal, and viral communities were largely stable over time. Site, individuality, and phylogeny were all determinants of stability. Foot sites exhibited the most variability; individuals differed in stability; and transience was a particular characteristic of eukaryotic viruses, which showed little site-specificity in colonization. Strain and single-nucleotide variant-level analysis showed that individuals maintain, rather than reacquire, prevalent microbes from the environment. Longitudinal stability of skin microbial communities generates hypotheses about colonization resistance and empowers clinical studies exploring alterations observed in disease states.
Topics: Bacteria; Bacterial Physiological Phenomena; DNA Viruses; Fungi; Homeostasis; Humans; Microbiota; Propionibacterium acnes; Skin; Skin Physiological Phenomena; Symbiosis; Virus Physiological Phenomena; Viruses
PubMed: 27153496
DOI: 10.1016/j.cell.2016.04.008 -
Science Translational Medicine Jun 2015Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood....
Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood. Using acne as a disease model, we aimed to understand the molecular response of the skin microbiota to host metabolite signaling in disease pathogenesis. Metatranscriptomic analysis revealed that the transcriptional profiles of the skin microbiota separated acne patients from healthy individuals. The vitamin B12 biosynthesis pathway in the skin bacterium Propionibacterium acnes was significantly down-regulated in acne patients. We hypothesized that host vitamin B12 modulates the activities of the skin microbiota and contributes to acne pathogenesis. To test this hypothesis, we analyzed the skin microbiota in healthy subjects supplemented with vitamin B12. We found that the supplementation repressed the expression of vitamin B12 biosynthesis genes in P. acnes and altered the transcriptome of the skin microbiota. One of the 10 subjects studied developed acne 1 week after vitamin B12 supplementation. To further understand the molecular mechanism, we revealed that vitamin B12 supplementation in P. acnes cultures promoted the production of porphyrins, which have been shown to induce inflammation in acne. Our findings suggest a new bacterial pathogenesis pathway in acne and provide one molecular explanation for the long-standing clinical observation that vitamin B12 supplementation leads to acne development in a subset of individuals. Our study discovered that vitamin B12, an essential nutrient in humans, modulates the transcriptional activities of skin bacteria, and provided evidence that metabolite-mediated interactions between the host and the skin microbiota play essential roles in disease development.
Topics: Acne Vulgaris; Adult; Case-Control Studies; Dietary Supplements; Down-Regulation; Female; Gene Expression Profiling; Humans; Male; Metabolic Networks and Pathways; Microbiota; Models, Biological; Operon; Porphyrins; Propionibacterium acnes; Skin; Transcription, Genetic; Transcriptome; Vitamin B 12; Young Adult
PubMed: 26109103
DOI: 10.1126/scitranslmed.aab2009 -
Nature Oct 2014The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial...
The varied topography of human skin offers a unique opportunity to study how the body's microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal and viral communities, which showed not only site specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalogue, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes and strain tracking, and defines the dual influence of biogeography and individuality on microbial composition and function.
Topics: Bacteriophages; Female; Genome, Bacterial; Genome, Fungal; Genome, Viral; Genomics; Healthy Volunteers; Humans; Male; Metagenome; Phylogeny; Propionibacterium acnes; Skin; Staphylococcus epidermidis; Symbiosis
PubMed: 25279917
DOI: 10.1038/nature13786 -
Current Problems in Dermatology 2018Acne is based on a complex, multifactorial pathophysiology beginning with a microcomedo. Comedogenesis involves follicular hyperproliferation and disturbed... (Review)
Review
Acne is based on a complex, multifactorial pathophysiology beginning with a microcomedo. Comedogenesis involves follicular hyperproliferation and disturbed keratinization, hyperseborrhea and hyperplasia of sebaceous glands as well as disturbances in skin microbiome. Acne is treated with antibiotics, retinoids, keratolytics, hormonal and anti-inflammatory agents. Efficacy and side effects of given medications are well known. The uppermost layer of the stratum corneum is acidic. The low pH provides protection by slowing down the growth of some bacteria. Increase of skin surface pH leads to impaired barrier function, disturbances in skin microbiome and inflammation. Acne-predisposed skin is in a constant state of subclinical inflammation. Subclinical inflammation may be linked to changes in skin surface pH and disturbances of the stratum corneum, allowing microorganisms to stimulate the production of pro-inflammatory cytokines. Here, based on the current literature, the possible link between the skin surface pH, epidermal barrier function and acne is reviewed.
Topics: Acne Vulgaris; Aging; Animals; Female; Humans; Hydrogen-Ion Concentration; Male; Propionibacterium acnes; Sex Characteristics; Skin; Skin Pigmentation
PubMed: 30130780
DOI: 10.1159/000489525 -
Clinical and Experimental Dermatology Dec 2020Current acne treatments present several limitations, posing the need for new effective therapies for long-term administration for recalcitrant or relapsing acne. Key... (Review)
Review
Current acne treatments present several limitations, posing the need for new effective therapies for long-term administration for recalcitrant or relapsing acne. Key players in acne that may emerge as targets for future acne treatments include the cutaneous loss of diversity of Cutibacterium (formerly Propionibacterium) acnes phylotypes and the insulin-like growth factor-1 signalling pathway. New data about the loss of diversity of microbiota in acne provides the rationale for the potential use of oral or topical probiotics. Another therapeutic approach to modulate the microbiota could be topical formulation of C. acnes bacteriophages to target specifically the pathogenic 'acnegenic' C. acnes phylotypes. Insulin-sensitizing agents such as metformin, myo-inositol and d-chiro-inositol represent promising agents, but to date there have been only limited studies and much heterogeneity in the methods of assessing acne efficacy outcomes. Moving towards a holistic approach for patients with acne is the future, by taking into account both internal and external factors, such as pollution, stress, acne family history, age, smoking habits and diet, and addressing quality of life and the psychological impact of acne.
Topics: Acne Vulgaris; Administration, Oral; Administration, Topical; Age Factors; Environmental Pollution; Female; Humans; Insulin Resistance; Insulin-Like Growth Factor I; Life Style; Male; Medical History Taking; Microbiota; Probiotics; Propionibacterium acnes; Quality of Life; Secondary Prevention; Stress, Psychological
PubMed: 32412672
DOI: 10.1111/ced.14239 -
Journal of the European Academy of... Apr 2024Acne vulgaris is a chronic inflammatory skin disease with a complex pathogenesis. Traditionally, the primary pathophysiologic factors in acne have been thought to be:... (Review)
Review
Acne vulgaris is a chronic inflammatory skin disease with a complex pathogenesis. Traditionally, the primary pathophysiologic factors in acne have been thought to be: (1) altered sebum production, (2) inflammation, (3) excess keratinization and (4) colonization with the commensal Cutibacterium acnes. However, the role of C. acnes has been unclear, since virtually all adults have C. acnes on their skin yet not all develop acne. In recent years, understanding of the role of C. acnes has expanded. It is still acknowledged to have an important place in acne pathogenesis, but evidence suggests that an imbalance of individual C. acnes phylotypes and an alteration of the skin microbiome trigger acne. In addition, it is now believed that Staphylococcus epidermidis is also an actor in acne development. Together, C. acnes and S. epidermidis maintain and regulate homeostasis of the skin microbiota. Antibiotics, which have long been a staple of acne therapy, induce cutaneous dysbiosis. This finding, together with the long-standing public health edict to spare antibiotic use when possible, highlights the need for a change in acne management strategies. One fertile direction of study for new approaches involves dermocosmetic products that can support epidermal barrier function and have a positive effect on the skin microbiome.
Topics: Humans; Acne Vulgaris; Skin; Microbiota; Dermatitis; Dysbiosis; Anti-Bacterial Agents; Propionibacterium acnes
PubMed: 37777343
DOI: 10.1111/jdv.19540 -
Trends in Microbiology Apr 2023
Topics: Propionibacterium acnes; Skin
PubMed: 36328874
DOI: 10.1016/j.tim.2022.10.006 -
Current Drug Metabolism 2015Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The... (Review)
Review
Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes-induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases.
Topics: Acne Vulgaris; Animals; Bacterial Vaccines; Corynebacterium; Humans; Immunotherapy; Propionibacterium acnes
PubMed: 26264195
DOI: 10.2174/1389200216666150812124801 -
Joint Bone Spine Mar 2018Overt infection by Propionibacterium acnes is lacking in many SAPHO syndromes, and antibiotics have only a transient and incomplete effect, either in SAPHO syndrome or... (Review)
Review
Overt infection by Propionibacterium acnes is lacking in many SAPHO syndromes, and antibiotics have only a transient and incomplete effect, either in SAPHO syndrome or acne. As several auto-inflammatory bone disorders sharing overproduction of IL-1β can mimic SAPHO, this syndrome could partly depend on genetically encoded overproduction of IL-1β. However, cyclic intracellular infections, mostly by P. acnes, can contribute to the enhanced IL-1β release by some skin cells, and probably by bone cells. P. acnes is indeed a powerful trigger of NLRP3-inflammasome activation and IL-1β, leading to osteitis and enhanced mesenchymal cells differentiation in osteoblasts. Recent advances in the understanding of acne suggest that first steps of this disorder are not driven by P. acnes, but by a relative deficiency of FoxO1 within the nucleus of sebaceous cells. A similar defect of FoXO1 in bone cells should also be sought in SAPHO, since repression of FoxO1 gene is found in lesional psoriasis skin, and is associated with an increased number of osteoblasts and high bone mass in mice. FoxO1 selectively promotes IL-1β production, so that its downregulation could help some P. acnes t escape innate immunity and persist in a latent state in bone cells, including mesenchymal stem cells. However, P. acnes itself possibly contributes to FoxO1 downregulation, like H. pylori infection which induces nuclear inactivation of FoxO1 in human gastric cells to slow down autophagic clearance. As bisphosphonates, which often improve SAPHO syndromes, enhance autophagy, it may be worth testing whether their combination with antibiotics is synergistic in SAPHO syndromes.
Topics: Acne Vulgaris; Acquired Hyperostosis Syndrome; Autophagy; Disease Progression; Down-Regulation; Female; Forkhead Box Protein O1; Humans; Interleukin-1; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Prognosis; Propionibacterium acnes; Risk Assessment; Severity of Illness Index
PubMed: 28499891
DOI: 10.1016/j.jbspin.2017.04.010