Concept: Acne vulgaris
Skin barrier structure and function is essential to human health. Hitherto unrecognized functions of epidermal keratinocytes show that the skin plays an important role in adapting whole-body physiology to changing environments, including the capacity to produce a wide variety of hormones, neurotransmitters and cytokine that can potentially influence whole-body states, and quite possibly, even emotions. Skin microbiota play an integral role in the maturation and homeostatic regulation of keratinocytes and host immune networks with systemic implications. As our primary interface with the external environment, the biodiversity of skin habitats is heavily influenced by the biodiversity of the ecosystems in which we reside. Thus, factors which alter the establishment and health of the skin microbiome have the potential to predispose to not only cutaneous disease, but also other inflammatory non-communicable diseases (NCDs). Indeed, disturbances of the stratum corneum have been noted in allergic diseases (eczema and food allergy), psoriasis, rosacea, acne vulgaris and with the skin aging process. The built environment, global biodiversity losses and declining nature relatedness are contributing to erosion of diversity at a micro-ecological level, including our own microbial habitats. This emphasises the importance of ecological perspectives in overcoming the factors that drive dysbiosis and the risk of inflammatory diseases across the life course.
Studies have emphasized the importance of disease-associated microorganisms in perturbed communities, however, the protective roles of commensals are largely under recognized and poorly understood. Using acne as a model disease, we investigated the determinants of the overall virulence property of the skin microbiota when disease- and health-associated organisms coexist in the community. By ultra-deep metagenomic shotgun sequencing, we revealed higher relative abundances of propionibacteria and Propionibacterium acnes phage in healthy skin. In acne patients, the microbiome composition at the species level and at P. acnes strain level was more diverse than in healthy individuals, with enriched virulence-associated factors and reduced abundance of metabolic synthesis genes. Based on the abundance profiles of the metagenomic elements, we constructed a quantitative prediction model, which classified the clinical states of the host skin with high accuracy in both our study cohort (85%) and an independent sample set (86%). Our results suggest that the balance between metagenomic elements, not the mere presence of disease-associated strains, shapes the overall virulence property of the skin microbiota. This study provides new insights into the microbial mechanism of acne pathogenesis and suggests probiotic and phage therapies as potential acne treatments to modulate the skin microbiota and to maintain skin health.
- Clinical, cosmetic and investigational dermatology
- Published over 5 years ago
Acne vulgaris, an epidemic inflammatory skin disease of adolescence, is closely related to Western diet. Three major food classes that promote acne are: 1) hyperglycemic carbohydrates, 2) milk and dairy products, 3) saturated fats including trans-fats and deficient ω-3 polyunsaturated fatty acids (PUFAs). Diet-induced insulin/insulin-like growth factor (IGF-1)-signaling is superimposed on elevated IGF-1 levels during puberty, thereby unmasking the impact of aberrant nutrigenomics on sebaceous gland homeostasis. Western diet provides abundant branched-chain amino acids (BCAAs), glutamine, and palmitic acid. Insulin and IGF-1 suppress the activity of the metabolic transcription factor forkhead box O1 (FoxO1). Insulin, IGF-1, BCAAs, glutamine, and palmitate activate the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the key regulator of anabolism and lipogenesis. FoxO1 is a negative coregulator of androgen receptor, peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor-α, and sterol response element binding protein-1c (SREBP-1c), crucial transcription factors of sebaceous lipogenesis. mTORC1 stimulates the expression of PPARγ and SREBP-1c, promoting sebum production. SREBP-1c upregulates stearoyl-CoA- and Δ6-desaturase, enhancing the proportion of monounsaturated fatty acids in sebum triglycerides. Diet-mediated aberrations in sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate. Free palmitate functions as a “danger signal,” stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte proliferation. Oleate stimulates P. acnes adhesion, keratinocyte proliferation, and comedogenesis via interleukin-1α release. Thus, diet-induced metabolomic alterations promote the visible sebofollicular inflammasomopathy acne vulgaris. Nutrition therapy of acne has to increase FoxO1 and to attenuate mTORC1/SREBP-1c signaling. Patients should balance total calorie uptake and restrict refined carbohydrates, milk, dairy protein supplements, saturated fats, and trans-fats. A paleolithic-like diet enriched in vegetables and fish is recommended. Plant-derived mTORC1 inhibitors and ω-3-PUFAs are promising dietary supplements supporting nutrition therapy of acne vulgaris.
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.
Epidemiological studies suggest that chocolate increases the incidence and severity of acne. Here we demonstrate that chocolate consumption primes human blood mononuclear cells from volunteers to release more interleukin-1β (IL-1β) and IL-10 upon stimulation with Propionibacterium acne or Staphylcoccus aureus, the two microorganisms involved in the pathogenesis of acne. In contrast, production of the Th17-derived cytokine IL-22 was inhibited by chocolate. Modulation of inflammation could represent an important mechanism through which chocolate consumption influences acne.
The endocannabinoid system (ECS) regulates multiple physiological processes, including cutaneous cell growth and differentiation. Here, we explored the effects of the major nonpsychotropic phytocannabinoid of Cannabis sativa, (-)-cannabidiol (CBD), on human sebaceous gland function and determined that CBD behaves as a highly effective sebostatic agent. Administration of CBD to cultured human sebocytes and human skin organ culture inhibited the lipogenic actions of various compounds, including arachidonic acid and a combination of linoleic acid and testosterone, and suppressed sebocyte proliferation via the activation of transient receptor potential vanilloid-4 (TRPV4) ion channels. Activation of TRPV4 interfered with the prolipogenic ERK1/2 MAPK pathway and resulted in the downregulation of nuclear receptor interacting protein-1 (NRIP1), which influences glucose and lipid metabolism, thereby inhibiting sebocyte lipogenesis. CBD also exerted complex antiinflammatory actions that were coupled to A2a adenosine receptor-dependent upregulation of tribbles homolog 3 (TRIB3) and inhibition of the NF-κB signaling. Collectively, our findings suggest that, due to the combined lipostatic, antiproliferative, and antiinflammatory effects, CBD has potential as a promising therapeutic agent for the treatment of acne vulgaris.
Acne vulgaris is a chronic inflammatory disease with a complex pathogenesis that affects predominantly adolescents. The aim of the study was to investigate the interrelations between the presence of acne and several variables associated with somatic growth, pubertal maturation, and environmental conditions (altitude and regions of residence). A population sample of 6,200 clinically healthy boys (0-19 years) was examined and the presence of acne was determined. Height, weight, testicular volumes, penile length and circumference, as well as pubic hair were also measured. The prevalence of moderate and severe acne in the whole group was 7.74 %, while in the age group 12-19 years, it was 19.31 %. Twelve-15-year-old boys with acne were taller and heavier than the ones without. They also had increased penile length and circumference as well as larger testicular volumes. Somatometric and pubertal characteristics of 17-19-year-old boys with and without acne were similar. The prevalence of the disease did not differ between the rural and urban inhabitants. However, the acne frequency decreased with the increasing of the altitude where the boys lived. Conclusions: Our results showed that the development of acne vulgaris in male adolescents was associated with an intensive growth and pubertal maturation, while obesity per se did not play an important role. Of particular interest was the association between the prevalence of acne and the altitude of residence.
Abstract Background The oral tetracyclines, especially minocycline hydrochloride, are often used as an effective treatment for perioral dermatitis, however they are sometimes difficult to use because of the side effects, especially in children. Objective The effectiveness of β-lactam antibiotics was evaluated in three cases of perioral dermatitis. Methods Three Japanese patients with perioral dermatitis were treated with cefcapene pivoxil hydrochloride hydrate per os 100 to 300 mg per day. They were one girl (age 10) and two adult women (age 32, 37). One of the adult patients had a past history of Meniere’s disease and the other had had a side effect, vertigo, from minocycline hydrochloride treatment. The presence of fusobacteria before and after the treatment was examined using the tape-stripping toluidine blue method. Results These patients showed the improvement in 1 to 2 weeks and were much improved or cured after 2 to 5 weeks. No side effects were found during the treatment. Fusobacteria were positive before treatment but became negative after the treatment in all of them. Conclusion β-lactam antibiotics might be a useful treatment for perioral dermatitis, especially in cases who cannot take tetracyclines.
Comparison of Fractional Erbium-Doped Yttrium Aluminum Garnet and Carbon Dioxide Lasers in Resurfacing of Atrophic Acne Scars in Asians.
- Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]
- Published about 8 years ago
BACKGROUND: The efficacy of fractional erbium-doped yttrium aluminum garnet (Er:YAG) and carbon dioxide (CO(2) ) lasers are well substantiated. OBJECTIVE: To compare the efficacy and safety of these two laser systems for treatment of atrophic scars in dark-skinned patients. MATERIALS AND METHODS: Twenty-four subjects with acne scars were randomly treated with a fractional Er:YAG laser on one side and a fractional CO(2) laser on the other side. All subjects received two treatments with a 2-month interval. Objective and subjective assessments were obtained at baseline and 1, 3, and 6 months after the final treatment. RESULTS: At the 6 month follow up, 55% and 65% of Er: YAG and CO(2) laser sites, respectively, were graded as having more than 50% improvement of scars. Improvement progressed significantly from 1- to 6-month follow-up (p < .001). There was no significant difference in clinical improvement between the two systems at 1- (p = .90), 3- (p = .54), and 6-month (p = .87) follow-up. Reduction in scar volume corresponded to clinical evaluation. CONCLUSIONS: Fractional Er:YAG and CO(2) lasers provided comparable outcomes of scar treatment, but fractional CO(2) laser was associated with greater treatment discomfort.
Autologous Platelet Rich Plasma: Topical Versus Intradermal After Fractional Ablative Carbon Dioxide Laser Treatment of Atrophic Acne Scars
- Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]
- Published about 7 years ago
A proposal has recently been made regarding the potential adjuvant use of platelet-rich plasma (PRP) with fractional carbon dioxide laser (FCL) for the correction of acne scars.