Association between Environmental Exposure to Multiclass Organic Pollutants and Sex Steroid Hormone Levels in Women of Reproductive Age.

Organic pollutant exposure may alter sex steroid hormone levels in both animals and humans, but studies on mixture effects have been lacking and mainly limited to persistent organic pollutants, with few hormones being investigated. Moreover, measurements from a single blood or urine sample may not be able to reflect long-term status. Using hair analysis, here, we evaluated the relationship between multiclass organic pollutants and sex steroid hormones in 196 healthy Chinese women aged 25-45 years. Associations with nine sex steroid hormones, including progesterone, androstenedione (AD), testosterone (T), estrone (E1), and 17ß-estradiol (E2), and eight related hormone ratios were explored on 54 pollutants from polychlorinated biphenyl (PCB), pesticide, and bisphenol families using stability-based Lasso regression analysis. Our results showed that each hormone was associated with a mixture of at least 10 examined pollutants. In particular, hair E2 concentration was associated with 19 pollutants, including γ-hexachlorocyclohexane, propoxur, permethrin, fipronil, mecoprop, prochloraz, and carbendazim. There were also associations between pollutants and hormone ratios, with pentachlorophenol, dimethylthiophosphate, 3-phenoxybenzoic acid, and flusilazole being related to both E1/AD and E2/T ratios. Our results suggest that exposure to background levels of pesticides PCB180 and bisphenol S may affect sex steroid hormone homeostasis among women of reproductive age.

Human pollution exposure correlates with accelerated ultrastructural degradation of hair fibers.

Exposure to pollution is a known risk factor for human health. While correlative studies between exposure to pollutants such as polycyclic aromatic hydrocarbons (PAHs) and human health exist, and while in vitro studies help to establish a causative connection, in vivo comparisons of exposed and nonexposed human tissue are scarce. Here, we use human hair as a model matrix to study the correlation of PAH pollution with microstructural changes over time. Two hundred four hair samples from 2 Chinese cities with distinct pollution exposure were collected, and chromatographic-mass spectrometry was used to quantify the PAH-exposure profiles of each individual sample. This allowed us to define a group of less contaminated hair samples as well as a more contaminated group. Using transmission electron microscopy (TEM) together with quantitative image analysis and blind scoring of 82 structural parameters, we find that the speed of naturally occurring hair-cortex degradation and cuticle delamination is increased in fibers with increased PAH concentrations. Treating nondamaged hair fibers with ultraviolet (UV) irradiation leads to a more pronounced cortical damage especially around melanosomes of samples with higher PAH concentrations. Our study shows the detrimental effect of physiological concentrations of PAH together with UV irradiation on the hair microstructure but likely can be applied to other human tissues.

A jasmonic acid derivative improves skin healing and induces changes in proteoglycan expression and glycosaminoglycan structure.

BACKGROUND: Jasmonates are plant hormones that exhibit anti-cancer and anti-inflammatory properties and have therefore raised interest for human health applications. The molecular basis of these activities remains poorly understood, although increasing evidence suggests that a variety of mechanisms may be involved. Recently, we have reported that a jasmonate derivative (JAD) displayed anti-aging effects on human skin by inducing extracellular matrix (ECM) remodeling. Based on this observation, we have investigated here the effects of JAD on proteoglycans and glycosaminoglycan (GAG) polysaccharides, which are major cell-surface/ECM components and are involved in a multitude of biological processes. In parallel, we have examined the ability of JAD to promote growth factor activities and improve skin wound healing. METHODS: Proteoglycan expression was analyzed on epidermal primary keratinocytes and reconstituted skin epidermis, using electron/immunofluorescence microscopy, western blotting and flow cytometry. GAG composition was determined by disaccharide analysis. Finally, biological activities of JAD were assessed in cellulo, in FGF-7 induced migration/proliferation assays, as well as in vivo, using a suction blister model performed on 24 healthy volunteers. RESULTS: JAD was found to induce expression of major skin proteoglycans and to induce subtle changes in GAG structure. In parallel, we showed that JAD promoted FGF-7 and improved skin healing by accelerating epithelial repair in vivo. CONCLUSION: This study highlights JAD as a promising compound for investigating GAG structure-function relationships and for applications in skin cosmetic /corrective strategies. GENERAL SIGNIFICANCE: We propose here a novel mechanism, by which jasmonate derivatives may elicit biological activities in mammals.

Deviance residuals-based sparse PLS and sparse kernel PLS regression for censored data.

MOTIVATION: A vast literature from the past decade is devoted to relating gene profiles and subject survival or time to cancer recurrence. Biomarker discovery from high-dimensional data, such as transcriptomic or single nucleotide polymorphism profiles, is a major challenge in the search for more precise diagnoses. The proportional hazard regression model suggested by Cox (1972), to study the relationship between the time to event and a set of covariates in the presence of censoring is the most commonly used model for the analysis of survival data. However, like multivariate regression, it supposes that more observations than variables, complete data, and not strongly correlated variables are available. In practice, when dealing with high-dimensional data, these constraints are crippling. Collinearity gives rise to issues of over-fitting and model misidentification. Variable selection can improve the estimation accuracy by effectively identifying the subset of relevant predictors and enhance the model interpretability with parsimonious representation. To deal with both collinearity and variable selection issues, many methods based on least absolute shrinkage and selection operator penalized Cox proportional hazards have been proposed since the reference paper of Tibshirani. Regularization could also be performed using dimension reduction as is the case with partial least squares (PLS) regression. We propose two original algorithms named sPLSDR and its non-linear kernel counterpart DKsPLSDR, by using sparse PLS regression (sPLS) based on deviance residuals. We compared their predicting performance with state-of-the-art algorithms on both simulated and real reference benchmark datasets. RESULTS: sPLSDR and DKsPLSDR compare favorably with other methods in their computational time, prediction and selectivity, as indicated by results based on benchmark datasets. Moreover, in the framework of PLS regression, they feature other useful tools, including biplots representation, or the ability to deal with missing data. Therefore, we view them as a useful addition to the toolbox of estimation and prediction methods for the widely used Cox's model in the high-dimensional and low-sample size settings. AVAILABILITY AND IMPLEMENTATION: The R-package plsRcox is available on the CRAN and is maintained by Frédéric Bertrand. http://cran.r-project.org/web/packages/plsRcox/index.html. CONTACT: pbastien@rd.loreal.com or fbertran@math.unistra.fr. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A chronic pro-inflammatory environment contributes to the physiopathology of actinic lentigines.

Actinic lentigines (AL) or age spots, are skin hyperpigmented lesions associated with age and chronic sun exposure. To better understand the physiopathology of AL, we have characterized the inflammation response in AL of European and Japanese volunteers. Gene expression profile showed that in both populations, 10% of the modulated genes in AL versus adjacent non lesional skin (NL), i.e. 31 genes, are associated with inflammation/immune process. A pro-inflammatory environment in AL is strongly suggested by the activation of the arachidonic acid cascade and the plasmin pathway leading to prostaglandin production, along with the decrease of anti-inflammatory cytokines and the identification of inflammatory upstream regulators. Furthermore, in line with the over-expression of genes associated with the recruitment and activation of immune cells, immunostaining on skin sections revealed a significant infiltration of CD68+ macrophages and CD4+ T-cells in the dermis of AL. Strikingly, investigation of infiltrated macrophage subsets evidenced a significant increase of pro-inflammatory CD80+/CD68+ M1 macrophages in AL compared to NL. In conclusion, a chronic inflammation, sustained by pro-inflammatory mediators and infiltration of immune cells, particularly pro-inflammatory M1 macrophages, takes place in AL. This pro-inflammatory loop should be thus broken to normalize skin and improve the efficacy of age spot treatment.

Glucocorticoid hormones in relation to environmental exposure to bisphenols and multiclass pesticides among middle aged-women: Results from hair analysis.

Bisphenols and pesticides have been shown to alter circulating glucocorticoids levels in animals, but there is limited human data. Moreover, measurements from biological fluids may not be able to reflect long-term status of non-persistent pollutants and glucocorticoids due to the high variability in their levels. Using hair analysis, we examined the associations between glucocorticoid hormones and environmental exposure to multi-class organic pollutants among a healthy female population aged 25-45 years old. Concentrations of four glucocorticoids, four polychlorinated biphenyl congeners (PCBs), seven polybrominated diphenyl ether congeners (PBDEs), two bisphenols and 140 pesticides and their metabolites were measured in hair samples collected from 196 Chinese women living in urban areas. Due to the low detection frequency of some pollutants, associations were explored only on 54 pollutants, i.e. PCB 180, bisphenol A, bisphenol S and 51 pesticides and their metabolites. Using stability-based Lasso regression, there were associations of cortisol, tetrahydrocortisol, cortisone, and tetrahydrocortisone with 14, 10, 13 and 17 biomarkers of exposure to pollutants, respectively, with bisphenol S, p,p'-dichlorodiphenyldichloroethylene, diethyl phosphate, 3,5,6-trichloro-2-pyridinol, thiamethoxam, imidacloprid, fipronil, tebuconazole, trifluralin, pyraclostrobin and 1-(3,4-dichlorophenyl)-3-methylurea being associated with at least three of the four hormones. There were also associations between cortisone/cortisol molar ratio and pollutants, namely dimethyl phosphate, 3-methyl-4-nitrophenol, carbofuran, λ-cyhalothrin, permethrin, fipronil, flusilazole, prometryn and fenuron. Some of these relationships were confirmed by single-pollutant linear regression analyses. Overall, our results suggest that background level of exposure to bisphenols and currently used pesticides may interfere with the glucocorticoid homeostasis in healthy women.

Skin microbiome differentiates into distinct cutotypes with unique metabolic functions upon exposure to polycyclic aromatic hydrocarbons.

BACKGROUND: The effects of air pollutants, particularly polycyclic aromatic hydrocarbons (PAHs), on the skin microbiome remain poorly understood. Thus, to better understand the interplay between air pollutants, microbiomes, and skin conditions, we applied metagenomics and metabolomics to analyze the effects of PAHs in air pollution on the skin microbiomes of over 120 subjects residing in two cities in China with different levels of air pollution. RESULTS: The skin microbiomes differentiated into two cutotypes (termed 1 and 2) with distinct taxonomic, functional, resistome, and metabolite compositions as well as skin phenotypes that transcended geography and host factors. High PAH exposure was linked to dry skin and cutotype 2, which was enriched with species with potential biodegradation functions and had reduced correlation network structure integrity. The positive correlations identified between dominant taxa, key functional genes, and metabolites in the arginine biosynthesis pathway in cutotype 1 suggest that arginine from bacteria contributes to the synthesis of filaggrin-derived natural moisturizing factors (NMFs), which provide hydration for the skin, and could explain the normal skin phenotype observed. In contrast, no correlation with the arginine biosynthesis pathway was observed in cutotype 2, which indicates the limited hydration functions of NMFs and explains the observed dry skin phenotype. In addition to dryness, skin associated with cutotype 2 appeared prone to other adverse conditions such as inflammation. CONCLUSIONS: This study revealed the roles of PAHs in driving skin microbiome differentiation into cutotypes that vary extensively in taxonomy and metabolic functions and may subsequently lead to variations in skin-microbe interactions that affect host skin health. An improved understanding of the roles of microbiomes on skin exposed to air pollutants can aid the development of strategies that harness microbes to prevent undesirable skin conditions. Video Abstract.

Combining the use of two non-invasive instruments to confirm that a formula can improve skin luminance while respecting constitutive melanogenesis.

INTRODUCTION: Skin radiance products achieve perceivable benefits with different sort of mechanism of action. AIMS: To use two non-invasive instrumental devices to evaluate the effectiveness of a cosmetic formula designed to improve skin reflectance while respecting skin integrity. PATIENTS AND METHODS: Subjects (N = 43) aged 18-50 years old had healthy skin of phototype V-VI and Individual Typology Angle between -10° and -50°. The treatment was applied twice weekly for 4 weeks on a delineated area of the back, and an adjacent area was left untreated. Instrumental and clinical scoring assessments of treated and untreated skin were performed at baseline and Day 26. RESULTS: Between baseline and Day 26, reflectance (Delta L*) increased by 1.27 points and was considered as clinically relevant. Dermatologist clinical scoring of radiance significantly improved from 2.6 to 3.6 after 4 weeks of treatment and the Skin Color Chart Clarity level significantly decreased from a score of 15.5 to 14.3, representing a skin reflectance improvement. Conversely, the change between baseline and Day 26 in Mexameter Melanin Density was not clinically different for treated skin versus untreated skin (difference of 2.54). At Day 26, changes from baseline for Mexameter Melanin Density and Delta L* parameters appeared to be uncorrelated (r = -0.036). CONCLUSIONS: This combination of two non-invasive devices can be useful to confirm that a product can modulate skin reflectance without modifying constitutive pigmentation. The formula tested in this study did not interfere with constitutive melanogenesis.

A mechanistic view on the aging human skin through ex vivo layer-by-layer analysis of mechanics and microstructure of facial and mammary dermis.

Age-related changes in skin mechanics have a major impact on the aesthetic perception of skin. The link between skin microstructure and mechanics is crucial for therapeutic and cosmetic applications as it bridges the micro- and the macro-scale. While our perception is governed by visual and tactile changes at the macroscopic scale, it is the microscopic scale (molecular assemblies, cells) that is targeted by topical treatments including active compounds and energies. We report here a large dataset on freshly excised human skin, and in particular facial skin highly relevant for cosmetics and aesthetic procedures. Detailed layer-by-layer mechanical analysis revealed significant age-dependent decrease in stiffness and elastic recoil of full-thickness skin from two different anatomical areas. In mammary skin, we found that the onset of mechanical degradation was earlier in the superficial papillary layer than in the deeper, reticular dermis. These mechanical data are linked with microstructural alterations observed in the collagen and elastic networks using staining and advanced imaging approaches. Our data suggest that with ageing, the earliest microstructural and mechanical changes occur in the top-most layers of dermis/skin and then propagate deeper, providing an opportunity for preventive topical treatments acting at the level of papillary dermis.

Sunscreens with the New MCE Filter Cover the Whole UV Spectrum: Improved UVA1 Photoprotection In Vitro and in a Randomized Controlled Trial.

BACKGROUND: UVA1 rays (340-400 nm) contribute to carcinogenesis, immunosuppression, hyperpigmentation, and aging. Current sunscreen formulas lack sufficient absorption in the 370-400 nm wavelengths range. Recently, a new UVA1 filter, Methoxypropylamino Cyclohexenylidene Ethoxyethylcyanoacetate (MCE) exhibiting a peak of absorption at 385 nm, was approved by the Scientific Committee on Consumer Safety for use in sunscreen products. These studies evaluated, in a three-dimensional skin model and in vivo, the protection afforded by state-of-the-art sunscreen formulations enriched with MCE. TRIAL DESIGN: This study is a monocentric, double-blinded, randomized, and comparative trial. This study is registered at ClinicalTrials.gov with the identification number NCT04865094. METHODS: The efficacy of sunscreens with MCE was compared with that of reference formulas. In a three-dimensional skin model, histology, protein, and gene expression were analyzed. In the clinical trial, pigmentation was analyzed in 19 volunteers using colorimetric measurements and visual scoring. RESULTS: MCE addition in reference formulas enlarged the profile of absorption up to 400 nm; reduced UVA1-induced dermal and epidermal alterations at cellular, biochemical, and molecular levels; and decreased UVA1-induced pigmentation. CONCLUSIONS: Addition of MCE absorber in sunscreen formulations leads to full coverage of UV spectrum and improved UVA1 photoprotection. The data support benefits in the long term on sun-induced consequences, especially those related to public health care issues.

In vivo multiphoton multiparametric 3D quantification of human skin aging on forearm and face.

Quantifying skin aging changes and characterizing its 3D structure and function in a non-invasive way is still a challenging area of research, constantly evolving with the development of imaging methods and image analysis tools. In vivo multiphoton imaging offers means to assess skin constituents in 3D, however prior skin aging studies mostly focused on 2D analyses of dermal fibers through their signals' intensities or densities. In this work, we designed and implemented multiphoton multiparametric 3D quantification tools for in vivo human skin pigmentation and aging characterization. We first demonstrated that despite the limited field of view of the technic, investigation of 2 regions of interest (ROIs) per zone per volunteer is a good compromise in assessing 3D skin constituents in both epidermis and superficial dermis. We then characterized skin aging on different UV exposed areas-ventral and dorsal forearms, face. The three major facts of aging that are epidermal atrophy, the dermal-epidermal junction (DEJ) flattening and dermal elastosis can be non-invasively quantified and compared. Epidermal morphological changes occur late and were only objectified between extreme age groups. Melanin accumulation in suprabasal layers with age and chronic exposure on ventral and dorsal forearms is less known and appears earlier. Superficial dermal aging changes are mainly elastin density increase, with no obvious change in collagen density, reflected by SHGto2PEF ratio and SAAID index decrease and ImbrN index increase on all skin areas. Analysis of the z-dermal distribution of these parameters highlighted the 2nd 20 µm thickness normalized dermal sub-layer, that follows the DEJ shape, as exhibiting the highest aging differences. Moreover, the 3D ImbrN index allows refining the share of photoaging in global aging on face and the 3D SAAID index on forearm, which elastin or fibrillar collagens densities alone do not allow. Photoaging of the temple area evolves as a function of chronic exposure with a more pronounced increase in elastin density, also structurally modified from thin and straight elastic fibers in young volunteers to dense and compact pattern in older ones. More generally, multiphoton multiparametric 3D skin quantification offers rich spatial information of interest in assessing normal human skin condition and its pathological, external environment or product induced changes.

Actinic lentigines from Japanese and European volunteers share similar impaired biological functions.

BACKGROUND: Hyperpigmented spots develop earlier and with a higher incidence in Asian individuals compared with Europeans. Although actinic lentigines (AL) are very common, the biological events underlying their formation remain ill-defined. OBJECTIVE: AL from Japanese volunteers were characterized through morphological and gene expression analyses. Data were then compared with published data on European volunteers. METHODS: AL on hands were selected through dermoscopic imaging and pattern scoring in Japanese women. Skin biopsies of AL and adjacent non-lesional (NL) skin were processed for histology and gene expression profiling. Japanese and European studies were compared after harmonizing the data using the same mathematical and statistical methods. RESULTS: Histologically, AL from Japanese individuals revealed deep epidermal invaginations with melanin accumulation in the depth of epidermal rete ridges. Transcriptomic data identified 245 genes differentially expressed in AL versus NL skin samples, associated with the different skin compartments and multiple functional families and biological processes, such as epidermal homeostasis, extracellular matrix organization and ion binding/transmembrane transport. Strikingly, melanogenesis-related genes were not significantly modulated in AL compared with NL skin. Comparison of the molecular profiles of Japanese and European AL showed that a huge majority of genes were modulated in the same way, recapitulating the overall biological alterations. CONCLUSION: AL from Japanese volunteers exhibited morphological and molecular alterations of the whole skin structure with impairment of multiple biological functions similar to that found in European women. These findings will contribute to the development of efficient treatments of AL lesions.

A broad-spectrum sunscreen prevents UVA radiation-induced gene expression in reconstructed skin in vitro and in human skin in vivo.

The efficacy of sunscreens to protect against ultraviolet (UV) A radiation is usually assessed by measuring erythema formation and pigmentation. The biological relevance of these endpoints for UVA-induced skin damage, however, is not known. We therefore carried out two complementary studies to determine UVA protection provided by a broad-spectrum sunscreen product at a molecular level by studying UVA radiation-induced gene expression. One study was performed on human reconstructed skin in vitro with a semi-global gene expression analysis of 227 genes in fibroblasts and 244 in keratinocytes. The second one was conducted in vivo in human volunteers and focused on genes involved in oxidative stress response and photo-ageing (haeme oxygenase-1, superoxide dismutase-2, glutathione peroxidase, catalase, matrix metalloproteinase-1). In-vitro UVA radiation induced modulation of genes involved in extracellular matrix homeostasis, oxidative stress, heat shock responses, cell growth, inflammation and epidermal differentiation. Sunscreen pre-application abrogated or significantly reduced these effects, as underlined by unsupervised clustering analysis. The in vivo study confirmed that the sunscreen prevented UVA radiation-induced transcriptional expression of the five studied genes. These findings indicate the high efficacy of a broad-spectrum sunscreen in protecting human skin against UVA-induced gene responses and suggest that this approach is a biologically relevant complement to existing methods.

UVA Exposure Combined with Glycation of the Dermis Are Two Catalysts for Skin Aging and Promotes a Favorable Environment to the Appearance of Elastosis.

Skin aging is the result of superimposed intrinsic (individual) and extrinsic (e.g., UV exposure or nutrition) aging. Previous works have reported a relationship between UV irradiation and glycation in the aging process, leading, for example, to modified radical species production and the appearance of AGEs (advanced glycosylation end products) in increasing quantities, particularly glycoxidation products like pentosidine. In addition, the colocalization of AGEs and elastosis has also been observed. We first investigated the combination of the glycation reaction and UVA effects on a reconstructed skin model to explain their cumulative biological effect. We found that UVA exposure combined with glycation had the ability to intensify the response for specific markers: for example, MMP1 or MMP3 mRNA, proteases involved in extracellular matrix degradation, or proinflammatory cytokine, IL1α, protein expression. Moreover, the association of glycation and UVA irradiation is believed to promote an environment that favors the onset of an elastotic-like phenomenon: mRNA coding for elastin, elastase, and tropoelastin expression is increased. Secondly, because the damaging effects of UV radiation in vivo might be more detrimental in aged skin than in young skin due to increased accumulation of pentosidine and the exacerbation of alterations related to chronological aging, we studied the biological effect of soluble pentosidine in fibroblasts grown in monolayers. We found that pentosidine induced upregulation of CXCL2, IL8, and MMP12 mRNA expression (inflammatory and elastotic markers, respectively). Tropoelastin protein expression (elastin precursor) was also increased. In conclusion, fibroblasts in monolayers cultured with soluble pentosidine and tridimensional in vitro skin constructs exposed to the combination of AGEs and UVA promote an inflammatory state and an alteration of the dermal compartment in relation to an elastosis-like environment.

Multi-omics analysis to decipher the molecular link between chronic exposure to pollution and human skin dysfunction.

Environmental pollution is composed of several factors, namely particulate matter (PM2.5, PM10), ozone and Ultra Violet (UV) rays among others and first and the most exposed tissue to these substances is the skin epidermis. It has been established that several skin disorders such as eczema, acne, lentigines and wrinkles are aggravated by exposure to atmospheric pollution. While pollutants can interact with skin surface, contamination of deep skin by ultrafine particles or Polycyclic aromatic hydrocarbons (PAH) might be explained by their presence in blood and hair cortex. Molecular mechanisms leading to skin dysfunction due to pollution exposure have been poorly explored in humans. In addition to various host skin components, cutaneous microbiome is another target of these environment aggressors and can actively contribute to visible clinical manifestation such as wrinkles and aging. The present study aimed to investigate the association between pollution exposure, skin microbiota, metabolites and skin clinical signs in women from two cities with different pollution levels. Untargeted metabolomics and targeted proteins were analyzed from D-Squame samples from healthy women (n = 67 per city), aged 25-45 years and living for at least 15 years in the Chinese cities of Baoding (used as a model of polluted area) and Dalian (control area with lower level of pollution). Additional samples by swabs were collected from the cheeks from the same population and microbiome was analysed using bacterial 16S rRNA as well as fungal ITS1 amplicon sequencing and metagenomics analysis. The level of exposure to pollution was assessed individually by the analysis of polycyclic aromatic hydrocarbons (PAH) and their metabolites in hair samples collected from each participant. All the participants of the study were assessed for the skin clinical parameters (acne, wrinkles, pigmented spots etc.). Women from the two cities (polluted and less polluted) showed distinct metabolic profiles and alterations in skin microbiome. Profiling data from 350 identified metabolites, 143 microbes and 39 PAH served to characterize biochemical events that correlate with pollution exposure. Finally, using multiblock data analysis methods, we obtained a potential molecular map consisting of multi-omics signatures that correlated with the presence of skin pigmentation dysfunction in individuals living in a polluted environment. Overall, these signatures point towards macromolecular alterations by pollution that could manifest as clinical sign of early skin pigmentation and/or other imperfections.

Bifidobacterium longum lysate, a new ingredient for reactive skin.

Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non-replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF-alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3-1%), the probiotic lysate significantly inhibited capsaicin-induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double-blind, placebo-controlled trial. Sixty-six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans-epidermal water loss following barrier disruption induced by repeated tape-stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self-assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin.

Lactobacillus paracasei CNCM I-2116 (ST11) inhibits substance P-induced skin inflammation and accelerates skin barrier function recovery in vitro.

Over the past few decades the number of people presenting reactive skin has increased in industrial countries. Skin inflammation mediated by neuropeptides and impaired skin barrier function are both underlying features of reactive skin conditions. Live microorganisms defined as probiotics have been successfully used to improve health status in humans. Beyond the effects on intestinal microbiota, some probiotic strains display potent immune-modulatory properties at the skin level. The aim of this study was to evaluate whether Lactobacillus paracasei CNCM-I 2116 (ST11) could modulate reactive skin-associated inflammatory mechanisms. The Caco-2/PBMC co-culture cell system was stimulated on the apical side with probiotics. The resulting medium collected from the basolateral compartment of the cell culture system, so called conditioned medium, was tested in ex vivo human abdominal plastic skin explant models of substance P-induced skin inflammation and skin barrier reconstruction. We show that ST11 was able to abrogate vasodilation, edema, mast cell degranulation and TNF-alpha release induced by substance P, compared to control. Moreover, using ex vivo skin organ culture, we show that ST11-conditioned medium induced a significantly faster barrier function recovery after SLS disruption, compared to control. These results support a beneficial role of ST11 on key biological processes associated with barrier function and skin reactivity.

Human exposure to PCBs, PBDEs and bisphenols revealed by hair analysis: A comparison between two adult female populations in China and France.

Humans are exposed to various anthropogenic chemicals in daily life, including endocrine-disrupting chemicals (EDCs). However, there are limited data on chronic, low-level exposure to such contaminants among the general population. Here hair analysis was used to investigate the occurrence of four polychlorinated biphenyls (PCBs), seven polybrominated diphenyl ethers (PBDEs) and two bisphenols (BPs) in 204 Chinese women living in the urban areas of Baoding and Dalian and 311 pregnant French women. All the PCBs and PBDEs tested here were more frequently detected in the hair samples of the French women than in those of the Chinese women. In both cohorts, PCB 180 and BDE 47 were the dominant PCB and PBDE congener, respectively. PCB 180 was found in 82% of the French women and 44% of the Chinese women, while the corresponding values of BDE 47 were 54% and 11%, respectively. A discriminant analysis further demonstrated the difference in PCBs and PBDEs exposure profile between the two cohorts. These results demonstrate that hair analysis is sufficiently sensitive to detect exposure to these pollutants and highlight differences in exposure between populations even at environmental levels. Although BPA and BPS were found in 100% of the hair samples in both cohorts, the French women had significantly higher levels of BPA and BPS than the Chinese women. The median concentrations of BPA were one order of magnitude higher than BPS in both the Chinese (34.9 versus 2.84 pg/mg) and the French women (118 versus 8.01 pg/mg) respectively. Our results suggest that both French and Chinese populations were extensively exposed to BPA and BPS.

Exposure to multiclass pesticides among female adult population in two Chinese cities revealed by hair analysis.

The high use of pesticides worldwide and the constant exposure of humans to these toxic-by-design chemicals have drawn the attention on the possible consequences on human health. However, information on the exposure of the general population to pesticides remain very limited in most countries, especially in urban areas. In the present work, hair analysis was conducted to investigate the exposure of 204 urban women living in two Chinese cities (Baoding and Dalian) to 110 pesticides and 30 metabolites of the following families: organochlorines, organophosphates, carbamates, pyrethroids, neonicotinoids, phenylpyrazoles, acid herbicides, urea herbicides and azoles. Results showed that 71 pesticides and 23 metabolites were found in the hair samples, with concentrations ranging up to 1070 pg/mg in hair. In each hair sample, the number of detected chemicals ranged from 25 to 50, demonstrating the cumulative exposure to pesticides among Chinese women in the studied regions. The concentrations of 38 chemicals (e.g., p-nitrophenol, diethyldithiophosphate, λ-cyhalothrin, permethrin, carbendazim and tebuconazole) were significantly different between women in Baoding and Dalian, indicating the regional differences in exposure to pesticide. Using a multiple regression analysis, we found that concentrations of a few dominant pesticides were associated with age, body mass index (BMI), cooking frequency and regions. These results can provide baseline information on exposure of female adult Chinese population to multiple pesticides and support future studies focused on the health effects associated with pesticide exposure.

Changes of the human skin microbiota upon chronic exposure to polycyclic aromatic hydrocarbon pollutants.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are of environmental and public health concerns and contribute to adverse skin attributes such as premature skin aging and pigmentary disorder. However, little information is available on the potential roles of chronic urban PAH pollutant exposure on the cutaneous microbiota. Given the roles of the skin microbiota have on healthy and undesirable skin phenotypes and the relationships between PAHs and skin properties, we hypothesize that exposure of PAHs may be associated with changes in the cutaneous microbiota. In this study, the skin microbiota of over two hundred Chinese individuals from two cities in China with varying exposure levels of PAHs were characterized by bacterial and fungal amplicon and shotgun metagenomics sequencing. RESULTS: Skin site and city were strong parameters in changing microbial communities and their assembly processes. Reductions of bacterial-fungal microbial network structural integrity and stability were associated with skin conditions (acne and dandruff). Multivariate analysis revealed associations between abundances of Propionibacterium and Malassezia with host properties and pollutant exposure levels. Shannon diversity increase was correlated to exposure levels of PAHs in a dose-dependent manner. Shotgun metagenomics analysis of samples (n = 32) from individuals of the lowest and highest exposure levels of PAHs further highlighted associations between the PAHs quantified and decrease in abundances of skin commensals and increase in oral bacteria. Functional analysis identified associations between levels of PAHs and abundance of microbial genes of metabolic and other pathways with potential importance in host-microbe interactions as well as degradation of aromatic compounds. CONCLUSIONS: The results in this study demonstrated the changes in composition and functional capacities of the cutaneous microbiota associated with chronic exposure levels of PAHs. Findings from this study will aid the development of strategies to harness the microbiota in protecting the skin against pollutants. Video Abstract.