Vichy Exposome Grant

Scalp health has lately attracted the public attention, because of its contribution to optimal hair growth, which is crucial to our physical appearance and self-perception. As the first line of physical defense against stressors, scalp and hair are affected by multiple exposome factors. Both internal factors such as aging and hormone and external factors like UV radiation (UVR) may influence scalp health.

Dandruff and seborrheic dermatitis (D/SD) are a common scalp condition frequently seen in clinical practice and have a huge impact on our quality of life. The exact pathophysiology of D/SD is poorly understood. Besides Malassezia spp. and its interaction with skin immune system, environmental factors including UVR, and low vitamin D levels might also be involved in D/SD. It is reported that scalp and hair in D/SD patients exhibit clear signs of oxidative stress.

Currently the systematic effects of exposome on scalp health in Asian populations remain unknown. To fill the gap, we aim to investigate the scalp condition of the Chinese female population. Using D/SD as a model, we will study the combined effect of external (UVR) and internal exposure factors (hormone, age, vitamin D) on scalp health. These findings will help better understand the impact of exposome on scalp health, particularly for the population in China.

Host defense (antimicrobial) peptides (HDPs) constitute a crucial part of the epidermal innate immunity and function as the foremost barrier against external environmental threats. Human β-defensins (hBDs), one of the major families of HDPs found in mammals, are multi-functional cationic peptides expressed by various cell types including cells in the skin epithelia. Although hBDs are known to exhibit many immunomodulatory functions, the photo-protective effects of hBDs have never been explored before in the literature. Therefore, we aim to investigate the potential roles of hBDs on human dermal fibroblasts in UVB-induced photoaging. Discovering novel functions of hBDs will not only implement the basic knowledge in immunodermatology, but also enlighten physicians to develop promising treatment strategies for patients with photodermatoses.

Exposome factors can damage the skin by altering skin homeostasis and epidermal barrier (EB) function.

Sun exposure, air pollution, cigarette smoke, hormone exposure, the diet and sleep disturbances are exposome factor that may impair EB. Assessment of the EB usually involves measurements of Transepidermal Water Loss (TEWL). Stratum corneum hydration (SCH), skin surface pH, temperature, elasticity, melanin, erythema, skin gloss, stiffness and deformability are other factors to assess EB function. We previously found that age, sun and tobacco were associated with skin ageing and that a skin care routine delayed skin ageing.

Moreover, we observed that UVB changes skin homeostasis and EB function in psoriatic patients. Recently, it has been described that human tissue engineering skin substitute (hTESS) are exemplary models for evaluating the impact of extrinsic factors on the skin. We have manufactured a new hTESS with fibrin-hyaluronic acid (HA) biomaterial suitable for wound healing and we have tested the impact of different chemical products on hTESS. It is important to evaluate the impact of exposome factors both in vitro and in vivo. Knowing how each factor damage the skin and what are the most harmful, would help researchers to develop products that decrease EB impairment.

The aim of this project is to investigate skin homeostasis alterations and EB disruption induced by exposome factors both in vitro using hTESSs and in vivo evaluating healthy volunteers.

Plastic-based products are ubiquitous due to their tremendous utility in our daily lives. However, the limited biodegradable nature of plastics, especially micro- and nanoplastics (MPs/NPs), has recently raised global pollution concerns. These anthropogenic pollutants, currently widespread in the oceans, freshwater bodies, land or even present in food, are either manufactured specifically in the small size range for various commercial applications or formed due to fragmentation of macroplastics in the environment.

The biological effects of MPs and NPs on aquatic organisms are well documented but their impacts on the mammalian system have not been deeply investigated and data on the impact on the human body at subcellular or molecular levels is scarce. In particular, the penetration of these particles through the skin epithelia and their effect on skin health has not been examined thoroughly.

Therefore, going behind the state of the art, this project aims to elucidate the potential pathological events triggered by different MPs/NPs on skin with focus on oxidative and inflammatory damages, as well as aging-related events, at different levels of biological complexity (molecular, cellular and organ levels).

Ultimately, this proposal will allow to identify the adverse outcome pathway (AOP) triggered by MPs/NPs exposome at the skin level.

Melasma is a chronic skin disorder that mainly affects women during fertile age, and its pathogenesis is still not fully understood. Sun exposure is the major risk factor for melasma development. It induces a skin stress response that causes premature cellular senescence and can activate Aryl Hydrocarbon Receptor (AhR). When AhR is activated, it promotes upregulation of tyrosinase. AhR is an exposome receptor, because it is activated by a variety of ligands, including xenobiotics (as dioxins and other polycyclic aromatic hydrocarbons), natural products, microbiome metabolites, and endogenous molecules.

A significant increase in the incidence of melasma is well documented in the past decade, especially in urban areas where air pollution also increased. Air pollution plays an important role in extrinsic aging and pigmentation. Until now, AhR expression has never been evaluated in melanocytes and keratinocytes from melasma skin. This study aims to evaluate the expression of AhR in keratinocytes, basal layer melanocytes, and pendulum melanocytes from the facial melasma skin of women compared to the expression in adjacent healthy skin.

Twenty women will be biopsied in two different areas: melasma and healthy adjacent skin. Fragments will be submitted to triple-labeled immunofluorescence: anti-AhR, anti-vimentin and DAPI. The slides will be photographed at a confocal microscopy equipment and semiquantitative blind analysis will be performed on suprabasal keratinocytes, basal layer melanocytes and pendulum melanocytes (nucleus and cytoplasm).

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that mainly affects the urban population and is characterized by pruritic eczematous lesions. Since the disease is associated with dysbiosis, selective modulation of the microbiota of each patient has become a topic of great interest. In this context, knowing the relationship between exposome atmospheric pollution and the microbiota of atopic patients is part of the process for a better selective modulation of microorganisms found in the skin. Given the above, this project aims to evaluate the skin microbiota of patients, children, and adults, diagnosed with AD in two different cities, one with high and the other with low level of pollution.

Skin aging is an important health issue and public concern. In the real world, the body’s skin is exposed to the mixture of different air pollutants and climatic conditions (e.g., ambient heat) rather than a single environmental factor. Although the individual impact of these hazards on skin aging has been discussed, their interactive and combined effects remain largely unclear. As a result, the role of exposome on skin aging may have been underestimated. The lack of investigation is particularly true in China – a country is facing a heavy health burden from air pollution exposure, climate change, and population aging.

To fill the research gap, this project will explore the independent, interactive, and combined effects of chronic exposure to different air pollutants (i.e., particulate matter, nitrogen dioxide, and ozone) and ambient heat on skin aging in the Chinese elderly. The project will make use of the Taizhou study cohort. Located at the junction of north and south China, Taizhou is in the middle of the spectrum – both geographically, climatically, and genetically, which promises the representativeness of our results. The findings will help to understand the impact of environmental factors as a whole on skin aging in Chinese elderly.

Research on skin health involve interdisciplinary subjects. On the one hand, the individual's behavior, lifestyle and genetic factors. On the other hand, external factors such as exposure to the sun, weather and air pollution. The lack of studies that integrate these intrinsic and extrinsic factors limit the advance of knowledge about skin health. This lack is due to several factors, such as:
a) difficulties in integrating interdisciplinary research;
b) the limited use of recent data analysis tools (data mining, big data, machine learning, etc.);
c) the high cost of collecting, storing and transmitting data provided by obsolete systems; and, specifically related to the extrinsic aspects,
d) the lack of consistent meteorological measurement networks, mainly in less developed countries.

This research project aims to integrate low-cost environmental measurements, data transmission systems and data analysis to provide scientific and educational information for the industry, scientists and society. For this purpose, we propose an experimental set of environmental measurements based on a new generation of low-cost instruments and wireless data transmission performed in different Brazilian regions. In parallel, studies on photoprotection behavior and skin damage can be conducted in these areas. These data will feed a database for deep analysis based on statistical tools. This research project will be conducted by a multidisciplinary team involving physicists, doctors, chemists and engineers. We hope that this interdisciplinary effort can bring relevant contributions for the understanding of skin exposome.