External Exposome Influences on the Skin and Its Barrier

The exposome defines and encompasses all environmental exposures an individual encounters throughout their lifetime and the ways these exposures influence biological functions and health outcomes. It comprises both external and internal factors—such as chemical, physical, biological and social influences—that may affect health. The skin’s exposome specifically pertains to the total environmental exposures that can lead to or modify skin conditions. Environmental factors such as ultraviolet (UV) exposures, pollution, diet, stress and smoking adversely affect the skin by inducing oxidative stress, degrading collagen and elastin, weakening the skin barrier and promoting inflammation. This leads to premature signs of aging, including wrinkles and hyperpigmentation, as well as dryness, dullness, sensitivity, redness and exacerbation of skin conditions such as acne, eczema and hyperpigmentation. It is essential to recognize that these factors often interact synergistically—for example, pollution exposure is exacerbated by UV radiation, which accelerates skin damage beyond the impact of any individual factor. (1.,2.)

Revisiting Barrier Basics

The skin constitutes the body’s largest organ, serving as a vital safeguard between internal organs and the external environment. From a structural standpoint, the epidermis serves as a resilient physical barrier that prevents the ingress of microorganisms and potential toxins while preserving moisture and essential nutrients within its layers. The epidermis is an active system characterized by continuous proliferation and differentiation and comprises keratinocytes, melanocytes and immunocompetent cells. The intricate composition of the stratum corneum is vital to the skin's barrier function, with corneocytes embedded within a matrix of multiple lamellar lipid layers. The skin also displays distinctive physical and chemical properties, thereby creating an environment conducive to specific microorganisms. 

The interaction among the skin microbiome, lipids and the skin barrier function is notably complex, with each element contributing significantly to the maintenance of cutaneous health and the prevention of disease. 

The commonly cited “skin barrier” primarily refers to the stratum corneum (SC), which preserves skin integrity. Essential constituents of the SC include corneocytes, intercellular lipid lamellae, corneodesmosomes and tight junctions. The integrity of the skin barrier relies on three principal components: lipids within the stratum corneum (SC), natural moisturizing factors (NMFs) and the acidic pH of the SC surface. The maintenance of skin acidity is achieved through three internal mechanisms: free fatty acids derived from phospholipids; trans-urocanic acid produced from filaggrin (FLG) and the sodium-hydrogen exchanger (NHE), a membrane protein that employs the sodium gradient to facilitate ion transport and support essential cellular functions, such as the regulation of intracellular ph. 

The stratum corneum (SC) maintains an acidic pH, which is crucial for preserving a healthy skin barrier. An acidic environment within the SC enhances the activity of enzymes essential for ceramide synthesis, thereby promoting skin health. Conversely, an elevated pH may heighten the risk of skin infections, reduce the activity of lipid-processing enzymes, hinder the repair of the permeability barrier and compromise the structural integrity and cohesion of the SC. Additionally, this acidic environment fosters the proliferation of beneficial microorganisms while inhibiting pathogenic ones. Such a biological equilibrium reinforces the integrity of the skin barrier by modulating enzymes responsible for degrading SC proteins and supports skin hydration through the regulation of enzymes involved in NMF synthesis. Natural moisturizing factors (NMFs) are inherent components of the skin and are crucial in sustaining hydration. These elements comprise amino acids, lactate and urea, among others. NMFs facilitate the attraction of water molecules to the skin's surface and interact with lipids to establish a barrier that mitigates trans epidermal water loss (TEWL). A deficiency in NMF levels may result in skin dehydration, dryness and potential impairment of the barrier function. 

There has been a growing focus on protecting the skin's surface with products labeled as "barrier repair” solutions. However, emphasis should not be placed on a 'barrier repair' product as the sole resolution for a compromised skin.

Underlying skin issues may have broad implications for the barrier, potentially involving subclinical factors that may justify dermatological or medical intervention. It is also crucial to evaluate complete ingredient decks and skin compatibility, as well as the type and frequency of esthetic procedures performed, with skin homeostasis as the primary objective. The stability of the physiological barrier depends on the complex interplay among epidermal functions, microbiome interactions and the supply of essential lipids. Crucially, supporting overall skin health begins with a thorough assessment of the client’s skin and their 'exposome,' which encompasses exposures, lifestyle, medications and their history of product and aesthetic services use. (3,4.)

Skin Barrier Super Stars

Corneocytes 

Corneocytes are keratinocytes that have completed their final differentiation stage. They retain keratin filaments within a filaggrin matrix, and a cornified lipid envelope replaces their plasma membrane. These flat cells form the stratum corneum, which is organized in a brick-and-mortar pattern within a lipid-rich extracellular matrix. They are essential to the skin's physical defense, with keratin networks providing structure and flexibility. Embedded in a lipid-rich matrix, corneocytes help maintain barrier function and prevent water loss.

Intercellular Lipids (Lamellae)

As keratinocyte differentiation progresses, accumulated lipids are stored in specialized organelles called lamellar bodies (granules or Odland bodies). These lipids are released from the granules at the boundary between the topmost granular cells and the bottom of the stratum corneum, entering the intercellular space. During their passage into the stratum corneum, the lipids interact with hydrolytic enzymes, yielding a mixture of ceramides, cholesterol and fatty acids that fill the intercellular spaces. These intercellular lipids form the skin’s essential permeability barrier. The lipids present in the stratum corneum include ceramides, cholesterol and free fatty acids. Their primary function is to prevent trans-epidermal water loss (TEWL) by establishing a barrier that retains moisture. When this lipid barrier is compromised—due to external factors such as harsh soaps or internal causes such as genetics—TEWL increases, potentially resulting in dry and irritated skin.

Corneodesmosomes

The thickness of the stratum corneum remains relatively constant due to a balance between new cell production and the removal of old cells. Corneodesmosomes function as the primary intercellular adhesive structures within this layer. They originate from desmosomes situated in the most superficial region of the stratum granulosum of the epidermis. A significant distinction from desmosomes is the presence of corneodesmosin in their extracellular domains. Upon the complete degradation of these extracellular components, desquamation occurs. 

Tight Junctions

Tight junctions (TJs) are vital multiprotein complexes located within the epidermis. They serve as a "gate" that seals the intercellular spaces between keratinocytes, regulating the translocation of water, ions and solutes. Consequently, they constitute a critical element of the skin's barrier system alongside the stratum corneum. Tight junctions oversee the paracellular pathway between cells and are indispensable for maintaining homeostasis. They are integral to epithelial and endothelial tissues by sealing intercellular spaces to establish selective barriers. These barriers govern the movement of substances between body compartments, prevent the leakage of fluids, ions and microorganisms, and help maintain cell polarity.

Aquaporins

Another essential element of skin hydration is the presence of aquaporins, which are proteins responsible for facilitating water transport within the skin. These channels assist in regulating water movement and maintaining osmotic equilibrium, particularly in dry environments. Although they are not as extensively discussed as lipids or filaggrin, aquaporins are increasingly recognized in dermatological research for their potential to enhance moisture retention. 

Filaggrin

A key barrier element is the multifunctional epidermal protein filaggrin (FLG). FLG originates from a large precursor called pro-filaggrin, which is contained within the stratum granulosum keratinocytes. As keratinocytes undergo cornification, pro-filaggrin is enzymatically processed into deiminated filaggrin molecules. These molecules are dispersed within corneocytes and partially cross-link to the cornified envelopes. Ultimately, free amino acids produced from filaggrin breakdown constitute the primary component of the natural moisturizing factor (NMF) in the stratum corneum (SC). They exhibit an excellent ability to retain water and help maintain the SC's low pH.

Sebum

The primary lipids present on the skin's surface are essential for maintaining skin health and functionality. The skin’s stratum corneum constitutes a lipid- and protein-rich, cornified outer layer that encompasses hair follicles and sebaceous glands. These structures supply vital lipids, antimicrobial peptides, enzymes, salts and other compounds. Its acidity and high oxygen content characterize the environment, and it features a distinctive and complex mixture of lipids not found elsewhere in the human body. Features such as the acidic pH and barrier function not only affect the skin’s appearance but also its overall barrier integrity and microbial homeostasis. Sebum possesses natural antibacterial properties and can exert both pro- and anti-inflammatory effects by regulating harmful substances and xenobiotics.

Microbiome

Microbiota are not confined to the skin surface; they also reside within hair follicles, sebaceous glands, sweat glands and even the dermis. The presence of bacteria in the dermis supports evidence that cells beneath the outer skin layer respond to commensal microbial products. The skin’s microbiome, composed of billions of microorganisms, interacts intricately with epidermal lipids that form the outer barrier, playing a crucial role in maintaining skin integrity and function. The skin serves as a primary site of microbial-host interactions. It features a complex landscape rich in lipids and proteins, along with follicles and glands that establish distinct physical and chemical environments. Bacterial colonization on human skin is vital for defense mechanisms and support of both innate and adaptive immune responses. The composition of the microbiome is meticulously regulated by factors such as epidermal pH and the skin's immune system. Consequently, the efficacy of the epidermal barrier depends on the interconnected communication among the chemical barrier, the immune system and the microbiota. Furthermore, the skin microbiome transmits environmental signals, including xenobiotics, to the skin’s immune network. (5.,6.,7.,8.)

The External Exposome and Trans Barrier Influences

Eco-biological principles view the skin as a dynamic ecosystem that interacts continuously with its environment, underscoring the need to protect its natural resources and functions. These principles examine how cells communicate and interact both internally and externally. As the skin is the primary interface with the environment, it depends on ecosystem biodiversity, lifestyle choices, host factors and environmental conditions to sustain its balance. The decline in global biodiversity and shrinking natural habitats can reduce microbial diversity, potentially disrupting the relationship between the skin barrier and microbial communities. This loss affects microbial habitats and may lead to dysbiosis, thereby increasing the risk of inflammatory skin conditions. Barrier abnormalities and pathogen colonization can also occur in many other inflammatory skin diseases, including seborrheic dermatitis, stasis dermatitis and rosacea, as well as more serious skin bacterial infections:

• Carbuncles
• Cellulitis
• Ecthyma
• Erysipelas
• Erythrasma
• Folliculitis
• Furuncles
• Impetigo
• Lymphadenitis
• Lymphangitis
• Necrotizing skin infections
• Staphylococcal scalded skin syndrome

Bacteria multiply in specific opportunistic circumstances:

• Barrier dysfunction compromised skin
• Climate and temperature changes
• Compromised immunity.
• Decline of microbiota
• Extreme PH disturbances
• Injuries, surgery
• Medications – topical and systemic
• Pathogen infiltrates
• Poor Hygiene 

Skin Bacteria:

• Acinetobacteria species (small numbers)
• Alpha -hemolytic and nonhemolytic Streptococcus
• Brevibacterium
• Corynebacterium
• Corynebacterium minutissmim
• Cutibacterium acne (formerly Propionibacterium acnes) porphyrins
• Dermabacterium
• Diptheroid
• Folliculitis Impetigo
• Methicillin-resistant Staphylococcus aureus (MRSA) – Antibiotic resistant – may be community acquired or (CA-MRSA) or hospital acquired HA-MRSA)
• Micrococcus species
• Neisseriae species (nonpathogenic)
• Peptoststreptococcus species
• Proteobacteria - Escherichia, Salmonella, Vibrio, Helicobacter, Yersinia, Legionellae
• Pseudomonas aeruginosa (hospitals)
• Staphylococcus aureus
• Staphylococcus epidermidis
• Staphylococcus warneri
• Streptococcus 

(9.,10.)

The physiological impact on barrier function.Image courtesy of Dr. Erin Madigan-Fleck.

Environmental factors induce changes in the skin that may attract immune cells, which mediate local and systemic responses to maintain homeostasis. The skin and its barrier are often exposed to a range of air pollutants, and their effects vary with pollutant characteristics and the intensity and duration of exposure. Moreover, the mechanisms responsible for skin damage vary with the skin’s interactions with pollutants or co-pollutants. Generally, air pollution induces an oxidative stress response in the skin, triggering inflammation that contributes to both dermatological and systemic pathologies. Prolonged UVR exposure can intensify these health effects through harmful synergistic impacts. Additionally, air pollution may trigger or worsen various skin and systemic conditions, including premature skin aging, skin cancers (such as melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), inflammatory skin disorders (like atopic dermatitis (AD), airborne contact dermatitis (ABCD), allergic contact dermatitis and psoriasis), as well as acne, alopecia and pigmentary issues such as vitiligo, melasma, post-inflammatory pigment changes and various neurodermatoses.

Ultraviolet radiation (UVR) is the most harmful environmental factor affecting skin health, causing photodamage in sun-exposed areas over time. This damage accelerates skin aging and raises the risk of skin cancer. Solar UVR reaching Earth primarily comprises UVB (290–320 nm) and UVA (320–400 nm), which affect the skin and other tissues differently. UVB damages tissues primarily by absorbing chromophores, such as DNA and proteins, thereby inducing mutations and generating reactive oxygen species (ROS). UVA mainly causes damage by generating ROS and reactive nitrogen species (RNS), with less absorption by cellular chromophores. 

Controversy surrounds the harmful effects of blue light from the most energetic part of the visible spectrum on skin, its barrier and circadian rhythms. With the widespread use of electronic devices, light pollution is increasingly concerning for human health. 

Exposure to blue light from screens (456 nm) and LEDs during day and night is under growing scrutiny. Unlike UV rays, blue light penetrates deeper into the subcutaneous tissue, and there is strong evidence linking it to retinal damage and degeneration, primarily through the induction of ferroptosis—a form of cell death driven by iron-induced lipid peroxidation.

We encounter various chemicals and compounds daily, including radiation, airborne particles, vapors, gases and water pollutants often found in personal care products. Many industrial, household and personal items emit chemical vapors or contain substances such as synthetic chemicals, phthalates, formaldehyde, PVC, BBA, BPS, VOCs, nitrate radicals, acetaldehyde, benzene, polybrominated diphenyl ethers (PBDEs), chloroform, triclosan, D-limonene, terpenoids, xylene, ethylene glycol ethers and more. A single chemical agent can enter the human body through inhalation, ingestion or dermal contact. 

Detrimental chemical exposures also include nicotine, liquid cigarette and vaping compounds, which not only impact the user but also people and the environment around them. These exposures, particularly from lipophilic polyaromatic hydrocarbons, such as particulate matter (PM) and cigarette smoke, can disrupt cellular homeostasis by generating ROS/RNS, either independently or after UVA exposure. Their small size enables them to enter mitochondria, thereby promoting ROS production and mitochondrial damage. PMs also possess oxidative potential due to metals such as iron and copper, which catalyze reactions. Ozone can generate 4HNE by oxidizing fatty acids in the skin, thereby creating peroxides that deplete antioxidants such as vitamin C, glutathione, uric acid and vitamin E.

Smoking contributes to comedogenesis through its chemical constituents and toxic by-products, which cause vascular changes and oxidative stress. Nicotine induces vasoconstriction, reducing blood flow and promoting localized hypoxia, which in turn promotes the overgrowth of Cutibacterium acnes by disrupting the skin microbiome. It also increases ROS levels, oxidizing sebum lipids, such as squalene, to squalene monohydroperoxide—a compound associated with hyperkeratinization and comedone formation. 

This oxidative stress depletes the skin of antioxidants, including α-tocopherol (vitamin E). It impairs mitochondrial function in keratinocytes and sebocytes, thereby altering sebum composition and contributing to pore blockage. The resulting form of non-inflammatory acne, known as atypical post-adolescent acne (APAA) or "smoker’s acne," mainly appears as closed comedones and microcysts rather than pustules.

E-cigarette liquids (e-liquids) are heated in the skin and mouth, and vaporization produces toxic by-products that generate reactive oxygen species (ROS) and free radicals, leading to oxidative damage. When heated at high temperatures, the solvent carriers—propylene glycol and glycerol—release volatile organic compounds. In addition to volatile organic compounds, e-liquids contain heavy metals such as lead, nickel and chromium, which the FDA deems potentially harmful upon absorption.

Although e-cigarettes contain lower levels of heavy metals compared to tobacco cigarettes, the heating element significantly increases exposure to nickel. Nickel is a typical contact allergen and toxic, with its toxicity linked to oxidative stress. Carbonyl compounds like acrolein and formaldehyde can damage mitochondrial function and induce lipid peroxidation. Acrolein, a reactive carbonyl compound, impairs mitochondrial function, whereas formaldehyde, a carcinogen, increases oxidative stress by elevating ROS and other free radicals that can generate endogenous formaldehyde. These reactive molecules can trigger lipid peroxidation, leading to lipid peroxide formation that may alter skin inflammation and immune responses, suggesting a potential link between e-cigarette use and the development or worsening of skin conditions. Environmental pollution also encompasses a range of ground-level pollutants, including carbon monoxide (CO), lead (Pb), nitrogen dioxide (NO₂), ozone (O₃), particulate matter (PM) and sulfur dioxide (SO₂). Ozone in the environment is considered highly toxic and among the most harmful airborne pollutants to human health due to its high reactivity with biological membranes. Approximately 90% of ozone naturally resides in the stratosphere, where it filters UV radiation before it reaches the Earth's surface. 

Ground-level ozone forms as photochemical smog, produced by reactions involving sunlight, nitrogen oxides, and hydrocarbons emitted by vehicle exhaust. It is essential to distinguish this form of ozone from that used for medical treatments or aesthetic purposes, as the latter is produced via a corona discharge (electrical charge emitted by air, liquid, or gas). Damage to the skin caused by atmospheric ozone involves direct interaction with and oxidation of polyunsaturated fatty acids (PUFAs) and lipids in the stratum corneum (SC), leading to the formation of aldehydes and reactive oxygen species (ROS), such as H₂O₂. These reactive mediators can propagate ozone-induced toxicity, impair the skin barrier and exacerbate injury deeper within the skin layers.

The predominant route of chemical absorption is direct contact, primarily via diffusion. Passive diffusion entails the permeation of the chemical through the stratum corneum, entry into the epidermis and ultimately into the dermis, where it can be transported systemically via the dermal vasculature. Frequently, chemicals remain undetected during the absorption process because they gradually accumulate within tissues, and this accumulation may only become evident through clinical signs such as rash, edema, erythema, pigmentation changes, eczema or other dermatological indications. Chemicals with a low molecular weight (less than 500 Dalton), which are soluble in both aqueous and lipophilic environments, tend to penetrate the skin more rapidly and effectively than compounds that are predominantly lipophilic or hydrophilic. Nonetheless, evidence suggests that compromised skin integrity or barrier dysfunction—induced by physical or chemical damage—can enhance dermal absorption by disrupting the lipid and protein structure of the stratum corneum, thereby facilitating systemic absorption of chemicals. This process may also involve larger molecules, including proteins, metal compounds or hazardous nanoparticles.

The rate and extent of absorption of a chemical is subject to the following factors: 

• Integrity of the skin
• Barrier function
• Location of the exposure
• Water content of the stratum corneum
• Concentration of the chemical on the surface
• Duration of the exposure
• The degree of surface area exposed to the chemical

Dermal exposure to chemicals and solvents has been shown to reduce the skin's barrier function by altering lipid and protein structures of the stratum corneum, thereby promoting systemic uptake of the solvent itself or other chemicals. (11 to 19)

Prevention is the most effective approach to managing skin barrier concerns. To minimize potential, consider initiating sound strategies and management to mitigate the impact of environmental exposures that may be harmful to the skin and skin barrier:

• Education and knowledge—recognize and be aware of exposome triggers.
• Be observant of your exposures and how to minimize them.
• Evaluate internal and external oxidative support against ROS and free radical damage—topical antioxidants, nutrient-dense foods, supplements.
• Protection—SPF, blocking devices (eyeglasses, screens, etc.)
• Your primary focus? Maintaining functional integrity of the skin.
• Avoid barrier-disruptive agents (surfactants, acids, etc.)
• Subscribe to proven, research-backed ingredients that support the skin barrier and skin homeostasis.

References

1. https://onlinelibrary.wiley.com/doi/10.1002/imt2.50
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC7769076/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC10861303
4. https://www.skininc.com/science/physiology/article/22943858/the-skin-barrier-lipids-and-the-microbiome
5. https://link.springer.com/article/10.1007/s00441-014-2037-z
6. https://www.sciencedirect.com/science/article/pii/S0022202X15303560
7. https://www.ncbi.nlm.nih.gov/books/NBK470464/
8. https://www.mdpi.com/1422-0067/22/21/11676
9. https://www.dsm.com/content/dam/dsm/personal care/en_us/documents/trends/trendsinternational_journal_of_cosmetic_science_revealing-the-secret-life-of-skin.pdf

1. https://www.skininc.com/science/physiology/article/21879719/the-microbiome-gateway-to-the-skins-ecosystem
2. https://www.mdpi.com/1422-0067/24/13/10502
3. https://davidsuzuki.org/living-green/dirty-dozen-cosmetic-chemicals-avoid/
4. https://davidsuzuki.org/science-learning-centre-article/whats-inside-counts-survey-toxic-ingredients-cosmetics/
5. https://www.mdpi.com/1422-0067/24/13/10502
6. https://www.researchgate.net/publication/391768837_Facial_Dermatoses_in_E-Cigarette_Users_and_the_Role_of_Nicotine-Induced_Oxidative_Stress
7. https://ww2.arb.ca.gov/resources/fact-sheets/cleaning-products-indoor-air-quality
8. https://www.skininc.com/science/physiology/article/21878040/ozone-the-air-down-here
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC10519937/pdf/41598_2023_Article_42629.pdf
10. https://www.researchgate.net/publication/270657061_Potential_Health_Effects_Associated_with_Dermal_Exposure_to_Occupational_Chemicals