Back to basics: Skin interactome

When it comes to understanding the skin – and our bodies in general – we need to take a holistic view of the complex set of interactions that feed into the condition and functioning of our various biological systems and tissues.

‘Multi-omics analysis’ is one such research approach for assessing and monitoring the state of an individual’s physical condition, where datasets for different ‘omic’ groups – such as ‘genomics’ – are combined to understand the drivers of health or disease. For our skin, for example, factors such as skin health and aging can be assessed by looking at three key influences: the genome, exposome and microbiome.

As well as the independent influence of each of these factors, a key part to understanding their effect is building a picture of how they interact. This is known as the integrated ‘genome–microbiome–exposome’ effect, or the ‘interactome’.

In addition to providing a picture of each individual’s skin condition, the information gained from multi-omics analyses can help define the best recommendations for lifestyle changes, such as nutritional adjustments and personalized beauty routines, to help support skin health…

When it comes to understanding the skin – and our bodies in general – we need to take a holistic view of the complex set of interactions that feed into the condition and functioning of our various biological systems and tissues.

The interactome in skin health and aging

In this piece, we will run through the different components of the interactome, outlining why each is important and how they interact to influence skin health and aging [1].


The genome refers to internal factors, such as genetics and age, and gender, all of which can affect the condition of our skin.

Genetics. Ethnicity, for example, is a key genetic trait as the skin aging process manifests differently across diverse ethnic populations [2]. This is due to variances in factors such as stratum corneum and dermis composition (outer and inner layers of our skin, respectively), elasticity, collagen, transepidermal water loss (TEWL; find an explanation within here) and pigment levels [3,4,5]. Put into practice, research has shown that wrinkles appear at early stages in caucasian individuals compared to other ethnic groups. Asian and dark skin tones, for example, have much thicker and structurally more compact dermis [3], and the stratum corneum of darker skin types exhibits a higher lipid content and more cornified cell layers compared to the lighter skin [4] – all of which are factors thought to contribute to lower incidence of facial wrinkles in Asian and dark skin tone individuals.

Age and gender. Age and gender-specific hormones and other biological or physiological factors play an important role in skin morphology and the aging process. One interesting hypothesis, for example, links an accelerated skin aging process to excessive levels of iron and ferritin in menopausal women. Females lose excess iron through blood loss and skin shedding as part of the menstrual cycle, but post menopause the skin stores the excess iron in ferritin form. This accumulation of iron exacerbates the amount of reactive oxygen species – highly reactive chemicals – in the skin, possibly accelerating skin aging [6].


The exposome refers to external influences, such as environmental factors and lifestyle habits [7].

Environmental factors. The sun, pollution and climate are all examples of factors that affect our skin. When it comes to the sun, different types of light – including ultraviolet (UV), visible and blue light – all have an effect. UV is the primary factor of extrinsic skin aging, accounting for approximately 80% of facial aging [8,9] as UV rays can reach the skin’s deepest layers and induce undesirable changes in the dermis that lead to photoaging. Visible light can also cause reductions in collagen [10], and blue light has been shown to disrupt circadian rhythm and damage skin cells, eventually accelerating aging [11].

As the skin is the barrier between the rest of the body and its environment, it is also not surprising that seasonal variations and climate change also have a dermatological impact. Research has shown that generally, pigmentation and wrinkles are reduced in the winter compared to the summer, while other features such as skin barrier and moisture levels worsen [12]. Drier environmental conditions increase the permeability of the epidermis [13], and cold temperatures and dry conditions have been linked to a higher rate of skin irritations [14]. Furthermore, it has been outlined that sebum levels are generally higher in younger patients and during warmer months [15] – also highlighting an interactive additive effect of the genome and exposome on skin condition.

Lifestyle factors. As well as the outside environment, lifestyle habits such as sleep, exercise and diet, and emotional balance also need to be accounted for.

Sleep is important for growth and renewal of multiple physiological systems, with an acute lack of sleep shown to degrade the skin barrier and reduce hydration, elasticity, pores, translucency, brightness and blood flow [16].

Exercise and diet also have important skin health and anti-aging effects. During exercise, oxygen and nutrient-rich blood are delivered across the body due to the resulting blood flow dynamics [17], and sweating helps to keep skin clear as it flushes toxins from our pores that can otherwise lead to irritation and blemishes [18]. Vitamins, minerals and antioxidants, carotenoids, polyphenols, fatty acids and ceramides are all essential to include in our diet to support healthy skin. Vitamin C, for example, is broadly used as a supplement and has multiple benefits for our overall health [19], including acting as an antioxidant that drives skin photoprotection and reduces pigmentation, and improving the stability of the skin collagen protein.   

Maintaining an emotional balance is another factor that has been shown to improve skin condition. It is now well-known that there is a significant association between stress and an individuals’ health, including a negative impact on many dermatological diseases [20]. One cross-sectional study using medical students as subjects showed that older age, female gender and being in an exam week were associated with the highest perceived stress levels and associated with oily, waxy patches or flakes on scalps, dry/sore rashes, warts, pimples and itchy skin, among other symptoms [21] –again demonstrating the interacting genome and exposome.  


Finally, we come to the microbiome. Our skin microbiota – the living ecosystem of microbes on our skin’s outer barrier – plays an important role in maintaining skin condition and health, and is largely affected by both the genome and exposome.

In aging skin, for example, physiological changes, such as pH, lipid composition and sebum secretion, can impact skin microbiome composition. One study observed higher diversity in microbial species in people within an older age group relative to younger groups, with the most significant differences observed in samples from the cheek and forehead [22].

On the exposome side, air pollutants are one factor shown to impact the microbiome. When comparing subjects living across two cities of varying levels of pollution in China, for instance, a reduction in friendly bacteria was observed in those exposed to higher pollution levels, to the benefit of pathogenic bacteria that are associated with poor skin condition [23]. Cosmetics and personal care items are another example – products such as deodorants, foot powders and skin lotions have been shown to change the diversity of the bacteria on our skin, and to modulate the interlinked chemical diversity. The effects can last for weeks and produce highly individualized responses that manifest in differences in skin microbiome structure and dynamics, and in traits such as steroid and pheromone levels [24].

Following the concept of the interactome, the microbiome can therefore also feed into the impacts of genome and exposome effects on our skin – both to extenuate and mitigate. For example, the effect of UV on skin health and immune function can be modulated by certain members of the skin microbiota creating an anti-inflammatory environment [25]. The skin condition atopic dermatitis is also thought to be influenced by the presence of certain microbes as a result of childhood-associated skin bacteria (such as Streptococcus) being replaced by adult-associated bacterial species (Propionibacterium and Corynebacterium) during puberty [26], and research has demonstrated potential for protective microbes to help combat and reduce the effects of an array of other skin conditions.

Different perspectives. Interestingly, the inter-dependent relationship between the exposome and microbiome has led some to consider the microbiome as part of the exposome. For example, when it comes to the gastrointestinal exposome, one group of researchers suggest that this includes the physical components integrated with the mucosal microbiome, both of which are fundamental to gut physiology and disease across the whole human lifespan [27]. The mucosal network, which is responsible for maintaining the physiological state and functioning of our gastrointestinal system and other organs, also contributes to the maintenance of the microbiome and host integrity, working to stabilize composition and diversity of the gut and intestinal microbiome in an integrated manner.

Influencing our own interactome  

Gaining an understanding of the three components of the interactome can also be useful when it comes to influencing and nurturing our own skin. Although the impacts from our genetic traits tend to be harder to control, day-to-day strategies can be used to balance the influence of the exposome and microbiome to provide to preserve good skin health and protect against skin aging.

A daily skincare regimen, for example, involves the use of exposomic factors in the form of personal care products to support skin health and anti-aging by protecting against the negative effects of the interactome. This could involve ingredients such as microbiome-boosting pre, pro and postbiotics (see here) to not only support our day-to-day skin condition, but also to help manage symptoms and progression of dermatological issues such as acne and pruritus [28, 29].

However, extensive skincare routines and use of the wrong products can hinder the microbiome and worsen our skin’s condition, so it is crucial to be wary of what we put on our skin. The use of some cosmetics can alter skin bacterial diversity and contribute to the creation of dysbiotic (imbalanced) microbiota, with the overgrowth of certain bacteria at the expense of others [24]. For example, microbial dysbiosis can increase the prevalence of opportunistic bacteria such as Staphylococcus aureus, the elevation of which is associated with atopic dermatitis and several other several skin conditions [30].

Modifications of the skin microbiota can also trigger acne spots due to increases in some types of the bacteria Cutibacterium acnes, particularly in zones rich in sebum, consequently triggering inflammation [1]. But it is important to keep in mind that not all C. acnes bacteria are harmful for the skin. For instance, some strains have been shown to secrete ‘RoxP’, a beneficial antioxidant for human skin [31].

The future of the interactome

Our skin therefore is largely affected by the genome, exposome and microbiome, through a complex set of interactions between these three components.

There remains an incredible number of knowledge gaps – for example in the areas of sleep, diet and cosmetics – that require additional investigations to build a full picture of these complex interactions, but continued research into the skin interactome concept will allow us to better understand the molecular activity underlying skin health and aging.

Such investigations will help researchers to further develop skin treatment strategies to balance the influence of the exposome and microbiome to protect the skin. The work could also help us to understand epigenetic processes (which regulate how our genes are expressed), and may even offer the possibility to beneficially manipulate these pathways when it comes to aging…

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