In recent years, increasing attention has been paid to the best possible understanding of the human microbiome, which consists of the microbiota of individual organs and systems. The gut and human skin microbiota and their interactions with the host organism are particularly noteworthy. A growing body of scientific data indicates that the composition of commensal microorganisms living in or on the human body determines the maintenance of homeostasis and protects against the development of inflammation and the onset of many diseases, such as acne vulgaris. This article reviews the available information on the human skin microbiota, its function, composition, and variability depending on many factors and functions in a healthy body, as well as its influence on the development of acne vulgaris.
Human skin provides a convenient niche for microorganisms to inhabit. Therefore, the discussion of the structure and function of the microbiome must be linked to the structure and function of human skin (Fig. 1).
General plan of human skin structure; created with Biorender.com
Human skin, the body’s largest organ, is the body’s outer covering. Its surface area in an adult human is 1.5–2 m2, and its weight, including subcutaneous tissue, is about 18–20 kg (of which the epidermis alone weighs about 0.5 kg, and the dermis weighs 3 kg) (Lee et al., 2019). Different areas of the skin differ in terms of the thickness of the epidermis, the distribution of appendages in it, and the humidity and temperature on its surface (Sfriso et al., 2020). The total thickness of the facial skin measures 0.3–4 mm, and its surface is covered by a hydro-lipid mantle, a mixture of intrinsic and extrinsic fats, water, and exfoliated keratin (Kolarsick et al., 2011; Oh et al., 2016; Marks and Miller, 2019). The variable characteristics of the skin significantly affect the species composition and quantity of the microbiota (Scharschmidt and Fischbach, 2013; Gallo, 2017). It is important to remember that bacteria, viruses, fungi, and mites inhabit it. Most microorganisms inhabiting the skin are harmless, and function in symbiosis with skin cells, and interactions between microorganisms and skin cells include such phenomena as mutualism, parasitism, or commensalism (Belkaid and Segre, 2014). The skin performs many important functions, such as a protective barrier against environmental factors. Moreover, its proper functioning enables the body to maintain water-electrolyte balance and a constant body temperature, enabling the proper functioning of internal organs (Ladizinski et al., 2014). The skin contains numerous receptors and nerve endings that enable communication with the outside world, the reception of stimuli, and the functioning of the sensory organ (Kanitakis, 2002; Wolski and Kędzia, 2019). The skin also contains Langerhans cells, or immune system cells, so one of its functions is to receive and transmit immune signals and protect the body from pathogens (Chu, 2008). In the macroscopic structure of the skin, we can observe three layers: the epidermis, dermis, and subcutaneous tissue(Kanitakis, 2002; Orłowski et al., 2008). The epidermis is the outermost part of the skin, is 0.05–1.5 mm thick (the variation in thickness depends on the anatomical area), and comprises several layers of epithelial cells (Kanitakis, 2002; Wolski and Kędzia, 2019). The basal layer of the epidermis is considered the deepest layer, which includes dividing keratinocytes, melanocytes (pigment cells), and Langerhans cells (immune cells). The basal layer of the epidermis is also often called the reproductive layer. The next layer is the squamous layer, which consists of several rows of polygonal cells that, going gradually toward the surface, become progressively flattened. It is the thickest layer of the epidermis, comprising up to 12 rows of cells. Resistance fibers can also be distinguished in their structure, so the system created in this layer cushions pressure and stretching (Orłowski et al., 2008). Thus, in the next layer, the granular layer, only spindle-shaped cells with an atrophic cell nucleus and numerous granules of keratohyalin rich in calcium are observed (Fairley et al., 1991). In the granular layer, 1–4 rows of cells are usually observed (Orłowski et al., 2008). The light layer is characteristic only of the epidermis of the palms of the hands and soles of the feet. The last, or most superficial layer, is the stratum corneum, which consists of corneocytes and flattened keratinized cells that attack cell nuclei (Sanmiguel and Grice, 2015). Corneocytes undergo gradual exfoliation, and the cycle of permanent epidermal cell renewal, or epidermal transition, lasts 28 days and increases with age to about 30–31 days (Matoltsy, 1976; Voegeli and Rawlings, 2023) The entire epidermal cycle is considered to be the proliferation and differentiation of cells in the basal layer, their further transformation and movement toward the more superficial layers, the gradual extinction of the cell nucleus and eventually reaching the stratum corneum and replacing older cells (Chu, 2008; Prescott et al., 2017; Marks and Miller, 2019). The above-described arrangement of epidermal cells makes the epidermis a hostile environment for microbial growth. The surface of the epidermis is mostly dry, rough, and constantly flaking off (Chu, 2008; Voegeli and Rawlings, 2023). Removing cells in the stratum corneum allows regular removal of microorganisms from the skin surface, preventing their unrestricted growth and biofilm formation on the skin surface (Kolarsick et al., 2011). The multilayer nature of the epidermal cells, their various cell arrangement and shapes, as well as their interconnectedness (which disappears only in the superficial horny layers), as well as the presence of the hydro-lipid mantle, prevents the loss of water and skin essential products. It prevents the entry of harmful compounds and microorganisms from the environment. Moreover, the presence of the hydro-lipid mantle causes acidification of the environment to a pH value of 4 to 6.5 (Caputo and Peluchetti, 1977; Schmid-Wendtner and Korting, 2006). It also contains antibacterial compounds such as sebum, lysozyme, and dermicidin. Keratinocytes, sebocytes, sweat gland cells, and mast cells have the properties of secreting antimicrobial agents. According to modern studies, about 20 peptides with antimicrobial activity on the skin surface are called AMPs (antimicrobial peptides) (Jungersted et al., 2008). AMPs include cathelicidins, defensins (HBD1, HBD2, HBD3), psoriasins, antimicrobial RNase 7 protein, and SLPI protein (Cogen et al., 2010; Adamczyk et al., 2018). The above allows the skin to be colonized only by specific microorganisms and strictly controls their abundance (Scharschmidt and Fischbach, 2013; Belkaid and Segre, 2014; Flowers and Grice, 2020). Notably, the epidermis is non-vascularized and draws nutrients only from the superficial vascular plexus of the dermis. The dermis, conversely, comprises connective tissue, containing cells called fibroblasts, collagen and elastic fibers, blood vessels, and skin appendages such as hair, sweat, sebaceous glands, sensory receptors, and nerve endings (Marks and Miller, 2019). A distinct boundary known as the dermal-epidermal boundary can be observed at the junction of the basal layer of the epidermis with the dermis (Kanitakis, 2002). Within the dermis, two layers can be distinguished: the papillary layer (more superficial) and the reticular layer (deeper layer). The papillary layer’s papillae push into the structure of the epidermis while preventing the epidermis layers from moving against each other. Conversely, the reticular layer has numerous collagen and elastin fibers strands, with tiny fibers and nerve endings, connective tissue cells, hair, glands, and smooth muscle cells forming the adnexa muscles. Numerous blood and lymphatic vessels can also be observed in its structure (Sanmiguel and Grice, 2015). The deepest layer is the subcutaneous tissue, mainly composed of loose connective tissue and adipose tissue; its overriding function is to connect the dermis to deeper structures. This layer has glue-like and elastic fiber chambers filled with adipose tissue, making it possible to cushion damage and absorb significant water. The subcutaneous tissue also has blood vessels, lymphatic vessels, nerve fibers, and glands. Located within the dermis and subcutaneous tissue, the venous, arterial, and lymphatic vessels form the vascular system of the skin. Its characteristic features are the delicacy and small caliber of the vessels, as the larger ones are located directly in the muscles. Due to their small size, the network of dermal vessels is very dense and strongly developed, reaching under the papillary layer of the dermis, thus enabling proper nourishment of the epidermal cells (Wolski and Kędzia, 2019). Hair follicles and sweat glands have separate vascular plexuses conditioning their proper functioning (Kolarsick et al., 2011).
For the skin to function correctly, it must maintain its physiological pH at 4.0–6.5 (Adamczyk et al., 2018). The pH value within these limits protects the body from harmful chemicals, bacteria, fungi, or viruses (Orłowski et al., 2008). The pH value of the skin allows the growth of only those microorganisms that tolerate well a slightly acidic pH (Wolski and Kędzia, 2019). Therefore, it can be deduced that the guard against pathogens is the intact stratum corneum, the drying process of the skin surface (as it has been proven that the number of bacteria is reduced faster on dry skin), and the acid reaction of the lipid mantle, which is conditioned by the proper work and function of the screen sweat glands containing lactic acid and fatty acids (Schmid-Wendtner and Korting, 2006; Jungersted et al., 2008; Kolarsick et al., 2011; Percival et al., 2012; Adamczyk et al., 2018; Wolski and Kędzia, 2019).
Skin microbiota is a set of microorganisms, mainly bacteria, that form a complex ecosystem on the skin’s surface in a given habitat (Sanford and Gallo, 2013) (Fig. 2). This microbiota may also include some fungi (Condrò et al., 2022). Viruses and parasites, however, are always considered pathogens (Scharschmidt and Fischbach, 2013; Malinowska et al., 2017; Sinha et al., 2021). The qualitative and quantitative composition of the cutaneous microbiota is variable. It depends on many factors such as temperature, pH, humidity, nutrient availability, oxidoreductive potential, the climatic zone in which a person lives, race, sex, age, hormones, diet, body weight, susceptibility to stress, type of clothing worn, humidity in a particular region of the body, level of hygiene, immune status of the organism, past diseases and their treatments, antibiotic therapy used or work performed (Costello et al., 2009; Belkaid and Segre, 2014; Boxberger et al., 2021). How a person’s skin is built, and functions determines its microbiome’s stability in terms of composition, abundance, and resistance to change (Sanmiguel and Grice, 2015; Malinowska et al., 2017; Lee et al., 2019). On the other hand, skin microbiota has a specific role in maintaining skin homeostasis (Table I). Unfortunately, the complete species composition of the skin microbiome is not yet fully understood. Limited diagnostic capabilities are the most likely reason for incomplete knowledge on this subject (Adamczyk et al., 2018; Sinha et al., 2021).
Composition of the skin microbiota; own graphic inspired by Smythe and Wilkinson, 2023
Eight proposed roles of skin microbiota
| The role of the skin microbiota |
|---|
| 1. Maintaining the acidic pH of the skin (pathogenic microorganisms prefer a more alkaline pH), |
| 2. Prevent settlement and multiplication of pathogenic bacteria by limiting the available food supply (colonization resistance) |
| 3. Keeping the commensal biota intact and eliminating disease-causing microorganisms through the production of antibacterial substances |
| 4. Maintenance of the proper functioning of the epidermal barrier |
| 5. Participation in metabolic processes |
| 6. Impact on the process of tissue maturation in human individual development |
| 7. Maintaining the homeostasis of the immune system by modulating the innate immune response and influencing the development of the acquired response |
| 8. Regulation of pro-inflammatory cytokine expression and activation of the complement system |
The number of microorganisms in the skin of a healthy person is 104–105 cfu/cm2. There are four main types of bacteria inhabiting human skin: Actinobacteria (Corynebacterium spp, Cutibacterium spp., Microbacterium spp., Micrococcus spp.), Firmicutes (non-hemolytic aerobic and anaerobic staphylococci (Staphylococcus spp.), Clostridium spp, a-hemolytic streptococci (Streptococcus spp.) and enterococci (Enterococcus), Bacteroidetes (Sphingobacterium spp., Chryseobacterium spp.) and Proteobacteria (Janthinobacterium spp., Serratia spp., Halomonas spp., Delftia spp., Comamonas spp.) (Cogen et al., 2008; Sanford and Gallo, 2013; Scharschmidt and Fischbach, 2013; Schommer and Gallo, 2013; Wang et al., 2014; Dreno et al., 2017; Prescott et al., 2017; Condrò et al., 2022). In a healthy human, the natural skin microbiota can be divided into permanent (renewable) and transient (temporary) (Omer et al., 2017). The permanent microbiota includes Gram-positive bacteria, mainly coagulase-negative staphylococci – Staphylococcus epidermidis (estimated to account for 50% of the bacteria residing on the skin and inhabiting the higher areas of the hair follicle mouths) and Streptococcus spp. and Enterococcus spp. and Gram-positive bacilli Corynebacterium spp. (mainly C. jeikeium), Brevibacterium spp., Cutibacterium acnes (Cogen et al., 2008; Dréno et al., 2018; Claudel et al., 2019; Xu and Li, 2019; Brown and Horswill, 2020; Flowers and Grice, 2020). The skin surface also hosts S. saprophyticus, S. hominis, S. warneri, S. haemolyticus, and S. capitis (Dreno et al., 2017). Bacteria of the genus Micrococcus are also isolated from the skin surface, most notably M. luteus and the less abundant M. varians, M. lylae, M. sedentarius, M. roseus, M. kristinae and M. nishinomiyaensis (Carmona-Cruz et al., 2022). These bacteria belong to symbiotic species and are the most stable part of the skin microbiome (Grice et al., 2008; Sanford and Gallo, 2013; Belkaid and Segre, 2014; Sanmiguel and Grice, 2015; Adamczyk et al., 2018; Lee et al., 2019; Condrò et al., 2022). Although Cutibacterium acnes is one of the main commensals of the normal bacterial biota, it also contributes to the pathogenesis of acne vulgaris (Dessinioti and Katsambas, 2017; Dréno et al., 2018). However, contrary to previous thinking, acne vulgaris is not associated with excessive proliferation of C. acnes. Present at low levels on the skin surface, C. acnes is the predominant bacterial species inhabiting sebaceous follicles (Omer et al., 2017). In contrast, studies conducted by Byrd et al. on healthy volunteers also confirm the presence of Enhydrobacter spp. and Veillonella spp. (Byrd et al., 2018). On the other hand, Myles et al. in their study focused on Gram-negative bacterial cultures and identified the following microorganisms: Roseomonas mucosa, Pseudomonas spp., Acinetobacter spp., Pantoea septica and Moraxella asloensis as commensally resident on human skin (Myles et al., 2018). Other studies have confirmed that Gram-negative bacteria, including Enterobacteriaceae, non-fermenting Gram-negative bacteria, and anaerobes, are marginal. Still, commensal organisms are also part of the transient fraction of the skin microbiota. The permanent skin microbiota also includes Micrococcus luteus, Staphylococcus aureus, Candida spp. Micrococcus and Staphylococcus bacteria habitually colonize the surfaces of the stratum corneum, while aerobic and anaerobic lipophilic tentacles abundantly colonize the deeper parts of the hair follicles and sebaceous glands (Myles et al., 2018; Boxberger et al., 2021). The secretion of skin glands modifies the composition of the solid microbiota, the way of dressing, or the vicinity of mucous membranes (Adamczyk et al., 2018; Prast-Nielsen et al., 2019; Carmona-Cruz et al., 2022). Corynebacterium, Micrococcus, Cutibacterium (formerly Propionibacterium) microorganisms are classified as Actinobacteria, which are Gram-positive microorganisms that produce numerous antibiotics (Scharschmidt and Fischbach, 2013; Condrò et al., 2022). Actinobacteria account for 51.8% of all isolated microorganisms from human skin (Schommer and Gallo, 2013; Lee et al., 2019). They are observed on the skin of the face, including the ears and nose, on the neck, back, lower abdomen, and feet. Fungi of the genus Malassezia quantitatively account for about 80% of all fungi described on human skin, but their number depends on the anatomical location of the human body (Prohic et al., 2016; Adamczyk et al., 2018; Claudel et al., 2019; Xu and Li, 2019; Carmona-Cruz et al., 2022). Fungi also include the Candida albicans, but also Rhodotorula rubra, Trichosporon cutaneum, Aspergillus spp., Penicillium spp., Rhizopus spp., Microsporum gypseum. These organisms are considered symbiotically mutualistic or commensals, i.e., organisms that do not harm the human organism and even benefit it (Adamczyk et al., 2018). Their very presence limits the growth of other (often harmful) organisms by competing with them (Grice et al., 2008; Sanmiguel and Grice, 2015). The transient microbiota is periodically variable and associated with continuous exposure and direct contact of the skin with the external environment (it can come from other people, animals, or the environment).
The natural biota of the skin should not be destroyed, and the abundance of bacteria and fungi must remain in balance (Adamczyk et al., 2018). Therefore, the overriding role of the skin microbiota will be to maintain skin homeostasis in a healthy person, fighting potential pathogens and adverse external environmental factors. It is one of the mechanisms that ensure the proper barrier function of the skin (Claudel et al., 2019; Carmona-Cruz et al., 2022). Moreover, skin bacteria secrete protease enzymes involved in the exfoliation and renewal of the stratum corneum. The sebum and free fatty acids produced are involved in regulating skin pH. Bacteria also produce lipase enzymes that break down superficial lipid layers (Flowers and Grice, 2020). Ureases, in turn, are responsible for the proper breakdown of urea as a secondary metabolite (Jungersted et al., 2008). The cutaneous microbiota protects its host from potentially pathogenic agents by competing with them and producing antimicrobial peptides (AMPs) (Cogen et al., 2010; Sanford and Gallo, 2013; Prast-Nielsen et al., 2019; Flowers and Grice, 2020; Bonar et al., 2021). Some bacteria produce bacteriocins that kill pathogens or produce substances that are bacteriostats, which hinder the division and multiplication of pathogens (without being harmful to the organisms producing them) (Adamczyk et al., 2018). For example, the bacterium Staphylococcus epidermidis produces an antimicrobial peptide that destroys Staphylococcus aureus bacteria (Brescó et al., 2017; Brown and Horswill, 2020). Another commensal bacterium, Cutibacterium acnes, can inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) by fermenting glycerol into a series of short-chain fatty acids, which lowers the intracellular pH and inhibits the growth of Staphylococcus aureus (Platsidaki and Dessinioti, 2018; Spittaels et al., 2020; Bonar et al., 2021). Studies have shown that S. epidermidis is detected by keratinocytes through Toll-like receptor 2 (TLR2), thereby increasing host resistance to S. aureus infection through increased expression of antimicrobial peptides (defensins) (Strunk et al., 2010; Scharschmidt and Fischbach, 2013; Sanmiguel and Grice, 2015; Brescó et al., 2017; Dreno et al., 2017). Studies by Wanke et al. confirm that bacteria are also involved in mast cell-mediated antiviral protection (Wanke et al., 2011). TLR2 activation increases the number of mast cells activated for antiviral protection in the skin (Hooper et al., 2012; Schommer and Gallo, 2013; Brown and Horswill, 2020). Fungi of the genus Malassezia, on the other hand, produce several indoles that inhibit the growth of unwanted yeasts and molds (Prohic et al., 2016).
Host-microbiota interactions; own graphic inspired by Liu et al., 2023
Relationships between constantly occurring microorganisms, those transient and pathogenic, are highly complicated and still widely studied. It turns out that it is not only the adequately composed microbiota of the skin that guards safety but also the reciprocal numerical ratio of the different types of microorganisms to each other that matters (Lee et al., 2019). It is also worth remembering that microorganisms protect against infections and are responsible for a given person’s smell (Flowers and Grice, 2020).
It is worth mentioning that skin commensal bacteria have a close relationship with the immune cells of their host, and T lymphocytes are taught from the beginning to respond to signals produced by skin commensals. For example, Staphylococcus epidermidis produces a particular type of acid that can bind to specific receptors, activating the immune system and an influx of T lymphocytes into the skin despite the absence of inflammation. T lymphocytes, in turn, promote the proliferation of keratinocytes and accelerate wound healing (Scharschmidt and Fischbach, 2013; Belkaid and Segre, 2014; Flowers and Grice, 2020). In their study, Leonel et al. collected current knowledge regarding the involvement of commensals in wound healing. Unfortunately, the results of their observations somewhat confuse the reader (Leonel et al., 2019). For example, it was shown that the absence of commensal cutaneous microorganisms positively affects the wound-healing process. On the other hand, the positive effect of S. epidermidis, as an agent associated with unconventional repair mechanisms in wound healing through activation of CD8 regulatory T cells, has been demonstrated (Hooper et al., 2012; Leonel et al., 2019; Brown and Horswill, 2020). This finding was confirmed by Lai et al. However, the study results are heterogeneous, indicating the need for further research on the influence of the skin microbiota on the wound healing process (Lai et al., 2010). The presence of bacteria, especially S. epidermidis, promotes the strengthening of the skin barrier by increasing the number of tight junctions in skin cells. One study also showed that a specific strain of S. epidermidis can produce 6-N-hydroxyaminopurine (under the right conditions), which may be responsible for protection against skin cancer (Nakatsuji et al., 2018; Severn and Horswill, 2023). The skin, a physical barrier, allows the exchange of signals between the body and the external environment. It is also an immune barrier. Keratinocytes, or epidermal cells, constantly analyze what bacteria are on their surface. It is made possible by PRR – pattern recognition receptors – which detect the presence of molecules produced by bacteria, immediately alerting the body to pathogens on its surface. Activation of the receptors stimulates an immune response, which triggers the production of molecules that kill bacteria, viruses, and fungi (Severn and Horswill, 2023). Hence, the conclusion is that there is a constant flow of information between the skin microbiota, keratinocytes, and the immune system, enabling an immediate response to the presence of an unfriendly microbiota (Scharschmidt and Fischbach, 2013; Belkaid and Segre, 2014; Liu et al., 2023). Unfortunately, to date, the mechanisms of this communication have not been fully understood. However, it has been shown that resident bacteria interact with skin signaling molecules. Substance P, the primary skin neuropeptide modulated by pain, stress, or infection, is involved in the pathogenesis of many multifactorial skin diseases. Some of the effects of substance P are mediated through interactions with the skin microbiota. In particular, substance P can increase the virulence of staphylococci – it induces the secretion of enterotoxin C2 by Staphylococcus aureus and biofilm formation by S. epidermidis, which increases the adhesion of both bacteria to keratinocytes (Castillo et al., 2019). C. acnes variously modulates melanocyte survival while playing a role in the post-inflammatory pigmentation of acne lesions (Wang et al., 2014; Platsidaki and Dessinioti, 2018). Furthermore, the most recent and initial studies indicated that the interplay between skin microbiota and its host is not restricted to the immune system and may be affecting brain and cognitive function (Wang et al., 2024).
Microbial niches on the surface of the skin; created with Biorender.com, inspired by Byrd et al., 2018
The qualitative composition of the human microbiome is individually specific and varies by area of skin inhabitation (Costello et al., 2009; Sanford and Gallo, 2013; Sfriso et al., 2020). The observed microbial niches are determined by the thickness of the skin in different areas, anatomy – pits, depressions, or folds of the skin, as well as the different distribution of skin appendages, which have their unique microbiome (Lee et al., 2019; Flowers and Grice, 2020). It causes human skin to be divided into high-moisture areas, sebum-rich areas, and dry areas. More commensal microbiota are found in high-moisture areas than in dry areas. On the other hand, dry areas are more likely to have potentially invasive staphylococci, which require a less hydrated environment to grow (Sanford and Gallo, 2013). Bacterial growth is also affected by temperature (from 29.5°C on the fingers to 36.6°C in the armpit pits) and pH (from 4.2 on the cheeks to 7.9 in the armpit pits) (Costello et al., 2009; Adamczyk et al., 2018; Lee et al., 2019).
Skin microbiota composition depends on many factors (Sanford and Gallo, 2013; Sfriso et al., 2020; Smythe and Wilkinson, 2023). One of them is the site on the skin. In their study, Grice et al. analyzed 20 different sites on the human skin of 10 healthy patients. They proved that Cutibacterium and Staphylococcus predominated in sebaceous areas, while Corynebacterium species resided in the highest numbers in moist areas (Grice et al., 2008). On the other hand, a strongly mixed bacterial population was observed in dry areas, with a higher frequency of β-proteobacteria and Flavobacteria (Prescott et al., 2017). On the other hand, a study by Costello et al. showed much greater phylogenetic diversity at various sites on the skin compared to the microbiota of the gut, external auditory canal, or oral cavity. Ethnicity has also been shown to contribute to the diversity of the skin microbiota and is partly related to lifestyle (Costello et al., 2009). For example, differences in microbiota composition have been shown between individuals of East Asian and European or African descent (Harker et al., 2014). Significant differences are observed, for example, in the axillary region, where the abundance of Staphylococcus varies significantly concerning Corynebacterium (Cogen et al., 2008; Dréno et al., 2018; Flowers and Grice, 2020). The study by Perez et al. proved that the microbiota of the arm of African-American men is relatively homogeneous but significantly different from other ethnic groups. Similar conclusions were reached after studying the axillary microbiota of East Asian men; relative to the other ethnic groups, the microbial composition was quite different. What is more, East Asian individuals have a higher total amount of bacteria and proteobacteria relative to other groups (Perez et al., 2016). The distribution of Corynebacterium species was also analyzed, and it was found that Corynebacterium variabile is found only in Hispanics. In contrast, Corynebacterium kroppenstedtii is found only in the East Asian group (Boxberger et al., 2021). However, in this era of mass population migration, a complete definition of skin microbiota according to ethnicity is impossible. Physiological differences between male and female skin, such as different hormone levels, sweating rates, or skin surface pH, are also observed (Fierer et al., 2008). The most remarkable differences are observed in the hand microbiota of men and women. It has also been shown that a higher amount of Cutibacterium and Corynebacterium is found in men than in women (Lee et al., 2019). In contrast, bacteria from the Enterobacteriaceae, Moraxellaceae, Lactobacillaceae, and Pseudomonadaceae families are more abundant in women. Staphylococcus spp. occurs in significantly higher numbers in women than men, while Corynebacterium spp. is far more likely to colonize men’s skin (Grice et al., 2008; Perez et al., 2016; Boxberger et al., 2021; Robert et al., 2022). Observing the distribution of Malassezia species in studies conducted by Prohic et al., no significant sex effect was found (Prohic et al., 2016). Leung et al. showed that males had higher amounts of Cutibacterium, Staphylococcus, and Enhydrobacter, while Streptococcus was observed in higher amounts in the female population. The Epicoccum and Cryptococcus genera were found in higher amounts in sebaceous areas in men, while Malassezia was mainly observed in women (Leung et al., 2015). Li et al. observed that men have higher amounts of Corynebacteria, although the difference is insignificant (M. Li et al., 2019). However, only males host Corynebacterium amycolatum and Corynebacterium kroppenstedtii, while females only host Corynebacterium urealyticum and Corynebacterium variabile (C. Xi Li et al., 2019). It is also essential to look at the impact of the aging process on the composition of the skin microbiota. Indeed, aging is associated with many changes in skin characteristics and features, such as the appearance of spots and wrinkles and altered sebaceous gland activity, thereby affecting the composition of the skin microbiota. A study by Somboon et al. found a significantly higher prevalence of Plantomycetes and Nitrospirae bacteria in adolescents than in other age groups (Wilantho et al., 2017). On the other hand, senile individuals show a significantly lower amount of Cutibacterium compared to the other age groups and an increased amount of Corynebacterium and Acinetobacter (Dessinioti and Katsambas, 2017; Dreno et al., 2017). In older adults, there is also an increase in Proteobacteria and a decrease in Actinobacteria (Wilantho et al., 2017). Contemporary studies also show decreased sebum production with age, reducing available nutrients for commensal bacteria and an increased possibility of spreading opportunistic bacteria (Boxberger et al., 2021). Significant variation with age is also observed within Malassezia. For example, Malassezia furfur is characteristic of children’s trunk skin, while Malassezia restricta predominates on the scalp of individuals between the ages of 21 and 35. In older people, on the other hand, Malassezia sympodialis predominates (Prohic et al., 2016). Demodex spp. mites, studies show, are characteristic of older adults, and in the over-70 age group, they are found in up to 95% of (Adamczyk et al., 2018; Boxberger et al., 2021).
Mode of delivery, lifestyle, hygiene habits, cosmetics used, antibiotics used, geographic location, or climate can be considered external factors. In newborns, it has been indicated that the delivery type significantly impacts the skin microbiota composition. Babies born by natural childbirth have a skin microbiome shaped by bacteria present in the birth canal and the mother’s vaginal area. On the other hand, babies born by cesarean section will acquire a bacterial biota similar to that of the mother’s skin (Capone et al., 2011; Sfriso et al., 2020). The primary microbiota is transient and largely dependent on environmental factors. Later, it evolves to resemble the adult skin microbiota (Kong and Segre, 2017). During the first years of life, a highly differentiated skin microbiota develops, largely dependent on the child’s changing diet, increasing contact with people and animals, and exploring the environment. From 3 months, regionalization of the skin microbiota is observed in children (Dominguez-Bello et al., 2010; Nagata et al., 2012). Depending on the inhabited environmental zone (rural or urban), differences in the human skin microbiota related to the presence of pets are also observed. It is also worth mentioning the phenomenon of convergence of the skin microbiota in people who live together and are not related or do not have intimate relations. Studies also indicate that using facial makeup significantly increases the variability of commensal bacteria on human skin. Most cosmetics have preservatives in their formulation, which prevent the development of biofilm and the growth of Staphylococcus aureus or Cutibacterium acnes populations. Unfortunately, chemical compounds in cosmetics also inhibit the survival of commensal bacteria (Fournière et al., 2020). Emulsifiers, in turn, promote the growth of potential pathogens such as Staphylococcus aureus. The use of topical antibiotics also affects the composition of the skin microbiota, causing a significant decrease in commensal Staphylococcus spp. (Reid et al., 2011; Findley et al., 2013; Cooper et al., 2015; Baldwin et al., 2017; Wallen-Russell and Wallen-Russell, 2017). Recent studies have also shown increased benefits of living in an alpine climate compared to a maritime (which significantly impacts treating atopic dermatitis in children). However, this observation needs confirmation in people with healthy skin (Nakatsuji et al., 2013; van Mierlo et al., 2019). Other authors indicate that after exposure to seawater, exogenous bacteria were still present on the surface for at least 24 hours after swimming and that exposure to ocean water removed physiological bacteria from human skin (Nielsen and Jiang, 2019). Altitude, associated with extreme environmental conditions, has also been proven to have a detrimental effect on skin microbiota. Add to this air pollution, which reduces the diversity of skin microbial populations (Adamczyk et al., 2018).
Finally, active ingredients used in cosmetics can change the composition of the skin microbiome – they can promote or inhibit the growth of certain microorganisms. According to Cundell, moisturizers can reduce the intensity of water loss from the skin and promote the skin’s microflora, thereby reducing the exfoliation of dead skin cells (Cundell, 2018). Moreover, the lipid compounds of these cosmetics promote the growth of lipophilic bacteria (Staphylococcus and Cutibacterium) (Moskovicz et al., 2020). Unfortunately, studies also indicate that increased levels of skin hydration can reduce the number of Cutibacterium, as proven by Lee et al. in their research (Lee et al., 2018). It is also worth noting that bacteria can be used as active ingredients in cosmetics, mainly probiotic bacteria of the Lactobacillus genus (Butler et al., 2020). They show the ability to synthesize and secrete various antimicrobial substances and block pathogens’ adhesion to skin cells. However, it is essential to remember that improperly selected cosmetics for the skin type or skin problem and improper use of preparations can negatively affect the skin microbiome, reducing its diversity leading to dysbiosis (Andersen, 2019).
Based on the literature review, eleven factors affecting human skin microbiota are presented in Fig. 5.
Eleven factors contributing to changes in skin microbiota; own graphic
Due to its variability and susceptibility to many factors, the human skin microbiota still requires much research and a better understanding of its functioning. At the same time, its crucial role in organizing human health and preventing the spread of inflammation should be kept in mind. Skin commensals prevent the development of many skin diseases, such as acne vulgaris, atopic dermatitis, and rosacea. However, the variability of environmental factors makes it impossible to draw uniform conclusions about the exact composition of the skin microbiota in different age groups or the context of sex differences.