Modern tendencies of influence on skin microbiome by means of dermatocosmetics: practical aspects of probiotic bacteria application in the composition of biotic complexes

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INTRODUCTION

Over the past few decades, research on the microbiota and microbiome of living organisms has seen a rapid rise, and the role of microbial communities in maintaining human homeostasis and contributing to the pathogenesis of diseases has attracted considerable scientific and societal interest [1].

Currently, the term microbiome (from Greek Μικρος, meaning “small,” and Βιος, meaning “life”; the suffix “-ome” is an anglicized form of Greek) refers to the community of microorganisms (bacteria, viruses, fungi) inhabiting a specific environment, along with their genes and metabolites [2]. In contrast, the term microbiota (from Greek Μικρος, meaning “small,” and Βιοτα, meaning “life”) denotes the collection of living organisms from different kingdoms (prokaryotes such as bacteria and archaea; eukaryotes like protozoa and fungi) residing within a given ecosystem.

The human-associated microbial community is extremely abundant, estimated to comprise more than 3.8 × 10¹³ microbial cells [3], with the gut and skin microbiota exhibiting the highest diversity [3]. Bacterial cells form a collective functional domain, sometimes referred to as the “last human organ” [5]. The total gene content of microorganisms that constitute the microbiome is approximately 100 times greater than that of the human genome [4]. These microbial genes are involved in the regulation of host physiological processes, function as enzymatic proteins, and influence the production of various metabolites [6]. Microbial genes, along with structural components, metabolites, signaling molecules, and environmental conditions, establish specific environmental niches in the gastrointestinal tract, respiratory tract, urogenital tract, skin, and other body sites [1].

Microorganisms exist within complex communities, and their communication with each other and with human cells is critical for microbiota composition, its functional activity, and host health [7]. Interactions among microorganisms are mediated by small molecules known as autoinducers [8], whereas interactions with host cells occur through the secretion of antimicrobial substances (bacteriocins), short-chain fatty acids (acetic, propionic, teichoic, butyric, valeric, caproic acids, etc.), and other metabolites, exopolysaccharides, and cell surface proteins [9].

To date, the gut microbiota is the most extensively studied microbial community [10]. It is an integral part of human digestion, capable of generating nutrients from substrates inaccessible to host enzymatic processes. According to data from the Human Microbiome Project and the MetaHIT metagenomic database, approximately 3000 bacterial species have been isolated from human feces, classified into 11 different phyla, with Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes comprising more than 90% of the gut microbial community [11, 12]. The human skin microbiome is also highly diverse. It is suggested that the heterogeneity of skin microbiota may be comparable to that of the gut [13]. Alterations in the skin microbial community are closely associated with skin aging and the pathogenesis of chronic inflammatory dermatoses, such as acne, rosacea, and psoriasis [14–16].

Like the gut microbiota, the skin microbiota can serve as a target for modulation in cases of dysbiosis, and for developing therapeutic strategies for skin disorders associated with significant microbial alterations [17, 18]. In recent years, strategies have been developed to normalize the skin microbial composition using either live or inactivated bacteria or their lysates [17]. These lysates contain bacterial cell wall components, bacteriocins, short-chain fatty acids, signaling molecules, and metabolites [17, 19, 20], and can be incorporated into topical formulations, including dermatocosmetic products.

SKIN BIOTA–TISSUE COMPLEX AND ITS FUNCTIONS

Skin is one of the largest human organs [21] and performs a wide range of functions, the most important of which is its barrier and protective role. To fulfill this role, the skin establishes physical, chemical, and neurosensory barriers and exerts multiple immune and neuroendocrine functions. The skin microbial community actively participates in these processes, and close functional and morphological interactions exist between microbiota cells and skin cells—keratinocytes, immune cells, mast cells, and melanocytes [22]. The combination of the microbiota, its metabolites, and the structural elements of the skin forms the skin biota–tissue complex, which maintains the physiological functions of the skin [18].

The human skin microbiota comprises bacteria, archaea, fungi, viruses, and mites. Bacteria are the most abundant kingdom on different skin sites, whereas fungi are the least numerous [23]. The vast majority of commensal bacterial species of skin belong to four major phyla: Actinobacteria (Corynebacterium, Propionibacterium, Cutibacterium, Micrococcus, Actinomyces, Brevibacterium), Firmicutes (Staphylococcus, Streptococcus, Finegoldia), Proteobacteria (Paracoccus, Haematobacter), and Bacteroidetes (Prevotella, Porphyromonas, Chryseobacterium) [24].

The composition of the skin microbial community primarily depends on the morphophysiologic characteristics of distinct skin areas. The variability of bacterial composition is determined by so-called moist (major folds, popliteal fossae, flexural surfaces of elbows, feet), dry (forearm, lower leg), and sebaceous (scalp, face) zones [22]. Differences between bacterial communities from distinct skin niches may even exceed those between individuals. Lipophilic Propionibacterium species dominate in sebaceous areas; Staphylococcus and Corynebacterium prevail on moist skin, whereas Proteobacteria and Flavobacteriales dominate on dry sites [13]. In contrast, the fungal community composition is relatively uniform across most body surfaces, with minor variations. For example, Malassezia species predominate on the trunk and extremities, whereas the feet also harbor Aspergillus spp., Cryptococcus spp., Rhodotorula spp., Epicoccum spp and other genera [25].

To survive on the skin surface, microorganisms have adapted to utilize components of sebum, sweat, and the stratum corneum. For instance, Propionibacterium/Cutibacterium acnes (P/C. acnes) secretes proteases that release arginine from stratum corneum proteins and lipases that hydrolyze sebum triglycerides, generating free fatty acids that facilitate microbial adhesion to the skin [26]. Lipids from sebum and the stratum corneum are also utilized by Corynebacterium and Malassezia fungi. These microorganisms are unable to synthesize their own lipids: the former use host-derived lipids to produce corynemycolic acids that coat their cell surface, whereas the latter exploit them as a nutrient source [27].

The functions of the skin microbiome are diverse and not yet fully understood. They include involvement in the formation and maintenance of the microbial, chemical, immune, neurosensory, and physical barriers of the skin [28, 29]. Commensal microorganisms can synthesize and secrete a broad range of signaling molecules and biologically active compounds exerting various regulatory effects (see Table 1) [19, 22]. For instance, certain Staphylococcus epidermidis strains secrete bacteriocins that inhibit S. aureus growth; lipopeptides that enhance keratinocyte production of antimicrobial peptides; 6-N-hydroxyaminopurine with potent antioxidant properties; and factors that activate interleukin (IL)-1 signaling pathways in CD8⁺ skin cells or induce immunologic tolerance toward autoantigens and microorganisms [19].

 

Table 1. Human skin microbiota functions

Barrier function	Major mechanisms
Microbial	Competitive elimination of pathogens
	Production of bacteriocins, antimicrobial peptides, lantibiotics, and virulence factors that suppress other bacteria: • S. epidermidis secretes epidermicin, which inhibits  S. aureus → PCMγ and PCMδ suppress S. aureus, P/C. acnes,  Streptococcus spp., → Serine protease Esp inhibits S. aureus biofilm formation • S. lugdunesis secretes lugdunin, which inhibits S. aureus • S. hominis secretes sh-lantibiotics, which inhibit S. aureus • S. capitis secretes PCMγ, which inhibits S. aureus, P/C. acnes, and Streptococcus spp. • P/C. acnes secretes cutimycin • Corinebacterium spp. inhibit S. aureus and Streptococcus spp.
Chemical	Production of lipases
	Cleavage of free fatty acids
	Formation of the acid mantle: • Sapienic acid regulates microbial colonization • Lauric acid inhibits pathogenic bacteria • Myristic acid exerts antibacterial effects • Lipoteichoic acid suppresses excessive activation of proinflammatory signaling pathways
	Stimulation of β-defensin production
Immune	Involvement in innate immunity: • S. epidermidis secretes lipopeptides that enhance keratinocyte expression of antimicrobial peptides, including psoriasin (S100A7)
	Involvement in innate immunity: • S. epidermidis activates IL-1–dependent signaling pathways and CD8+cells • Commensal microorganisms secrete lipoteichoic acid, inducing mast cell production of cathelicidin
	Formation of tolerance toward commensal microorganisms: • S. epidermidis promotes formation and accumulation of S. epidermidis –specific regulatory T cells
Physical	Binding to aryl hydrocarbon receptors (transcription factors), stimulating keratinocyte proliferation and differentiation
	Microbial enzymes participate in ceramide synthesis, which reduces transepidermal water loss
	Production of antioxidants: • P/C. acnes produces ROXp protein with potent antioxidant activity, providing protection against oxidative stress • S. epidermidis secretes 6-N-hydroxyaminopurine (6-HAP), which protects against ultraviolet-induced carcinogenesis

 

SKIN MICROBIOTA: VARIABILITY, STABILITY, AND AGE-RELATED FEATURES

Each individual harbors a distinct microbial community, often referred to as the individual microbiome signature, which develops under the influence of a combination of exogenous and endogenous factors, including demographic, physiological variables, and specific lifestyle and dietary habits [30, 31]. An individual’s microbiota is characterized by both variability in response to external and internal influences [30, 31] and stability, reflecting the capacity to maintain its composition over months or years [32]. For instance, studies of skin microbiome variation using 16S rRNA gene sequencing have shown that variations are more pronounced in skin sites exposed to environmental factors such as humidity, temperature, and ultraviolet (UV) radiation [30]. Over the long term, in the absence of significant skin damage or perturbations to the microbiota, the microbial community composition remains stable according to the characteristics of different skin niches and preserves the individual’s microbiome signature [32]. Analyses of microbial strains and single-nucleotide variants indicate that individuals restore and maintain, rather than reacquire, core microorganisms [32].

The human skin microbiome develops early in life and undergoes modification throughout an individual’s lifespan. A particular topic of interest in recent years has been the sterility of the fetal environment and the possibility of in utero microbiome transmission, which has been debated for nearly 150 years [33]. In the second half of the 20th century, experts concluded that the fetus is sterile and exists in a sterile environment [34]. This concept, known as the “sterile womb” paradigm [35], holds that microorganisms are acquired during and after birth—vertically (from the mother) and horizontally (from other individuals or the environment). Recent studies using advanced microbiota research methods have challenged this traditional view. Some authors propose that neither the fetus, placenta, nor amniotic fluid are sterile, and that colonization of the human gastrointestinal tract may begin in utero [36–39]. However, this concept is not universally accepted, and many researchers dispute the presence of an established microbial community in the placenta [40, 41]. Regardless, the maternal gut microbiota plays a critical role in fetal development, with major regulatory effects mediated by metabolites and signaling molecules that penetrate the placental barrier [42]. Consequently, oral administration of probiotics and synbiotics during pregnancy is considered a potential strategy to reduce the risk of certain postnatal diseases [43]. Several clinical studies have demonstrated a reduced incidence of atopic dermatitis (AD) in children aged 0–2 years whose mothers received Lactobacillus rhamnosus probiotics during pregnancy [44]. It should be noted, however, that this protective effect has not been consistently observed across all studies or for every Lactobacillus species [45], highlighting the need for further research.

Currently, it is most commonly postulated that skin colonization by microorganisms occurs after birth [46, 47]. In the first six weeks of life, colonization depends not on the skin niche but on the mode of delivery [48]. Infants delivered vaginally are dominated by Lactobacillus and Prevotella on the skin, whereas infants delivered via cesarean section are dominated by Staphylococcus, Corynebacterium, and Cutibacterium. The high prevalence of AD, inflammatory bowel diseases, obesity, and immune dysregulation in children delivered by cesarean section may be partly mediated by characteristics of the skin and gut microbiota [48]. In this context, the maternal skin microbiota may be critical. Maternal skin dysbiosis, such as that associated with AD, increases the likelihood of transferring opportunistic flora to the newborn and the subsequent risk of allergic dermatoses.

 

The establishment of the skin microbiota by niches occurs only by the third month of life [49], with the first year considered the most critical for the development of both the skin and gut microbiota. Its composition is influenced by feeding practices, child care routines, and maternal lifestyle factors [50]. Subsequent skin colonization by the microbiota continues, with adaptation to exogenous and endogenous factors, and the formation of an individual microbiome signature, which reaches an equilibrium in adulthood [51, 52]. Significant modifications of the skin microbial community occur during puberty, with an increase in the abundance of C. acnes and S. epidermidis in the corresponding niches. In females, the relative abundance of C. acnes and Malassezia restricta correlates with certain hormones, including estrone, 17β-estradiol, and testosterone. Simultaneously, the proportion of Streptococcus decreases [53]. For example, on cheek skin, Streptococcus dominates at ages 0–3 and 7–10 years, S. epidermidis at 13–18 years, and C. acnes at 20–25 years [54]. After 50–55 years, the skin microbiota undergoes further significant changes, and interindividual variability becomes more pronounced. The most notable shifts include increases in Proteobacteria and the relative abundance of Corynebacterium, with decreases in Actinobacteria and Propionibacterium [55–57]. Fungal composition also undergoes age-related changes, with Malassezia sympodialis becoming predominant in older adults [31]. The prevalence of Demodex spp. also increases with age. Reduced sebum production may decrease nutrient availability for commensal bacteria and favor colonization by opportunistic microorganisms.

Overall, an age-related increase in skin microbial diversity at the species level has been reported in multiple studies across different ethnic groups [55, 58, 59]. Skin microbiota composition correlates with morphofunctional changes, particularly the quantity and quality of collagen [60]. Researchers have identified correlations between collagen fiber characteristics and the abundance of specific S. epidermidis strains, which are known nosocomial pathogens and have been found on the skin of individuals in long-term care facilities [61]. These findings support the notion that skin microbiota composition may serve as a biomarker of aging with higher accuracy than the composition of the gut or oral microbiota [62]. Although the functional significance of age-related changes in skin microbiota and their impact on skin aging are not fully understood, studies show that topical application of a cream containing inactivated Lactobacillus plantarum GMNL6 partially restores skin microbiota, with improvements in skin texture, hydration, pigmentation, and erythema [63].

Age-related changes in skin microbiota are also of particular interest in the context of skin carcinogenesis associated with aging and photodamage [22, 64]. For example, microbial composition in areas affected by actinic keratosis and cutaneous squamous cell carcinoma is characterized by increased total bacterial load and elevated relative and absolute abundance of S. aureus [65]. Toxins produced by this microorganism are thought to contribute to DNA damage and enhance UV-induced inflammation, potentiating its carcinogenic effects [66]. Consequently, eradication of S. aureus from actinic keratosis lesions and restoration of the skin microbiota have been proposed as potential strategies to prevent progression to cutaneous squamous cell carcinoma [64]. Supporting this, topical application of an ointment containing Lactobacillus reuteri has been shown to reduce UV-induced inflammation in ex vivo skin models, suppress IL-6 and IL-8 secretion, and exert antimicrobial activity against S. aureus and other pathogenic strains [67].

Skin Microbiota in Sensitive Skin Syndrome

Sensitive skin syndrome is defined as a condition characterized by unpleasant sensations—burning, stinging, itching, or tightness—in response to stimuli that normally should not provoke such reactions (for example, contact with water, exposure to heat or cold, or ordinary physical or chemical factors) [68]. Diagnostic criteria for sensitive skin have not been established, and skin sensitivity is considered a subjective concept [69]. On examination, only minor clinical manifestations may be observed, such as dryness, mild erythema, or skin thinning [70]. The pathogenesis of increased skin sensitivity remains unclear. Enhanced neurosensory and immune responses, combined with impaired skin barrier function, may contribute to the development of the syndrome [71, 72]. Studies of the microbial community composition using 16S rRNA sequencing and ITS1 analysis have demonstrated specific differences in the microbial composition of sensitive skin [73]. These include a more heterogeneous fungal composition and an increased relative abundance of Lactobacillus, whereas the proportions of Cutibacterium and Staphylococcus remain normal. It has been proposed that the increased population of lactic acid–producing Lactobacillus species may underlie skin hyperreactivity in response to lactic acid application [74]. At the same time, topical application of lysates from the probiotic strain Bifidobacterium longum reuter has been shown to reduce vasodilation, edema, mast cell degranulation, tumor necrosis factor-alpha secretion, and transepidermal water loss [75]. Furthermore, lysates of Lacticaseibacillus rhamnosus GG and B. longum increase the expression of tight junction proteins in vitro [76], providing a rationale for their use in managing sensitive skin syndrome.

Skin Microbiota in Dermatoses: the Example of Atopic Dermatitis

Many chronic dermatoses are characterized by alterations in skin microbiota, or dysbiosis [77]. To date, the significance of skin dysbiosis, often associated with a disrupted balance of commensal microorganisms, has been demonstrated in acne [15], seborrheic dermatitis [78], rosacea [16], psoriasis and psoriatic arthritis [79], and alopecia areata [80]. One of the dermatoses that has attracted particular research interest in terms of investigating alterations in the skin microbial community and the potential for their correction is AD.

AD is one of the most common skin diseases [81, 82], and its prevalence continues to rise worldwide [83]. The pathogenesis of AD is complex: it develops in genetically predisposed individuals and is characterized by epidermal barrier dysfunction and immune dysregulation [84, 85]. Equally important in the pathogenesis of AD are disturbances in the skin microbial balance [86]. The skin microbiota in patients with AD is characterized by reduced bacterial diversity, including decreased abundance of commensal genera such as Streptococcus, Corynebacterium, Cutibacterium, and of the phylum Proteobacteria, along with an increased presence of Staphylococcus, primarily S. aureus [87].

Interestingly, quantitative and qualitative changes in the skin microbiota may occur even before the clinical manifestation of AD [88]. It is assumed that staphylococcal commensals of the normal microbiota can modulate skin resistance and help prevent AD exacerbations [89]. Furthermore, treatment with topical corticosteroids, calcineurin inhibitors, or emollients—by restoring the skin barrier function—contributes to normalization of the skin microbial composition [90].

The main marker of skin microbial imbalance in AD is skin colonization by S. aureus. This microorganism is detected on lesional skin in approximately 70% of patients and on non-lesional skin in about 30%. The abundance of S. aureus correlates with disease severity, may serve as a predictor of disease course, and is considered one of the triggers of exacerbations [91, 92]. Adhesion of S. aureus to atopic skin is facilitated by decreased production of antimicrobial peptides (cathelicidin and β-defensin), increased skin pH, and reduced levels of filaggrin and its metabolites [87]. In turn, S. aureus exerts multiple proinflammatory effects, further impairing epidermal barrier function and maintaining immune inflammation in AD.

The use of topical prebiotics and probiotics as part of combination therapy for AD may have beneficial effects on disease activity and reduce S. aureus colonization [93–95]. However, the potential steroid-sparing effects of such formulations, and their compensatory influence on the skin microbiome in patients receiving long-term treatment with topical corticosteroids and calcineurin inhibitors, remain to be clarified.

BACTERIOTHERAPY: MAIN APPROACHES

Understanding the contribution of skin dysbiosis to aging, increased sensitivity, and the pathogenesis of chronic dermatoses has provided the basis for developing strategies aimed at correcting skin microbiota (see Table 2) [18].

 

Table 2. Main approaches in bacteriotherapy

Therapeutic approach	Microbial agent	Effect
Allogeneic flora transplantation  from healthy donors	Roseomonas mucosa	• Reduced severity of AD • Steroid-sparing effect • Decreased S. aureus abundance • Improved skin condition in children and adults without adverse events
	CoNS strains with antimicrobial activity	• Reduced S. aureus abundance on lesional skin in AD patients • Decreased disease severity at application sites • Improved skin condition in children and adults without adverse events
Autologous bacterial transplants (Staphylococcus epidermidis, Staphylococcus hominis)	Repeated application of antimicrobial S. epidermidis or S. hominis strains	• Reduced S. aureus colonization density in patients with AD
	Topical S. hominis A9	• Suppressed S. aureus toxin production • Did not significantly improve disease severity
Topical cosmetic formulations containing inactivated bacteria or their fragments, or bacterially derived substances (metabiotics)	Lactobacillus plantarum LB244R и LB356R	• Strong activity against S. aureus
	Inactivated Lactobacillus jonsonii NCC 533	• Reduced S. aureus colonization • Anti-inflammatory effect (SCORAD index)
	Inactivated Lactobacillus reuteri	• No significant effects
	I-modulia (Aquaphilius dolomiae extract)	• Reduced S. aureus colonization • Anti-inflammatory effect • Anti-pruritic effect
	Vitreoscilla filiformis extract	• Reduced S. aureus colonization • Anti-inflammatory effect (EASI index)

Note: AD, atopic dermatitis; CoNS, coagulase-negative staphylococci; EASI, Eczema Area and Severity Index; SCORAD, SCORing Atopic Dermatitis clinical tool.

 

The use of antibacterial agents helps suppress the activity of pathogenic microorganisms and create conditions for restoring the population and function of commensal species. For example, antibiotic therapy in AD is associated with a reduction in the relative abundance of S. aureus, increased microbial diversity, and clinical improvement of the skin condition [96]. However, long-term use of antibiotics for the treatment and prevention of skin diseases is not advisable, as it may suppress commensal activity and promote the development of antimicrobial resistance [97].

Another strategy focuses on normalizing skin microbial composition through the use of live bacteria [17]. This approach is implemented either by colonization of the skin with commensals or through the production of antimicrobial peptides and other metabolites that inhibit the growth of pathogenic flora by host cells stimulated by transplanted bacteria [17]. For instance, in AD, autologous bacterial transplants of S. epidermidis or Staphylococcus hominis, and allogeneic bacterial transplants of coagulase-negative staphylococci (CoNS) or Roseomonas mucosa, have been used. Bacteriotherapy with live bacteria in patients with AD has been shown to reduce disease activity and S. aureus colonization of the skin.

Finally, stimulation of commensal or host cell activity can be induced by inactivated microorganisms, components of their cell walls, bacteriocins, short-chain fatty acids, signaling molecules, and metabolites of the normal flora [17, 19, 20, 98]. Inactivated bacteria, their fragments, or lysates are incorporated into topical formulations, including dermocosmetic products [17, 20, 98].

Among bacteria considered as potential sources of active ingredients for dermatocosmetic products, lactic acid bacteria deserve particular attention. These bacteria are components of the normal gut microbiota, producers of antimicrobial compounds such as organic acids and bacteriocins, and widely used as probiotics and sources of metabiotics [99]. In a comparative study of the antibacterial activity of various Lactobacillus strains in patients with AD, L. plantarum strains LB244R and LB356R exhibited the strongest inhibitory effect against S. aureus [99]. Notably, inactivated L. plantarum or components of their cell walls have demonstrated high clinical efficacy in topical formulations for the treatment of third-degree burns [100] and chronic infected lower-extremity ulcers in patients with diabetes mellitus [100–102]. These applications were associated with reduced bacterial load, decreased numbers of biofilm-producing bacteria, accelerated granulation tissue formation, and enhanced wound healing.

Biotic Complexes in Dermatocosmetic Products

For several decades, microbial lysates have been used as sources of active metabolites and signaling molecules (short-chain acids, bacteriocins, polysaccharides, and peptides), and structural components (e.g., cell wall fragments) responsible for in vitro and in vivo effects. These lysates are essentially metabiotics [103, 104]. The term metabiotic contains the Greek prefix meta- (change, transformation), reflecting its ability to initiate a wide range of neurochemical processes [105]. Currently, metabiotics containing low-molecular-weight bacterial compounds are used not only as pharmaceuticals or dietary supplements for restoring gut microbiota but also in topical formulations. Their widespread use is due to their safety, stability, long shelf life, and ease of dosing [103, 104]. The effects of metabiotics are mediated by their capacity to enhance specific host physiological functions, including regulatory and metabolic processes, and are closely associated with host microbiota activity [106].

Thus, topical application of probiotic metabiotics, especially within biotic complexes, appears promising for the treatment of dermatoses, including AD, for counteracting age-related skin changes, and for daily skin care. Components of biotic complexes may exert pathogenetically relevant effects in these contexts and are considered safe.

LE SANTI® MICROBIOME SKINCARE SERIES

A practical implementation of probiotic-based metabiotics within biotic complexes is LE SANTI® MICROBIOME SKINCARE series (Russia). All products contain the LE SANTI® biotic complex, which includes lysates of probiotic microorganisms (Lactococcus, Lactobacillus and Bifidobacterium) and prebiotics (trehalose and inulin). The activity of each product is enhanced by additional ingredients with proven efficacy, such as panthenol, jojoba oil, shea butter, and others.

Evidence Base

The enhanced biotic complex formulation, consisting of lysates of three probiotic microorganisms and prebiotics, supports normalization of the skin microbiome, suppresses pathogenic flora, and promotes the growth of beneficial microorganisms, which is important for maintaining skin health and barrier function.

The synergy between probiotics and prebiotics improves the overall effectiveness of the system, including skincare products based on it.

Clinical studies have confirmed the efficacy of the enhanced BIOTIC COMPLEX³ formula in patients with AD. In a study evaluating the efficacy and safety of a cream containing shea butter, squalane, vitamin E, ceramides, and sodium hyaluronate, and its effects on biomechanical skin parameters in children with AD, the cream was shown to positively influence the skin condition, promoting regression of lesions and relief of subjective symptoms (itching, burning), and restoring the epidermal barrier [111–115].

In a prospective observational program, 25 children aged 3–17 years (mean age 9.2 years) applied the cream twice daily (at 9.00 a.m. and 7.00 p.m.) for 28 days. AD progression was assessed using the SCORAD (SCORing Atopic Dermatitis) index, the Dermatology Life Quality Index (DLQI), and measurements of tewametry, corneometry, and sebumetry. At the end of the study, the mean SCORAD score decreased 1.9-fold (from 26.2 to 14.0), and the mean DLQI score decreased more than 3-fold (from 12.1 to 3.5). Clinical effects were associated with improvements in skin morphofunctional parameters, including hydration, sebum content, and pH. Skin hydration increased 3-fold (from 12.3 AU at baseline to 37.6 AU at study end), sebum content increased more than 3.5-fold (from 0.9 AU to 3.3 AU), pH shifted toward acidic values (from 6.5 to 5.5), and skin elasticity increased by 30% (from 64.9 to 87.4). Safety was confirmed, as no adverse events related to cream use were reported among participants.

DISCUSSION

The relevance and efficacy of emollients containing biotic complexes for daily skin care, and for use in combination therapy of dermatoses and conditions associated with skin microbiota dysbiosis, are beyond doubt. The use of such products opens a field of potential therapeutic opportunities for patients with skin diseases associated with dysbiosis and impaired skin barrier function. Bacteriotherapy of dermatoses using topical formulations containing biotic complexes is actively developing. The ingredients in these products can complement traditional emollient components, and the combination of prebiotics and probiotics leads to synergistic effects and enhanced system efficacy. At the same time, it is important to emphasize the need for further clinical studies on the effects of emollients containing biotic complexes and the expansion of the evidence base for their efficacy.

The use of LE SANTI® MICROBIOME SKINCARE in patients with AD, including children and pregnant women, and in sensitive skin syndrome and age-related skin changes, has substantial scientific and practical rationale. Clinical studies evaluating the efficacy and safety of the entire product series in patients with AD have demonstrated the clinical effectiveness of these emollients, their pathogenetically relevant effects on restoring skin pH and parameters reflecting skin barrier function, and normalization of the skin microbial community.

CONCLUSION

The main effects of the enhanced formula product series are mediated by the biologically active and signaling molecules, which modulate skin functions, including regulatory and metabolic processes, and are closely related to the activity of the human microbiota.

Microbial lysates serve as sources of active metabolites and signaling molecules (short-chain acids, bacteriocins, polysaccharides, and peptides), and structural components (e.g., bacterial cell wall fragments), which exert complex physiological effects when included in topical emollients. Their widespread use is due to safety, stability, long shelf life, and ease of dosing.

Ingredients in the innovative formula (lysates of probiotic microorganisms and prebiotics) potentiate each other’s effects.

Studies have demonstrated the efficacy and safety of the enhanced formula series in the context of combination therapy for patients with AD. The observed clinical effects are based on restoration of the skin barrier (as measured by pH values, transepidermal water loss, and skin elasticity) and normalization of the skin microbial composition (reduced prevalence of phyla considered opportunistic pathogenic and decreased abundance of the Staphylococcaceae family, whose pathogenic members contribute to inflammation and allergic skin reactions).

The application of this enhanced formula series appears promising for skin care in pregnant women, including those with AD, women planning cesarean delivery, patients with sensitive skin syndrome, age-related skin involution, photodamage, and in systemic diseases associated with skin dysbiosis (e.g., diabetes mellitus).

Further studies are warranted to evaluate the efficacy and safety of this product line in various conditions and dermatoses characterized by skin dysbiosis.

Increasing physician awareness regarding the use of enhanced formula products as part of comprehensive therapy for AD and other dermatoses is recommended. Educational programs should be developed for dermatovenereologists and related specialists involved in the management of patients with skin dysbiosis.

ADDITIONAL INFORMATION

Author contributions. I.O. Smirnova, V.P. Adaskevich, D.V. Zaslavsky, O.B. Tamrazova, I.L. Shlivko ― concept development, reviewing, approval of the final version of the article; A.N. Gorodovich, V.A. Okhlopkov, A.V. Taganov, K.D. Khazhomiya ― systematization of information, collection and analysis of literary sources, editing of the article. Thereby, all authors provided approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding sources. The article was prepared with external funding with the participation of Vertex LLC.

Disclosure of interests. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Statement of originality. The authors did not utilize previously published information (text, illustrations, data) in conducting the research and creating this paper.

Data availability statement. Access to the data obtained in this study is not provided.

Generative AI. Generative AI technologies were not used for this article creation.

Provenance and peer-review. This paper was submitted to the journal on an initiative basis and reviewed according to the usual procedure. Two external reviewers and the scientific editor of the publication participated in the review.

About the authors

Vladimir P. Adaskevich

Vitebsk State Order of Peoples' Friendship Medical University

Email: Vitebsk-derma@mail.ru
ORCID iD: 0000-0002-5700-9829
SPIN-code: 3721-9080

MD, Dr. Sci. (Medicine), Professor

Belarus, Vitebsk

Aleksei N. Gorodovich

Polotsk Central City Hospital

Email: polotsk.mod@gmail.com
Belarus, Polotsk

Denis V. Zaslavsky

Saint-Petersburg State Pediatric Medical University

Email: venerology@gmail.com
ORCID iD: 0000-0001-5936-6232
SPIN-code: 5832-9510

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

Vitaly A. Okhlopkov

Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology

Email: vokhlopkov@fnkcrr.ru
ORCID iD: 0000-0002-3515-6027
SPIN-code: 1202-6653

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Solnechnogorsk, Lytkino village

Irina O. Smirnova

Saint-Petersburg State University; City Skin and Venereological Dispensary

Email: driosmirnova@yandex.ru
ORCID iD: 0000-0001-8584-615X
SPIN-code: 5518-6453

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg; 3 Volkovka river embankment, Saint Petersburg, 192102

Alexey V. Taganov

Pierre Wolkenstein Clinic of Skin Diseases

Email: matis87177@yandex.ru
ORCID iD: 0000-0001-5056-374X
SPIN-code: 1191-8991

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Olga B. Tamrazova

Peoples' Friendship University of Russia

Email: anait_tamrazova@mail.ru
ORCID iD: 0000-0003-3261-6718
SPIN-code: 5476-8497

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Irena L. Shlivko

Privolzhsky Research Medical University

Email: irshlivko@gmail.com
ORCID iD: 0000-0001-7253-7091
SPIN-code: 8301-4815

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Nizhny Novgorod

Kristina D. Khazhomiya

City Skin and Venereological Dispensary

Author for correspondence.
Email: christinakhazhomiya@gmail.com
ORCID iD: 0000-0002-2997-6109
SPIN-code: 2796-4870
Russian Federation, 3 Volkovka river embankment, Saint Petersburg, 192102

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