2. Prebiotics, Probiotics and Postbiotics
Prebiotics are specific fermented substances or dietary supplements that are not digested, enhancing intestinal health by encouraging the growth of commensal bacteria
[50]. On the other hand, probiotics are non-pathogenic live microorganisms, frequently yeast or bacteria, that, when administered in sufficient amounts, confer a health benefit to the host
[51][52][51,52]. Probiotics from the first generation are commonly available products to treat microecological disorders. The next level of development is the production of “metabiotics”, which are small molecules or chemicals obtained from probiotic microorganisms. The bioactive compounds produced by symbiotic microorganisms (a combination of probiotics and prebiotics) from naturally occurring probiotic strains, or natural sources can be used to synthesize or semi-synthesize these metabiotics. They are known as “metabolic probiotics”, “postbiotics”, “biological drugs”, or “pharmacobiotics”. These compounds have the potential to impact the microbiota, human metabolic processes, signaling pathways, and physiological activities related to the host. Postbiotics have recognized chemical structures that may improve the composition and functionality of the host’s native microbiota as well as components involved in immunology, neurohormone biology, and metabolic and behavioral responses
[53]. For instance, many commensal bacteria produce butyrate, a postbiotic that is a major source of energy for the colon and is essential for intestinal growth, differentiation, and inflammation control
[54][55][54,55]. Moreover, postbiotics are probiotic-derived effector chemicals secreted by bacteria or released after lysis and capable of exerting qualities identical to those of the original probiotics
[56][57][56,57] (
Figure 2). They attempt to imitate the benefits of probiotics without taking the risk of administering live bacteria. While these probiotics, prebiotics, and postbiotics are commonly associated with dietary supplements targeting the gut microbiome, their application extends beyond the digestive system to various body parts, including the skin. In dermatology, particularly in addressing skin conditions, these concepts find relevance as researchers explore their potential in topical formulations and skincare products.
Figure 2.
Prebiotics, Probiotics, and Postbiotics. Created with
.
3. Skin Microbiome
The connection between microbial communities and the host tissue is symbiotic in the skin. The importance of resident microbial communities in maintaining the skin’s and immune system’s normal, healthy function has been demonstrated recently
[58][59][58,59]. A diverse group of microorganisms known as the skin microbiome work together to maintain a complicated connection on the skin
[1]. A large and diverse community of bacteria, viruses, and eukaryotes, including fungi and arthropods, comprise the human skin microbiota
[60][61][60,61]. The heterogeneity of the skin microbiota, both in terms of its composition and prevalence, can be demonstrated in the significant variances between individuals and between different skin regions. These differences can be attributable to a complex interaction of elements, including genetic predisposition, dietary habits, choice of lifestyle, gender, age, ethnic background, and environmental circumstances
[62][63][62,63]. The skin provides essential nutrients to establish its microbiota, including amino acids, fatty acids, and lactic acids from various sources like proteins, the stratum corneum, sweat, lipid hydrolysis, and sebum
[64]. This relationship between the host and commensal microorganisms is vital for various physiological processes. To maintain this symbiotic relationship, commensal-specific T cells play a role in distinguishing between resident microorganisms and potential pathogens, thereby promoting tolerance towards the commensal microbiota
[65]. The skin microbiome is made up of several different bacterial species. Microorganism imbalances can lead to skin diseases such as acne, AD, psoriasis, and rosacea
[66]. Probiotic bacteria have been used to make a variety of treatments, nutritional items, and additives that support human health
[67]. They provide several functions, one of which is serving as the first line of defense against invasive diseases and are also used to prevent both acute and chronic disorders or prophylaxis
[68]. This shows that probiotics are used as an avoidance strategy for some disorders. In addition, specific health conditions, such as acute or chronic diarrhea and intestinal inflammation that can cause allergies, atherosclerosis, and cancer, are also treated with probiotic medications
[69]. Coagulation-negative Staphylococci are also prevalent on human skin, and they act via a number of mechanisms including the epidermal barrier environment and the innate and adaptive immune systems found in the epidermis and dermis
[70]. Further, the bacteriocins produced by this species have anti-inflammatory, and antibacterial characteristics that reduce the survival of harmful bacteria on the skin surface
[41]. Endogenous urocanic acid found in the stratum corneum of the skin acts similarly to sunscreens in preventing damaging Ultraviolet (UV) radiation from penetrating the epidermis
[67][71][67,71].
The microorganisms that make up the skin microbiome cooperate to keep the skin safe. However, due to many factors, such as external ones, commensal microorganisms may transform into pathogenic microbes, causing inflammation, itching, scaling, and other medical symptoms that point to an imbalance between our skin and its microbiome
[72]. The word “dysbiosis” is used to describe how the microbiome of the skin has changed. Functional dysbiosis disturbs the interactions between bacteria and hosts and causes skin issues. Age, sex, hygiene, the use of particular pharmaceuticals, skin pH, sweating propensity, hair development on the skin, sebum production, usage of skin cosmetics, and lifestyle are only a few of the host factors that have an impact on the microbiome host interaction
[73]. The potential of oral probiotics as a treatment for skin conditions has increased as research has revealed a connection between disrupted gut microbiota and inflammatory skin conditions
[74]. Researchers are actively investigating the relationships among changes in the gut microbiota, immune system dysregulation, and the development or aggravation of autoimmune skin disorders, aiming to identify biomarkers and molecular pathways for potential therapeutic targeting
[75][76][77][75,76,77]. Studies on probiotics have been performed using a concept known as the gut–brain–skin axis idea. These studies have demonstrated the efficacy of probiotics in the management of some dermatological conditions, including psoriasis, acne, vitiligo, and AD
[2][78][2,78]. For example, AD is characterized by cutaneous dysbiosis and a greater presence of
Staphylococci like
S. aureus and
Malassezia spp. These microorganisms release toxic chemicals and nanovesicles that trigger cytokines, which contribute to the persistence and aggravation of AD symptoms.
Transplanting specific strains of
S. epidermidis and
S. hominis that produce antimicrobial peptides resulted in significant decreases in the levels of
S. aureus in individuals with AD. This implies a promising therapeutic strategy for addressing AD by influencing the skin’s microbiome to regulate and reduce the overgrowth of
S. aureus [79]. The local skin microbiome plays a role in psoriasis pathogens. Psoriasis patients have a similar major species of bacteria in their skin flora compared to non-psoriasis individuals but with reduced diversity and changes in the relative abundance of certain bacteria. Specifically, lower concentrations of
Cutibacterium acnes (formerly
Propionibacterium) and
Actinobacteria species are found in psoriasis patients, while higher concentrations of
Firmicutes,
Proteobacteria,
Acidobacteria,
Schlegelella,
Streptococcaceae,
Rhodobacteraceae,
Campylobacteraceae, and
Moraxellaceae species are observed when compared to controls. This suggests that alterations in the skin microbiome may contribute to psoriasis alongside immune system dysfunction
[80][81][80,81]. As a result, these skin disorders present greater opportunities for probiotic research regarding topical benefits. In general, the gut microbiota is responsible for the body’s appropriate immunity and defense against harmful microbes. Therefore, alterations that are considered harmful at the intestinal microbiota level may result in infections and autoimmune diseases in a variety of organs outside of the colon, including the skin
[82]. A recent study
[83] shows that patients with vitiligo have a different microbial composition from healthy people, with a considerably lower Bacteroidetes to Firmicutes ratio. They also differ significantly from healthy people in 23 blood metabolites, and these metabolites are linked to particular microbial indicators. Commensal bacteria are vital components of the skin microbiome and play a crucial role in skin health. Another study
[84] highlights that vitiligo-affected skin exhibits a dysbiosis in microbial community diversity, with lesional areas showing reduced taxonomic richness and evenness. Notably, Actinobacterial species are dominant in normal skin, while Firmicutes species dominate in vitiligo lesions, suggesting that these microbial changes could influence the development and severity of vitiligo.
4. Mechanisms of Action for Topical Prebiotics, Postbiotics and Probiotics
Many low-molecular-weight (LMW) bioactive substances, such as bacteriocins and other antimicrobial compounds, short-chain fatty acids, various fatty and organic acids, biosurfactants, polysaccharides, peptidoglycans, teichoic acids, lipo- and glycoproteins, vitamins, antioxidants, nucleic acids, amino acids, and different proteins, including enzymes and lectins, can be derived from different probiotic strains
[85][86][85,86]. The applicable agents of these groups of LMW compounds isolated from symbiotic microorganisms or their cultural liquids may be used to produce functional foods, drugs for the prophylaxis and treatment of chronic human diseases, as well as sports and anti-aging foods
[87][88][87,88]. The application of the probiotics concept in biotechnology has made it possible to include several thousand additional strains from the human-dominant intestinal phyla (Bacteroides, Firmicutes, Proteobacteria, Actinobacteria, and Archae) for nutritional and therapeutic purposes in addition to
Bifidobacteria,
Lactobacilli,
Escherichia, and
Enterococci sp.
[89][90][89,90].
Microbiome development and changes are influenced by various factors such as childbirth, diet, drugs, and diseases
[91]. The skin microbiota varies significantly across different body regions due to the presence of unique glands and hair follicles, creating distinct conditions for microbial growth. Specific bacterial and fungal species dominate various areas, such as lipophilic bacteria in sebaceous regions and fungal communities on the feet. Additionally, the facial skin microbiota is mainly composed of Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes, with variations linked to age, and diversity differs by facial location, with cheek sites having the highest richness scores. Postbiotics like acetate, propionate, and butyrate play a crucial role in intestinal health by providing energy, enhancing the epithelial barrier, regulating immunity, and preventing pathogen invasion
[92]. Immune diseases, inflammation, and gut dysbiosis can result from a dysregulation of this balance
[93]. The gut–skin axis is proposed as a connection between emotional states, gut health, and skin conditions. Increased intestinal permeability can activate T cells, disrupt immunosuppressive factors, and lead to systemic inflammation, potentially affecting skin homeostasis
[94]. Gut microbes can also communicate with other organs through neurotransmitter production. Therefore, changes in the gut microbiome may directly impact systemic inflammation
[92]. In the last century, the ability to identify microorganisms based on their appearance or biochemical traits and improvements in cell culture techniques have allowed for the expansion of study into the microbial variety of human skin. Researchers have identified numerous genera of bacteria that are typically found on healthy skin using culture-dependent methods. These genera include
Staphylococci,
Micrococci,
Corynebacteria,
Brevibacteria,
Propionibacteria, and
Acinetobacter [95].
Staphylococcus aureus,
Streptococcus pyogenes, and
Pseudomonas aeruginosa were identified at the species level using culture techniques, such as colonizers in unusual conditions
[96]. The skin microbiome is primarily made up of two main types of bacteria: the resident and transient microbiota types. The resident microbiota is the most significant and persistent group and may regenerate after any disturbances
[97]. In contrast, the transitory microbiome is environment-dependent and only stays on the skin for a few hours or days
[98]. Both of these microbiota types are harmless in healthy skin. Actinobacteria, Firmicutes, Proteobacteria, and Bacteroides are some of the most prevalent phyla on the skin, while the most common genera are
Corynebacterium,
Propionibacterium, and
Staphylococci [66][99][66,99].
5. Clinical Verification and Effectiveness
The effectiveness of probiotic products used topically has received very little investigation. However, in the past ten years, the number of commercially available topical probiotics has dramatically increased
[100], and probiotics have been applied topically and orally to treat various skin disorders
[53] Table 1. The gut microbiota significantly affects the immune system, and many studies
[2][101][102][2,101,102] have shown the importance of dysregulations in the skin and gut microbiome in immune-related diseases. Immune dysregulation driven by imbalances in the gut microbiota may involve an excessive immune response that targets melanocytes and contributes to their destruction in vitiligo
[103]. It is thought that both genetic and environmental factors play a role in the vitiligo development process. Recent research indicates that vitiligo patients have altered immune responses and increased stress-induced production of Interferon-gamma (IFN-γ), which leads to melanocyte apoptosis
[104]. Dysbiosis in the gut microbiome is observed in vitiligo patients, with reduced Bacteroides populations and changes in microbiota diversity, which are associated with mitochondrial damage and peripheral changes in innate immunity
[105]. Skin microbiota composition also differs between vitiligo patients and healthy controls, particularly in vitiligo lesions, where there is a reduction in
Staphylococcus and
Cutibacterium and an increase in
Proteobacteria associated with inflammation
[103].
Table 1.
Examples of Probiotic-Containing Commercial Products.
The topical application of probiotic bacteria may help enhance the skin’s natural barrier by directly affecting the site of application. This may be performed by the resident bacteria and the probiotic bacteria that produce certain antimicrobial amino peptides that benefit the immune responses in the skin and help eliminate pathogens
[106]. The administration of probiotic species that are not native to a particular ecosystem can potentially cause adverse effects
[107]. They are commonly included in over-the-counter cosmeceutical products, but their effectiveness may be compromised by their high bacterial load and the preservatives used, which can impact the skin’s microbiota
[108]. Probiotics have been utilized in a variety of cosmetic items, including lotions, intimate hygiene products, shampoos, and toothpaste. These strains include
Bacillus subtilis,
Lactobacillus acidophilus,
Lactobacillus casei, and
Lactobacillus plantarum. These probiotics provide several benefits for skin health, including moisturizing effects, reducing toxic metabolites, enhancing antibody production, restoring immune system balance, and regulating cytokine synthesis
[109][110][109,110]. In addition, topically applied probiotics can serve as a protective barrier on the skin by competing with and inhibiting the binding of potential pathogens to skin sites. This competitive inhibition helps prevent the colonization of harmful microorganisms on the skin, further contributing to skin health and protection
[100].
Postbiotics, formed from microbial growth by-products or inactive dead strains, positively benefit skin health because they contain bioactive substances such as bacteriocins, lipoteichoic acids, and organic acids
[111]. Species of
Lactobacillus, including those found in cosmetics, create lactic acid, which aids in moisturization and anti-aging
[112].
Streptococcus and
Bifidobacterium strains have also been demonstrated to increase skin hydration and elasticity, with
Bifidobacterium contributing to the production of hyaluronic acid for improved skin appearance
[113][114][113,114].
Novel strategies in the field of dermatology employ nanocarriers to improve the topical applications of probiotics and prebiotics
[4][6][4,6]. These nanocarriers, often in the form of nanoparticles or nanoemulsions, serve as efficient vehicles for loading and delivering probiotic strains to the skin. This advanced delivery system not only protects the viability of probiotics during formulation but also enhances their penetration into the skin, maximizing their potential to establish a protective barrier.