The Challenges of Topical Probiotics
Exciting research on how to positively manipulate the skin microbiome to mitigate or alleviate inflammatory skin conditions (conditions resulting from dysbiosis) using topically-applied probiotics is currently underway, but its clinical application is not without challenges of efficacious formulation and delivery.
Ample literature illustrates that oral probiotics can improve inflammatory skin conditions by modulating the gut microbiome (and thus the gut-skin axis), and newer research is highlighting topical probiotics’ ability to directly improve the skin microbiome.¹ As mentioned in previous posts, inflammatory skin conditions result from dysbiosis of the skin microbiome, or an imbalance in the community of microbes living on one’s skin. Overgrowth of certain species and/or loss of abundance of other species of microbes are seen in acne, atopic dermatitis/eczema, rosacea, seborrheic dermatitis/dandruff, and even skin aging.¹ In atopic dermatitis, for example, there is a greater abundance of S. aureus (known for its inflammation-triggering and barrier-disrupting properties), as well as a lower overall skin microbe diversity.¹
The skin microbiome can be influenced by a number of factors: sweat, hormones, stress, climate, age, hygiene, sebum production, lifestyle, cosmetics, and more.² Even air pollution has been shown to negatively affect skin microbiome diversity.³ Different areas of skin (i.e. your scalp versus the soles of your feet) - depending on whether they are sebaceous, dry, or moist - are dominated by different communities of microorganisms, so what is considered “healthy” and optimal in one area of skin might be a sign of imbalance in another area.² When the skin microbiome is out-of-balance (dysbiotic), there is increased inflammatory cytokine production, weakening of the skin barrier (loss of epidermal tight junctions), and immune system dysregulation.
The topical application of various species of probiotics, on the other hand, has been shown to block inflammatory cytokine release (reduce inflammation), strengthen the skin barrier, promote immune tolerance, and even offer UV protection.¹ Nitrosomonas eutropha and Lactobacillus buchneri have shown promise in anti-aging of the skin; Vitreoscilla filiformis, Streptococcus thermophilus, and Lactobacillus johnsonii have been shown to be beneficial for those with atopic dermatitis; Bifidobacterium breve BR03 and Lactobacillus salivarius are implicated in the alleviation of rosacea; Lactiplantibacillus plantarum, kefir. L. fermentum, and Saccharomyces cerevisiae promote wound healing; Lactobacillus paracasei demonstrates potential in treating dandruff; and Streptococcus thermophiles, Enterococcus faecalis, and Streptococcus salivarius reduce acne.¹ With the macroscopic diversity of these microscopic organisms, the potential for clinical application feels endless. The beneficial effects of topical probiotics could be mediated by the modulation of gene expression (genes involved in T-cell signaling, immune regulation, and inflammatory cascades), competitive inhibition of pathogenic bacteria, or the production of microbe-derived metabolites, such as antimicrobial peptides (AMPs).² The discovery and use of AMPs and other microbial metabolic byproducts (bacteriocins, enzymes, organic acids, etc.) has led to a rise in the popularity of “postbiotics” in skincare products, consisting of ferment lysates and filtrates, which are bioactive compounds or components of inanimate microorganisms that can confer benefits to the user. While probiotics consist of living microorganisms, postbiotics contain only a filtrate or lysate (of a ferment), which simplifies the sterilization and preservation of a skincare product containing postbiotics as opposed to probiotics.
Despite growing hope towards the potential clinical application of this research, large hurdles remain regarding effective formulation and delivery of topical probiotics. As scientists anxiously await further results and explore additional experiments, eager marketers are distributing products that might not be as effective as they claim. The novelty of prebiotic, probiotic, and postbiotic skincare makes for an unregulated market that could easily become saturated with misleading claims.
Misleading Advertising in the Current Market
Unlike drugs, cosmetics do not require FDA approval, nor must they adhere to GMP guidelines or register their formulations. The intended use of a product dictates its labeling as either a cosmetic or a drug, which creates a so-called grey area for many products whose claims extend beyond appearance modification. Consumer competence becomes essential when selecting a skincare product, particularly in understanding “trigger” or “trendy” advertising phrases, interpreting misleading claims, and reading long ingredient lists. For instance, unsubstantiated claims of “microbiome restoration” or “microbiome balance” (or some variation of this claim) are seen on numerous cosmetics nowadays, without a clear definition of what constitutes a true benefit to the microbiome. The definitions of “prebiotic” and “postbiotic” also remain unregulated and in flux; many skincare products containing prebiotics or postbiotics are routinely advertised as probiotics (which implies it contains living microorganisms that confer a health benefit). As for products that do contain live “probiotic” organisms, sterilizing preservatives in the product may destroy the probiotics before use; these same preservatives may also negatively impact the user’s skin microbiome upon application.⁴ However, without some form of preservation, live species may grow and multiply, altering the stated CFU count or changing the desired microbial strains, potentially contributing maleficient microorganisms to the user’s skin upon use.⁴
As it is in the supplement and nutrition markets (with their ever-expanding amounts of misinformation and false advertising), it has become up to the consumer to discern between various labels: “grass-fed” may not imply “grass-finished”; “sugar-free” may instead mean the product contains artificial sweeteners (known to cause gut disruption) and/or only non-refined sugar (coconut sugar, maple syrup, honey, agave, etc.); “natural” holds almost no weight considering its unregulated definition; “organic” eggs may or may not have come from 100% pasture-raised chickens; and “good for microbiome” could mean hundreds of different things, ranging from the product’s pH matching that of the facial skin to a product containing a “prebiotic” to a product formulated without preservatives.
The Use of Lyophilization
Despite the overwhelming evidence that live organisms (probiotics) can tremendously benefit the skin (& improve microbiome homeostasis) and improve skin conditions (caused by dysbiosis), it is not as simple as adding live organisms to one’s moisturizer. Formulation and delivery of topical probiotics must be carefully considered to ensure the proper species and strains are applied to the skin, and the skincare product remains viable for long durations under usual user conditions (room temperature, oxygen-exposure, etc.).⁵ Additionally, further research regarding which species and strains are most beneficial for varying conditions and dysbiotic states still needs to be accomplished.
Due to the lack of regulation within the U.S. cosmetic industry (as discussed above), claims regarding CFU counts and live bacteria content may not hold true under testing conditions. Using preservatives to ensure a sterile skincare product may kill live probiotics in the product, or negatively affect the user’s skin microbiome upon application.⁴ Without preservatives, though, unwanted populations may grow. Although some research indicates that in low-water formulations there is no mold or yeast growth after 30 days, bacterial populations still decrease, maintaining the idea that lyophilization is a preferred method of preservation.⁵ Some products use a phosphate buffer system (PBS) that allows the desired bacteria to survive for short durations but inhibits additional bacterial growth.⁵ However, the bacteria in a PBS will not remain viable for long, and often, the product requires either refrigeration and/or a substantial loss of efficacy over the course of a few weeks.
A widely publicized clinical trail involving the safety and efficacy of Roseomonas mucosa in the treatment of atopic dermatitis lyophilized (freeze-dried) the bacteria to ensure long-lasting survivability; the probiotic was then rehydrated immediately prior to application and sprayed onto the skin.⁶ The success of these trials provided further evidence to the mounting research on the survivability of bacterial species following lyophilization. Although lyophilization still has its risks (potential loss of bacterial viability), the CFU count can be maintained at a high enough level that even if a percentage of bacteria did not survive lyophilization and rehydration, there would still be ample bacteria to provide a benefit to the user upon application. My topical probiotics consist of lyophilized species that are only rehydrated and activated upon application to ensure maintenance of a sterile product and preservation of only the desired strains and species.
The challenges associated with topical probiotic formulation and delivery can be easily overcome, but in the meantime, consumers should be aware of misleading information within the cosmetic industry.
References
Habeebuddin M, Karnati RK, Shiroorkar PN, Nagaraja S, Asdaq SMB, Khalid Anwer M, et al. Topical probiotics: More than a skin deep. Pharmaceutics [Internet]. 2022;14(3):557. Available from: http://dx.doi.org/10.3390/pharmaceutics14030557
Boxberger M, Cenizo V, Cassir N, La Scola B. Challenges in exploring and manipulating the human skin microbiome. Microbiome [Internet]. 2021;9(1):125. Available from: http://dx.doi.org/10.1186/s40168-021-01062-5
Leung MHY, Tong X, Bastien P, Guinot F, Tenenhaus A, Appenzeller BMR, et al. Changes of the human skin microbiota upon chronic exposure to polycyclic aromatic hydrocarbon pollutants. Microbiome [Internet]. 2020;8(1):100. Available from: http://dx.doi.org/10.1186/s40168-020-00874-1
Puebla-Barragan S, Reid G. Probiotics in cosmetic and personal care products: Trends and challenges. Molecules [Internet]. 2021;26(5):1249. Available from: http://dx.doi.org/10.3390/molecules26051249
Vargason AM, Anselmo AC. Live biotherapeutic products and probiotics for the skin. Adv Nanobiomed Res [Internet]. 2021;1(12):2100118. Available from: http://dx.doi.org/10.1002/anbr.202100118
Myles IA, Castillo CR, Barbian KD, Kanakabandi K, Virtaneva K, Fitzmeyer E, et al. Therapeutic responses to Roseomonas mucosa in atopic dermatitis may involve lipid-mediated TNF-related epithelial repair. Sci Transl Med [Internet]. 2020 [cited 2023 Mar 8];12(560):eaaz8631. Available from: https://pubmed.ncbi.nlm.nih.gov/32908007/