Probiotics in dermatology: acne as a case study

Acne remains a tragedy for those affected as even after more than a century of extensive study, the condition still remains a serious problem. Can probiotics hold the answers that have eluded dermatologists for so long? The gut–skin axis is showing us that the old adage ‘we are what we eat’ has never been truer. Oral probiotics could influence the gut, so that the gut influences the skin in a way that improves acne.

Topical probiotics are also proving helpful in the fight against acne.  In the paper ‘Skin microbiome transplantation and manipulation: current state of the art’, Bernhard Paetzold, Chief Scientific Officer at S-Biomedic, and co-authors consider the challenges of skin microbiome transplantation and skin bacteriotherapy. They conclude that despite the many challenges involved, such as ensuring that the population of the applied bacteria on the skin remains stable, it is likely that dermatologists will soon be adding topical probiotics to their list of key acne treatments [1].

However, it is still early days for probiotics, with only a limited number of peer-reviewed studies available to support their use for acne.

Similarities between gut and skin may explain how oral probiotics work

My exasperated biology lecturer once described my class as being a lazy group of cellular tubes! Although this description was not at all flattering at the time, fundamentally she was quite correct. Simplistically, our outer epidermal stratum corneum and our inner gut are more or less a continuous surface, much like the surfaces of tubes or doughnuts.

Skin and gut tissue have more in common than you might at first think. Although the primary roles of the gut and skin are obviously very different, together they make up our barrier to the exogenous world. They are both very responsive. Their epithelial cells have receptors, which learn to react to specific microbes, environmental agents and physical damage. They are rich in blood vessels and nerves and they both play crucial immune and neuroendocrine roles. Our skin and gut are in a constant struggle, fighting to maintain homeostasis with their microbiota, and these tissues use similar tactics to keep their microbiota in check. For example, they both frequently shed their outer cells, they also both secrete protective fluids with powerful bioactive substances, including interferon, interleukin, and growth factors, and they both work closely with the immune system to modulate inflammation.

Because of their common embryonic origin, it is unsurprising that gut and skin epithelial cells will respond to many of the same biologically active molecules, although not necessarily in the same way or to the same extent. With both tissues connected by circulating blood, it is easy to see how oral probiotics could affect both the gut and skin and so play their part in the gut–skin axis [2].

The gut–skin axis acting in inflammatory gut and skin conditions

Inflammation is triggered by many different inflammatory mediators. For example, interleukin 22 (IL-22) is one amongst many important proinflammatory cytokines, which are released to control the gut microbiota. It is considered a key mediator leading to heightened pathogen resistance. IL-22 is produced by the immune cells situated just below the gut epithelium. It acts primarily on epithelial cells and (in the gut) it helps to manage the three-way interaction between the immune system, the gut microbiota and the gut epithelial cells. It regulates the expression of genes involved in the maintenance of epithelial barrier integrity (including those responsible for adaptations in the mucus layer and tightening of cell–cell junctions), and for the production of various bactericides. In a classic feedback loop, these responses affect the microbiota composition, which in turn becomes less threatening to the gut and so the production of more IL-22 stops.

IL-22 also upregulates the expression of genes in skin for various antimicrobials, including psoriasis, calgranulin A and calgranulin B. However, unlike in the gut, the presence of IL-22 in skin results in inhibition of cell differentiation and upregulated expression of enzymes involved in inflammatory skin disease (matrix metalloproteinases ─ MMP1, collagenase 1 and MMP3). This creates inflammatory conditions associated with diseases such as psoriasis, and may account for the differences in their skin microbiota when compared to non-sufferers. It is interesting to note that sufferers of psoriasis have high levels of IL-22 in their plasma, and these levels are proportional to the severity of their disease. Also, treatments that reduced the expression of IL-22 (and IL-22-regulated genes) have been shown to lessen the degree of psoriasis [3].

Is it possible that the plasma IL-22 was produced by the immune cells situated just below the gut epithelium in response to a rebellious gut microbiota? If so, then this is a good illustration of the gut–skin axis at work. When considering that IL-22 is just one example of the many potent cytokines produced by the gut, it is not surprising that skin often responds when the gut is in trouble.

It is tempting to speculate that future research will discover one or more inflammatory cytokines that bring about aspects of acne, in the plasma of acne sufferers. However, for the case of certain skin conditions, it should be noted that IL-22 takes not only a proinflammatory role – deficiency of IL-22 has actually been observed in association with chronic inflammatory acne inversa, pointing towards anti-inflammatory action [4]. The work leads to the conclusion that IL-22 is capable to perform both pro- and anti-inflammatory responses, depending on tissue microenvironment including cytokine milieu.

How gut microbiota affects acne

It is not just the proinflammatory cytokines produced when the gut is out of balance that exacerbate inflammatory skin diseases such as acne. Studies show that short chain fatty acids (SCFAs), produced when the gut breaks down fibre, influence the composition of the skin microbiota. By inhibiting Staphylococcus epidermidis from forming protective biofilms, SCFAs give Cutibacterium acnes an advantage over S. epidermidis in their competitive tussle, while also encouraging other microbes involved in regulating skin inflammation [5,6]. Because of the perfect storm of contributing factors that come together to create acne, simply rebalancing to reduce the production of proinflammatories and taking care with fibre intake, will not be enough to control acne in every sufferer. For example, it will obviously not help people who are predisposed to have raised levels of the hormone, dehydroepiandrosterone sulfate (DHEAS), and so on, but it should go a long way to help many others [7].

Probiotics – helping to rebalance and repopulate the gut

Unfortunately, there have only been a few studies comparing the gut microbiota of people with and without acne. However, those that have been published do suggest that there are significant differences and that the gut microbiota of acne sufferers is less healthy. The gut microbiota of acne sufferers is reported to be less biodiverse with a higher ratio ofBacteroidetes to Firmicutes. Changes in this ratio is considered by many to be an indicator of dysbiosis. The levels of Lactobacillus, Bifidobacterium, Butyricicoccus, Coprobacillus and Allobaculum in acne sufferers were also found to be lower when compared with controls [8,9,10]. Remembering that the gut─skin axis is a two-way conversation facilitated by a continually learning host immune system, the cytokines from acne skin may be preventing the gut microbiota from naturally recovering. Probiotics could therefore be the key to re-establishing a healthy gut microbiota, even during severe and long-standing acne breakouts.

Among the probiotic strains of live microorganisms that are proving to be effective for acne, is a blend of Bifidobacterium breve BR03 DSM 16604, Lacticaseibacillus casei LC03 DSM 27537, and Ligilactobacillus salivarius LS03 DSM 22776. In a recent randomized, double-blind clinical study, involving 114 subjects with mild to moderate acne, a 40% reduction in superficial inflammatory lesions was seen after 8 weeks in the cohort taking this blend, which compared well with the placebo group who experienced only a 10% reduction [11]. In an older study, where Lactobacillus rhamnosus SP1 was used in a dietary supplement, a 32% reduction in acne lesions was seen and the expression of genes implicated in insulin signalling were normalized.

An improvement in the appearance of the adult acne in the group taking the dietary supplement was also observed in this study. These researchers were investigating the notion that acne is associated with diets that are high in the type of carbohydrates that cause rapid rises in blood sugar [12]. Insulin growth factor 1 (IGF-1) is released in response to raised blood sugar. Its main function is to increase glucose uptake by tissues; however, IGF-1 also stimulates sebum production [13]. This increase in sebum might be the link between sugary diets and worsening acne. In passing, it is worth noting that when carbohydrate is plentiful (as in a sugary diet), the ratio of Firmicutes to Bacteroidetes favours Firmicutes in the gut microbiota, and yet the opposite was reported in the study comparing the gut microbiota of acne sufferers with healthy people [8]. This suggests that the subjects in this particular study did not have sweet diets.

Another study looked to see if the efficacy of the antibiotic minocycline could be boosted by probiotics. They concluded that probiotics could be used to reduce inflammation and that they worked synergistically with the minocycline [14,22].

Topical probiotics and acne

Topical probiotics have been shown to moisturize, encourage epidermal repair and lipid production. They can bring about an increase in cytokines and antibodies, restore the immune system’s overall balance and reduce pathogens and toxic metabolites [6]. The increasing number of probiotic cosmetics products includes deodorants, primers, balms, soap bars, foundation, cleansers, exfoliants, gels, masks, serums and creams. Most, however, do not comply with the essential criteria required to make a science-based probiotic claim.

They are not using live, genetically and phenotypically characterized microbial strain(s), for a purpose validated by peer-reviewed published paper(s) [15,16]. Their labels show that many of these cosmetics are based on non-living lysates and ferments, from microbes such as Lactococcus, Lactobacillus, Lactobacillus bulgaricus, Lactobacillus acidophilusLactobacillus caseiBifida, Streptococcus thermophilus, Leuconostoc and Saccharomyces.

However, as effective as these cosmetics are, their efficacy cannot be said to be due to science-based topical probiotics [17]. The pioneering probiotic brand, Mother Dirt, does claim to include live bacteria in all of their products. They have an ‘Active Probiotic System’ composed of three products, where their third product ─ AO+ Restorative Mist ─ contains live Nitrosomonas eutropha and does arguably satisfy most of the probiotic criteria. The good news for acne sufferers is that a 21-day clinical trial of their Active Probiotic System had 90% of subjects agreeing that the product improved their acne. This positive result may not of course be because of the probiotic in their AO+ Restorative Mist. Research shows that the ammonia-oxidizing bacteria N. eutropha D23, through mechanisms involving the anti-inflammatory cytokine IL-10, inhibits T helper 2 (Th2) cell polarization and so may have a positive effect on inflammatory skin diseases [18]. Interestingly, especially for those using snail slime as a cosmetic ingredient, a study by Polish researchers showed a reduction in acne flare-ups when the lactic acid bacteria (LAB) Weissella viridescens, isolatedfrom snail slime (Helix aspersa müller), was used both topically and orally. W. viridescens UCO-SMC3 was shown in vitro to inhibit C. acnes growth and to obstruct C. acnes from bonding with keratinocytes [19].

An increasing number of live microbes are being shownto limit the growth of C. acnes and other acne-associated microbes in in vitro studies. Despite not yet having clinical trial data to show these microbes improving acne skin, the in vitro results justify the expectation that further studies will identify these microbes as anti-acne probiotics. For example, a probiotic strain of LAB (Lactobacillus acidophilus A001F8) was successfully combined with Curcuma longa extract, and the combined antimicrobial effect against C. acnes was synergistic [20]. In another study, a blend of L. casei, Lactobacillus plantarum, Lactobacillus gasseri and Lactobacillus lactis significantly inhibited the growth of C. acnes [6]. Similarly, probiotics that induce ceramides or bacteriocins, which are known to improve skin barrier function and to be anti-inflammatory and antimicrobial against C. acnes, may also one day be shown to be anti-acne probiotics [21,22,23].  

In a press release from November 2021, S-Biomedic reported the successful completion of a Phase 2 cosmetic study for acne-prone skin, using the skin’s own bacteria. Topically applied skin probiotic strains CA-31 and CA-81 showed statistically significant improvements in reducing redness and improving the number of acne lesions. Commercialized as the active ingredient CutilModulis, this is heralded as the first true LiveSkin Probiotics™ probiotic coming to the market that is backed by extensive clinical and safety research [24].


The close relationship between the gut and skin warrants the use of oral and topical probiotics to address inflammatory skin conditions. There is no doubt from the peer-reviewed published research that probiotics can have a positive impact on some types of acne. Because of the perfect storm of causes that underpin acne, it is unlikely that probiotics alone will solve the acne dilemma; however, they may turn out to be the missing factor. Undoubtedly, a lot more studies are needed before dermatologists can confidently prescribe effective probiotic regimes.

The next time you are tempted by that sugarydoughnut, or you are tempted by snails on the menu, remember we are all what we eat, and your choice could have effects on your skin as well as satisfying your hunger.

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