PracticalDermatology

The first part of this two-part series reviewed probiotics provided via oral supplementation to support the management of atopic dermatitis. (Read part 1 in the August edition, online at PracDerm.com/ProbioticsPt1.) Here is a look the evidence of topically applied probiotics in AD, as well as research on probiotics in acne and psoriasis.

Topical Probiotics for AD

Lactobacillus sakei proBio-65 was isolated from homemade kimchi, and a topical solution was used in a split-body study in 28 AD patients.¹ The treated sides had significantly lower TEWL and VAS values and significantly higher skin capacitance values over time than the control sides. A study with 31 adults showed that application of topical Lactobacillus johnsonii NCC533 to AD lesions twice daily for three weeks led to reduction in S. aureus load, which correlated with decrease in SCORAD.² Another study showed that two weeks of topical administration of Streptococcus thermophilus S244 cream in patients with AD led to a significant improvement in erythema, scaling and pruritus.³ Gueniche et al. showed that a topical cream containing lysate of Vitreoscilla filiformis, a Gram-negative bacterium found in thermal spring water, led to improvement in mEASI after four weeks with a 42.9 percent decrease in mEASI, whereas vehicle treated side showed a decrease by 24.8 percent only (p = 0.008).⁴ A slightly later study showed that topical Vitreoscilla filiformis led to significant improvement of SCORAD (P=0.0044), pruritus (P= 0.0074),and TEWL in patients with AD.⁵ Finally, twice daily application of a topical ointment with L. reuteri DSM 17938 showed statistically and clinically significant improvement of the SCORAD index in 36 adult subjects with AD after four and eight weeks.⁶

Acne

Acne vulgaris affects approximately 50 million people in the US,⁷ where it is the most common skin condition and the top reported cause for dermatology visits, accounting for about one-fourth of US dermatologists’ patient volume.⁸ Despite the number of over-the-counter and prescription remedies, acne remains an area of significant unmet medical need as current treatments are either marginally effective (topical antibiotics, topical retinoids), associated with serious risks (oral retinoids), or have led to the development of resistant strains of C. acnes (antibiotics).⁹

Possible Mechanisms for Probiotics in Acne. Disruption of the gut microbiome has also been implicated in acne pathogenesis via the gut-skin axis,¹⁰ and 54 percent of acne vulgaris patients have marked alterations to intestinal microflora.¹¹ This suggests the potential utility of oral probiotics.

One potential benefit of systemic probiotics is the reduction of inflammation in acne, probably caused by the downregulation of gene expression related to the release of inflammatory cytokines and the recruitment of pathogenic CD8 T cells while activating Treg cells.¹² Probiotics may also decrease sebum content, which can lead to lower follicular colonization by C. acnes and therefore decrease inflammation.¹³ There is also growing evidence in recent years of the connection between dietary components, most notably low-fiber carbohydrates, and risk of acne.¹⁴ Probiotics may also bring down the glycemic load and reduce IGF-1 signaling, thereby decreasing the predisposing factors of acne formation, such as keratinocyte proliferation and sebaceous gland hyperplasia.¹⁵ Furthermore, acne vulgaris is associated with overgrowth of C. acnes on the skin. Studies have shown that bacterial members in the skin microbiome could undergo fermentation to rein in the overgrowth of C. acnes, which could be used to develop topical probiotics.¹⁶

However, compared to AD, the efficacy of probiotics for the treatment of acne is far less studied, particularly in human trials. Since there is generally only one study per strain, it is harder to compare the efficacy between strains. Nevertheless, here we note in vivo studies of different strains of probiotics for the treatment of acne. (See Table 1)

Lactobacillus.Lactobacillus is one of the most studied strains for the treatment of AD and remains the same for acne.¹⁷ As early as the 1930s, physicians made reference to the popularity of L. acidophilus cultures among the general public as an internal means to treat acne. As far back as 1961, Robert H. Silver found that when probiotics such as Lactobacillus acidophilus and Lactobacillus bulgaricus were supplemented in 300 acne patients, improvement in acne occurred in 80 percent of subjects, particularly in those with inflammatory lesions.¹⁸ Muizzuddin, et al. showed that a reduction in acne count, size, and associated erythema was again noted during a clinical study of Lactobacillus plantarum 5% extract, although these findings were not supported with the 1% extract, suggesting the effects may be dose dependent.¹⁹

L. rhamnosus GG was also studied in the treatment of acne, and it was found that 12 weeks of LGG administration normalized skin expression of insulin signaling genes in acne areas, a molecular change that was accompanied by a significant improvement in acne appearance.²⁰ Growing evidence indicates that IGF1 and FOXO1 dysregulation may be involved in the pathogenesis of acne, and the normalization of their skin expressions following 12 weeks of LGG supplementation confirms that probiotics may act as clinically useful modulators of the gut-skin axis.

Interestingly, IGF1 and FOXO1 have been suggested to play a crucial role in the pharmacological action of oral isotretinoin, one the most effective drugs in the treatment of acne.^21-24

Other studies have paired lactobacillus strains with other bacterial strains, to promising effects. A study with 40 adults showed that the adults supplemented with L. acidophilus and Bifidobacterium bifidum experienced improved clinical outcome and resolution of acneiform lesions compared to the non-supplemented group, as well as demonstrated better tolerance for oral antibiotics.²⁵ Another randomized-controlled trial from Korea assigned acne patients to receive fermented milk containing L. bulgaricus and S. thermophilus strains with 200mg of lactoferrin or fermented milk only.²⁶ The group receiving the lactoferrin-enriched fermented milk showed a greater decrease in total lesion count compared to fermented milk alone (56 percent versus 32.2 percent). However, the substantial decrease noted by the administration of an oral probiotic alone further supports the role of probiotics as an adjuvant in acne treatment. Sebum content and free fatty acid concentration also decreased by 50 percent or more in the skin of patients taking this oral probiotic.

Another clinical trial demonstrated that oral antibiotics and probiotics might provide synergistic benefits, specifically for inflammatory acne.²⁷ Forty-five females, aged 18 to 35 years, were randomly assigned to one of three groups: probiotic supplementation only, minocycline only, or both probiotics and minocycline. The probiotics studied included a combination of Lactobacillus acidophilus, Lactobacillus delbrueckii bulgaricus and B. bifidum. Probiotic supplementation was as effective as minocycline in the treatment of acne, with 67 percent lesion reduction after 12 weeks and fewer side-effects, and a combination of this oral probiotic and minocycline had even greater effectiveness. Furthermore, two patients from the minocycline-only group developed vaginal candidiasis.

While lactobacillus strains are the most studied probiotic strains for acne, other probiotic strains have been studied to preliminary but promising results. Enterococcus faecalis is a lactic acid bacteria found in the human gut and found to produce bacteriocin(s) having antimicrobial activity against C. acnes.²⁸ In a study of 70 individuals, topical Enterococcus faecalis SL-5 significantly decreased inflammatory acne lesions, like pustules, when compared to the placebo lotion. Nitrosomonas eutropha is an ammonia-oxidizing bacteria that converts ammonia to nitrite, which is known to have antibacterial properties, and to nitric oxide, a signaling molecule known to regulate inflammation and vasodilation (Therapeutics, n.d.). A Phase 2b study with 385 adults has also demonstrated that application of Nitrosomonas eutropha led to a 2-point reduction in Investigator’s Global Assessment of acne severity compared with control and a trend in the reduction of the number of inflammatory lesions (p=0.03).

Psoriasis

Psoriasis is a chronic inflammatory skin condition characterized by erythematous, scaly, and often pruritic plaques. There is some evidence that the alteration of the skin microbiome may trigger activation of the Th17 pathway in psoriasis.^29,30 Compared to non-psoriasis patients, the skin flora of psoriasis patients shows decreased microbial diversity and differences in the relative number of bacteria.^31,32 While studies investigating the role of probiotics in psoriasis are lacking, there is some evidence that probiotics may exert beneficial immunoregulatory effects by reducing inflammation. (See Table 2)

In patients with psoriasis, oral administration of Bifidobacterium infantis 35624 for eight weeks led to significantly decreased levels of inflammatory C-reactive protein and tumour necrosis factor-a, although it is unclear whether this was accompanied by clinical improvements.³³ One case study looked at the Lactobacillus sporogenes treatment of a 47 years old woman with pustular psoriasis.³⁴ She did not respond to the typical treatments of steroids, dapsone, and methotrexate and was starting to develop steroid toxicity. All medications were stopped and the patient was given probiotic L. sporogenes three times a day. After 15 days, the fever defervesced, lesions started ameliorating and no new lesions were observed. After six months, she was free of lesions.

Finally, a recent study of 90 adults with psoriasis involved 12 weeks with oral probiotic treatment (Bifidobacterium longum CECT 7347, B. lactis CECT 8145 and Lactobacillus rhamnosus CECT 8361).³⁵ At the 12-week follow-up, 66.7 percent of patients in the probiotic group and 41.9 percent in the placebo group showed a reduction in Psoriasis Area and Severity Index of at least 75 percent (p<0.05). A clinically relevant difference was observed in Physician Global Assessment index: 48.9 percent in the probiotic group achieved a score of 0 or 1, compared with 30.2 percent in the placebo group. Furthermore, during the interventional period of the study, the probiotic group showed a disappearance of the problematic Rhodococcus, a bacteria related to septicaemia and biofilm production,³⁶ and an increase in Collinsella and Lactobacillus, bacteria associated with better gut health.³⁷

Overall, the use of probiotics for psoriasis is not well-established and it is too early to determine which strains are superior to others. However, the studies noted show that there may be several Lactobacillus and Bifidobacterium strains that show promise.

Conclusion

Though the evidence is limited and sometimes conflicting, there are promising results about the role of probiotics in the treatment of different dermatological conditions. A further breakdown of the probiotic strains leads to more specific results of which strains have shown more evidence to treat these conditions. Additional well-designed, larger population-based trials are needed to better understand the role of probiotics in these conditions.

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2. Blanchet-Réthoré, Sandrine, Valérie Bourdès, Annick Mercenier, Cyrille H. Haddar, Paul O. Verhoeven, and Philippe Andres. 2017. “Effect of a Lotion Containing the Heat-Treated Probiotic Strain Lactobacillus Johnsonii NCC 533 on Staphylococcus Aureus Colonization in Atopic Dermatitis.” Clinical, Cosmetic and Investigational Dermatology 10 (July): 249–57.

3. Di Marzio, Luisa, Carla Centi, Benedetta Cinque, Silvio Masci, Maurizio Giuliani, Anna Arcieri, Luigi Zicari, Claudio De Simone, and Maria Grazia Cifone. 2003. “Effect of the Lactic Acid Bacterium Streptococcus Thermophilus on Stratum Corneum Ceramide Levels and Signs and Symptoms of Atopic Dermatitis Patients.” Experimental Dermatology 12 (5): 615–20.

4. Guéniche, Audrey, Anca Hennino, Catherine Goujon, Karima Dahel, Philippe Bastien, Richard Martin, Roland Jourdain, and Lionel Breton. 2006. “Improvement of Atopic Dermatitis Skin Symptoms by Vitreoscilla Filiformis Bacterial Extract.” European Journal of Dermatology: EJD 16 (4): 380–84.

5. Gueniche, A., B. Knaudt, E. Schuck, T. Volz, P. Bastien, R. Martin, M. Röcken, L. Breton, and T. Biedermann. 2008. “Effects of Nonpathogenic Gram-Negative Bacterium Vitreoscilla Filiformis Lysate on Atopic Dermatitis: A Prospective, Randomized, Double-Blind, Placebo-Controlled Clinical Study.” The British Journal of Dermatology 159 (6): 1357–63.

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16. Wang, Yanhan, Sherwin Kuo, Muya Shu, Jinghua Yu, Stephen Huang, Ashley Dai, Aimee Two, Richard L. Gallo, and Chun-Ming Huang. 2014. “Staphylococcus Epidermidis in the Human Skin Microbiome Mediates Fermentation to Inhibit the Growth of Propionibacterium Acnes: Implications of Probiotics in Acne Vulgaris.” Applied Microbiology and Biotechnology 98 (1): 411–24.

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20. Fabbrocini, G., M. Bertona, Ó. Picazo, H. Pareja-Galeano, G. Monfrecola, and E. Emanuele. 2016. “Supplementation with Lactobacillus Rhamnosus SP1 Normalises Skin Expression of Genes Implicated in Insulin Signalling and Improves Adult Acne.” Beneficial Microbes 7 (5): 625–30.

21. Melnik, Bodo C., and Gerd Schmitz. 2009. “Role of Insulin, Insulin-like Growth Factor-1, Hyperglycaemic Food and Milk Consumption in the Pathogenesis of Acne Vulgaris.” Experimental Dermatology 18 (10): 833–41.

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33. Groeger, David, Liam O’Mahony, Eileen F. Murphy, John F. Bourke, Timothy G. Dinan, Barry Kiely, Fergus Shanahan, and Eamonn M. M. Quigley. 2013. “Bifidobacterium Infantis 35624 Modulates Host Inflammatory Processes beyond the Gut.” Gut Microbes 4 (4): 325–39.

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