Probiotics for Acne: Oral vs. Topical

Summary

Acne, the most common skin condition in the United States,^[1] can cause discomfort, scarring, and hyperpigmentation if left untreated. Treatment approaches range from the traditional aim of reducing the skin’s bacterial burden through antimicrobials to new tactics of promoting bacterial balance with probiotics. Current research supports the role of oral and topical probiotics in the treatment of acne vulgaris. Proposed mechanisms of action of probiotics include reduction in inflammation and production of bactericidal substances. The use of oral probiotics and Lactobacillus and Bifidobacterium strains is currently supported by data, but additional research may identify routes of administration and formulations that can lead to optimal treatment of acne.

Introduction

The bacteria that reside on our skin and in our gastrointestinal system are collectively known as our microbiome. This microbiome contributes to homeostasis of organ systems, and disruptions are associated with clinical disease. The skin-gut health axis (Figure 1) depicts how imbalances in the skin and gut microbiomes may contribute to common skin conditions. This theory links changes in the gut microbiome to greater intestinal permeability, systemic inflammation, and in turn, the development of acne vulgaris.^[2]

Acne vulgaris is a chronic skin condition characterized by hyperkeratinization, increased sebum production, and Cutibacterium acnes (C. acnes) colonization and overgrowth in hair follicles, with subsequent inflammation.^[3] Acne lesions provide an anaerobic environment where C. acnes, an opportunistic pathogen, can flourish. Typically, other bacteria are also present in these lesions, but C. acnes is the most prevalent species. C. acnes is associated with the main pathogenic factors in acne: bacterial colonization and inflammation.^[3,4] Physiologic changes and the loss of biodiversity or disruption of its balance in the skin environment can select for pathogenic variants of C. acnes, resulting in worsening acne.^[5] For example, a skin surface with excess sebum may encourage growth of C. acnes strains that cause greater inflammation than other strains. Staphylococcus epidermidis inhibits C. acnes growth and related inflammation, and disruptions in the two populations contribute to dysbiosis.^[5]

Many acne treatments aim to address the bacterial environment on the skin. Traditionally, antibiotics and the associated eradication of most skin bacteria, were a mainstay of acne treatment. However, emerging knowledge of our microbiome suggests that rebalancing microbial flora, rather than eradicating it, may be a therapeutic goal for inflammatory conditions, including acne. 

Figure 1: Interaction between gut microbiome, skin microbiome and common skin conditions

Credit: Salem, et al., Front. Microbiol, 2018^[6]

Basis for Probiotic Administration

Our gut and skin microbiomes influence each other and contribute to skin health by immune modulation, altered production of inflammatory and anti-inflammatory cytokines, and production of metabolites that influence the skin and its bacterial inhabitants.^[7] In an in vitro cell culture skin model, the probiotic strain Lactobacillus paracasei NCC2461 demonstrated dose-dependent inhibition of CD-4+ T cell activation and induction of the anti-inflammatory cytokines IL-10 and TGF-b.^[8] At the skin level, this contributed to the preservation of skin homeostasis via skin immune modulation and reinforcement of the skin’s barrier function. Overall, studies conclude that the gut and skin function together for skin health.^[7]

Probiotics aim to alter the skin environment to prevent overcolonization of C. acnes and other acne-causing bacteria. Probiotics directly inhibit C. acnes via the synthesis of antibacterial proteins and organic acids by certain bacterial strains (Table 1).^[9] Additionally, the production of short-chain fatty acids on the skin can inhibit C. acnes growth.^[4] Lactic acid^[10] and ceramide,^[11] produced following topical probiotic administration, exhibit direct antimicrobial activity to C. acnes.

Oral Probiotics for Acne

Oral probiotics have theoretical evidence and some clinical evidence for use in the treatment of acne.^[4] Oral probiotics are associated with a reduction in oxidative stress, which could attenuate the inflammation accompanying acne. A clinical trial investigating the use of oral probiotics along with oral antibiotic treatment indicated a significant decrease in total acne lesion counts.^[13] Additionally, there were fewer vaginal candidiasis events than in subjects given antibiotics alone.^[13] This supports the use of oral probiotics as an adjunct treatment with oral antibiotics.^[9,13]

Studies

A large-scale review on acne vulgaris and probiotics concluded that oral probiotic administration was associated with improved acne outcomes.^[9] In addition, a randomized, prospective open-label trial demonstrated that consumption of Lactobacillus acidophilus, Lactobacillus delbrueckii bulgaricus, and B. bifidum was as effective as minocycline in the treatment of acne, with a 67% reduction in lesion counts after twelve weeks and fewer side effects. All groups (probiotics alone, minocycline alone, and probiotic and minocycline combination) saw significant improvements in noninflamed acne lesion counts every four weeks for twelve weeks of treatment. The combined group had significantly lower lesion counts than both groups (p = 0.03 for probiotic alone; p = 0.001 for minocycline alone). In conclusion, combining the oral probiotic and minocycline had greater effectiveness with fewer adverse effects than minocycline or probiotics alone.^[13]

Another randomized-controlled study with twenty subjects indicated that oral administration of Lactobacillus rhamnosus SP1 resulted in improved or markedly improved adult acne compared to placebo (OR = 28.4).^[12] Researchers also measured gene expression on the skin of IGF-1, a hormone shown to promote acne, and FOXO1, a transcription factor whose deficiency is associated with acne pathogenesis. The group receiving the oral probiotic also showed a 32% reduction in IGF-1 and a 65% increase in FOXO1.^[12] This study, although small, depicted marked acne improvement with a measured mechanism of action.

Topical Probiotics for Acne

Studies

A mouse model found marked suppression of C. acnes-induced inflammation with intralesional and topical application of succinic acid, which is produced by Staphylococcus epidermidis upon glycerol fermentation. Researchers proposed that this antagonistic behavior between S. epidermidis and C. acnes could be exploited for future development of probiotics to treat acne and other skin conditions.^[4]

Another study used vitro testing using human skin cells to identify bacterial strains that inhibited C. acnes and S. aureus growth for a skin cream treatment. The cream contained equal amounts L. rhamnosus GG, L. plantarum WCFS1 and L. pentosus KCA1.^[10] Ten subjects with mild to moderate acne applied the probiotic-containing cream twice daily for eight weeks. Compared to controls, subjects receiving the Lactobacillus cream saw an overall improvement of acne symptoms with significant reductions in inflammatory lesions and comedone counts. They also had a decreased relative abundance of Cutibacterium acnes, indicating a shift in the skin microbiome. Researchers concluded that other lactic acid-producing bacteria such as Streptococcus salivarus might be beneficial for acne treatment as well.

Conclusion

The skin microbiome is a competitive and dynamic environment, and alterations in its composition are linked to acne pathogenesis.^[3,4,9] Using oral and topical probiotics to promote microbiome diversification and balance is an exciting new avenue of acne treatment. This approach can accompany antibiotic treatments with aims to mitigate adverse effects on microbiomes beyond the skin.^[13] Probiotics carry little risk, but warning patients of the potential for gastrointestinal upset and bloating can be helpful.

Practical Tips

1. Adding an oral probiotic to an acne treatment regimen involving oral antibiotics could help improve treatment outcomes and prevent adverse effects from antibiotic use.
2. Lactobacillus, Bifidobacterium and some Streptococcus species have promise for use in acne treatment, but more studies are needed to define the best formulations for probiotics.
3. There is greater evidence for the use of oral probiotics in treating acne than topical probiotics, but research in both areas is ongoing.