Acne, Microbiome, and Probiotics: The Gut–Skin Axis

Introduction

Besides the gut, the epidermis possesses one of the largest surface areas for direct contact and colonisation with microorganisms, with approximately 10^12 bacteria inhabiting the skin, compared with 10^14 in the intestines. Recent studies have geared focus towards understanding the immunomodulatory potential of these two organs on each other, with findings that point to the ability of the gut microbiota to alter the function of the immune system to disrupt skin homeostasis, and subsequently balance of the skin microbiota (Sánchez-Pellicer et al., 2022).

Acne vulgaris is one such condition thought to be driven by this complex bidirectional interaction, where it is characterised by inflammation of the pilosebaceous units of the skin. Onset of this condition has been noted to coincide with puberty and subsequent elevated sebum production, resulting in a higher prevalence in groups such as adolescents and young adults, and the appearance of comedones, papules, pustules, nodules, or scars on the skin (Sánchez-Pellicer et al., 2022).

While the specific mechanism by which the gut microbiota enacts such control over the development of acne has yet to be properly established, several studies have noted a relationship between intestinal dysbiosis and presence of acne on the skin. The mTOR (mammalian target of rapamycin) pathway is also thought to play a role, with defects in this pathway disrupting processes essential to skin homeostasis and even modifying gut microbiome composition, which may inadvertently trigger acne pathogenesis or inflammation (Sánchez-Pellicer et al., 2022).

The objective of this paper was to review the effectiveness of probiotic treatments as adjuvant or alternative therapies in treating this skin condition by modulating the gut–skin axis possibly involved in regulating the cutaneous microbiome. It also examines the influence of lifestyle factors such as diet that act along the gut-skin axis to influence skin homeostasis and acne pathogenesis (Sánchez-Pellicer et al., 2022).

Results

The ability of certain probiotics to produce antimicrobial substances may permit control of acne symptoms by inhibiting the growth of C. acnes. Strains of bacteria such as Streptococcus salivarius (Bowe et al., 2006), Lactococcus sp. HY 449 (Oh et al., 2006), and Lactobacillus salivarius LS03 (Deidda et al., 2018) secrete bacteriocins (a type of antimicrobial peptide) that can exert this inhibitory effect.

Glycerol fermentation by S. epidermidis is capable of producing succinic acid that can restrict C. acnes growth by decreasing the intracellular pH of the C. acnes cells and interfering with their metabolism and ability to properly function (Wang et al., 2014).

Other probiotic species like Streptococcus thermophilus (Di Marzio et al., 1999) can increase production of ceramides like phytosphingosine (Pavicic et al., 2007) that promote water retention in the skin, anti-inflammation, and antimicrobial activity against C. acnes. These three factors act to reduce severity of acne symptoms and lesions.

Biofilms, which are an aggregate community of bacterial cells contained within a polymer matrix that adheres to the skin surface, are another feature of C. acnes that increases its resistance to antibiotics by preventing them from directly interacting with any of the bacterial cells contained within the matrix. Lactobacillus and Bifidobacterium species have demonstrated the ability to disrupt the biofilms of pathogenic bacteria such as C. acnes to reduce their virulence and possibly increase their sensitivity to other treatments (Lopes et al., 2016).

Probiotics can be administered either orally or topically, with multiple trials reporting successes in treating acne using either treatment. 

Oral probiotics have the potential to reduce symptoms associated with acne through modulation of the intestinal microbiota and promotion of anti-inflammatory effects. 12-weeks of orally administering a probiotic mixture containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum, in combination with a minocycline antibiotic found that within 8 weeks, patients in the combination group demonstrated significantly better efficacy in lesion and inflammation reduction than groups receiving either probiotic or antibiotic alone (Jung et al., 2013).

Topical treatments instead work by directly inhibiting the growth of C. acnes in the pilosebaceous unit, with one clinical trial reporting a similar reduction in the appearance of mild-to-moderate acne lesions on the skins of patients treated with either a 2.5% benzoyl peroxide lotion, or a probiotic-derived lotion containing Lactobacillus paracasei MSMC 39-1 (a strain known to restrict C. acnes growth) after 4-weeks of treatment. However, the group receiving probiotic-derived lotion reported fewer treatment-associated side effects than the 2.5% benzoyl peroxide group, highlighting its potential as a safe yet effective alternative (Sathikulpakdee et al., 2022).

A high fat, Western diet typically associated with high consumption of ultra processed foods and sugar leads to a loss of diversity of gut microbiota, and can promote formation of acne lesions. Overconsumption of red meat, which is a typical feature of the Western diet, stimulates the mTOR pathway to increase the rate of lipogenesis of the sebaceous gland and subsequent inflammation. This demonstrates the ability of the gut microbiome to shape the acne inflammatory response, and highlights the importance of maintaining balance along the gut-skin axis through diet (Sánchez-Pellicer et al., 2022).

Table summarising the effects of various probiotic treatments on the skin microbiome

Future Directions

Postbiotic formulations containing the metabolic byproducts or lysates of bacteria have shown promise as another potential bioactive treatment for acne by promoting antibacterial, anti-inflammatory, and immunomodulatory effects. The lack of live bacteria (unlike in probiotics) also makes these formulations suitable for those with weakened immune systems (Prajapati et al., 2025).

Genetic engineering of probiotic strains, using approaches like the CRISPR-Cas9 system, can be used to improve the stability, specificity, and functionality of these bacteria during targeted therapeutic delivery for more effective results in treating diseases such as acne, as well as developing customised probiotics for more personalised therapies (Ma et al., 2022).

Conclusions

The gut-skin axis plays a crucial role in maintaining skin homeostasis and overall balance of microbial communities inhabiting the skin, something that becomes especially clear when taking lifestyle factors such as diet into account, with a high fat, Western style diet triggering acne pathogenesis, and further pointing to gut influence in modulating skin health.

Utilising this dynamic to promote skin health and reduce acne symptoms can be achieved by targeting the gut microbiome in a manner that induces positive downstream effects in the skin. Oral probiotics in particular show promise as effective treatments for the treatment of acne that work by modulating the gut-skin axis. Topical probiotics show similar potential, although these bypass the gut-skin axis in most cases to directly tackle skin pathogens.

Clinical trials looking to evaluate the effectiveness of topical and oral probiotics in treating acne remain scarce, with many conducted thus far involving in vitro or animal models that do not accurately reflect human biology. Further studies are also needed to properly elucidate the exact mechanisms by which this intestinal modulation is able to influence acne progression along the skin as a way to aid the development of more effective oral treatments (Sánchez-Pellicer et al., 2022).

References

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