The chronic use of antibiotics for inflammatory skin conditions like acne vulgaris leads to antibiotic resistance and gut dysbiosis. Growing evidence suggests a gut-skin axis, where gut bacteria influence skin health through various communication mechanisms. Previous research indicates that the gut microbiome may play a role in conditions such as psoriasis, acne, rosacea, and atopic dermatitis. Oral probiotics have shown anti-inflammatory effects, improving conditions like atopic dermatitis and potentially acne. However, the mechanisms by which probiotics interact with the skin and influence biomechanical properties like sebum production, TEWL, and skin hydration remain unclear. This study aimed to prospectively evaluate the effects of oral spore-based probiotics on skin biomechanical properties and sebum production, focusing on acne as a multifactorial disease involving keratinocyte hyperproliferation, sebum production, inflammation, and scarring. The study also assessed changes in gut microbiome and plasma SCFAs to correlate with skin changes.

The literature review section highlights the prevalent use of antibiotics in treating inflammatory dermatological conditions, including acne, rosacea, and hidradenitis suppurativa. The drawbacks of prolonged antibiotic use, namely the development of drug-resistant bacteria (Cutibacterium acnes, Staphylococcus aureus) and consequent gut dysfunction, are emphasized. The study underscores the emerging interest in the gut-skin axis and the potential influence of the gut microbiome on skin conditions. Studies demonstrating the impact of the gut microbiome on psoriasis, acne, rosacea, and atopic dermatitis are cited, along with evidence supporting the anti-inflammatory effects of probiotics. The authors point to previous research showing beneficial effects of oral probiotics on skin conditions, such as atopic dermatitis and acne, and the potential role of probiotics in improving skin hydration and reducing TEWL. However, a lack of research specifically addressing the impact of probiotic supplementation on sebum production and skin barrier properties is noted, leading to the rationale for the current study.

This 8-week, single-blinded, placebo-controlled study (NCT03605108) enrolled 25 healthy participants (mean age 30.8 years; range 19–62 years) with or without noncystic acne. Participants were excluded based on several criteria, including recent topical or systemic antibiotic use, high BMI, recent hormonal birth control changes, isotretinoin or topical retinoid use, use of medications affecting blood lipids, and smoking. The study design involved three visits (baseline, week 4, and week 8). Participants received placebo capsules for the first four weeks, followed by four weeks of spore-based probiotics (Megasporebiotic) containing 4 billion spores from various Bacillus strains. Blood and stool samples were collected at each visit to assess SCFAs, inflammatory cytokines (TNF-α, LPS), and markers of intestinal permeability (FABP-2, zonulin). Facial photography, sebum production, TEWL, and skin hydration measurements were also performed. Skin and gut microbiome samples were collected using swabs and analyzed through 16S rRNA gene sequencing. Plasma SCFAs were quantified using GC-MS. Statistical analysis utilized repeated measures Wilcoxon tests, with p < 0.05 considered significant. The primary outcome measure was the change in sebum production after probiotic supplementation. Secondary outcomes included changes in gut microbiome, skin biophysical properties, skin microbiome, and blood SCFAs.

Probiotic supplementation resulted in a 13% decreasing trend in facial sebum excretion rate (p = 0.18) overall. In participants with acne, this decrease was more pronounced (28%, p = 0.125). Skin hydration showed an increasing trend on the cheek with probiotic supplementation (p = 0.18). TEWL increased overall and in both acne and non-acne groups after probiotic supplementation. Baseline FABP-2 levels were higher in participants with acne (p = 0.088). Placebo did not significantly affect plasma markers, but probiotic supplementation normalized LPS levels increased by placebo in the acne group. In the acne group, placebo increased LPS levels (p < 0.05), while probiotics normalized them. Probiotic supplementation significantly reduced noninflammatory and total acne lesions, with inflammatory lesions showing an approaching significant decrease (p = 0.054). Shannon diversity of gut and skin microbiomes did not significantly change. However, in the non-acne group, probiotics increased Akkermansia, while in the acne group, probiotics increased Lachnospiraceae and Ruminococcus gnavus. Probiotic supplementation increased the acetate/propionate ratio significantly (p<0.05) overall, with an increasing trend in the non-acne group (p=0.05).

The study provides clinical evidence supporting the gut-skin axis, showing that spore-based probiotic supplementation modulates skin biophysical properties and sebum excretion, particularly in individuals with acne. The 37% reduction in total lesion count at 4 weeks aligns with a previous study showing a similar reduction. The improvements in acne lesions and a trend toward reduced sebum suggest that sebum modulation may contribute to acne improvement. The elevated baseline FABP-2 levels and their reduction trend after probiotic supplementation suggest improved gut permeability in acne participants. The normalization of LPS levels further supports this conclusion. While zonulin did not show significant changes, the variations in responses among LPS, FABP-2, and zonulin suggest the need for more comprehensive assessment of gut permeability. Changes in the gut microbiome, while not impacting overall diversity, revealed shifts in bacterial genera in both acne and non-acne groups, possibly linked to SCFA production and anti-inflammatory effects. The increase in TEWL after probiotic supplementation, without associated skin irritation, suggests a potential role of sebum in skin barrier function.

This pilot study demonstrates that spore-based probiotic supplementation can influence the gut microbiome and reduce sebum production, particularly in individuals with acne. Improvements in acne lesion counts and increased acetate/propionate ratios were observed. Future studies with larger sample sizes and longer durations are needed to confirm these findings and further investigate the mechanisms underlying the gut-skin axis modulation by probiotics.

This study had limitations, including a small sample size (particularly in the acne group), an assessment timeframe of only 4 weeks, and fecal sampling focusing primarily on the distal colon. The lack of dietary restrictions and the use of non-gold standard permeability markers (LPS, FABP-2, zonulin) are also acknowledged limitations. Future research should address these limitations through larger, longer studies and more robust measurements of gut permeability.