Prospective Placebo-Controlled Assessment of Spore-Based Probiotic Supplementation on Sebum Production, Skin Barrier Function, and Acne

Antibiotics are commonly used for inflammatory dermatologic conditions such as acne, rosacea, and hidradenitis suppurativa, but chronic use contributes to drug-resistant bacteria and gut dysbiosis. Interest has grown in the gut-skin axis, whereby gut microbes may influence cutaneous immune and inflammatory responses. The study aims to prospectively evaluate whether an oral spore-based probiotic can modulate skin biomechanical properties (sebum production, transepidermal water loss, and hydration), improve acne outcomes in noncystic acne, and alter the gut microbiome and circulating short-chain fatty acids, thereby informing potential mechanisms along the gut-skin axis.

Prior work suggests probiotics can exert anti-inflammatory effects locally and systemically. Clinical and preclinical studies have reported dermatologic benefits: probiotics may improve atopic dermatitis; a combination of Lactobacillus acidophilus, L. delbrueckii ssp. bulgaricus, and Bifidobacterium bifidum had efficacy comparable to minocycline 100 mg daily for acne; Bifidobacterium breve supplementation attenuated UV-induced decreases in skin hydration and increases in TEWL in mice, and B. breve-fermented milk improved skin hydration in humans. Fermented foods have also been associated with increased skin hydration. However, human studies are sparse regarding how probiotic supplementation affects sebum production and global skin barrier properties. This study addresses these gaps by examining spore-based probiotics and their effects on skin metrics, acne, the gut microbiome, and plasma SCFAs.

Design: Single-blinded, placebo-controlled, 8-week study (June–October 2018), IRB-approved (UC Davis, #1242039) and registered (NCT03605108). Twenty-five healthy adults (mean age 30.8 years; range 19–62), including 7 with noncystic acne, were enrolled. Exclusions: recent topical/systemic antibiotics or antifungals, benzoyl peroxide use, BMI >30 kg/m2, recent hormonal birth control changes, isotretinoin exposure, recent topical retinoid use, lipid-altering medications, smoking history, and cystic acne. Participants maintained stable facial regimens and avoided facial procedures. Intervention: All participants received placebo capsules for 4 weeks, then spore-based probiotics (Megasporebiotic; 4 billion spores/day from Bacillus indicus HU36, B. subtilis HU58, B. coagulans, B. licheniformis, B. clausii) for 4 weeks. Dosing: two capsules daily. Visits at baseline, week 4, and week 8. Participants avoided washing/applying products to the face on visit days. Assessments: High-resolution facial photography (BTBP 3D Clarity Pro) at each visit; acne lesion counts (inflammatory and noninflammatory) by a blinded board-certified dermatologist. Skin biophysical measures included sebum excretion rate (Sebumeter SM 815), TEWL (Vapometer), and hydration (MoistureMeterSC) on forehead and cheeks. Biospecimens: Fasting blood at each visit for SCFAs and markers of inflammation and intestinal permeability (TNF-α, LPS, FABP-2, zonulin). Plasma processed and stored at −80°C; ELISAs run in triplicate (FABP-2, TNF-α: Thermo Fisher; LPS, zonulin: MyBioSource). Microbiome: Skin swabs (nasolabial, glabellar) and fecal samples collected at each timepoint and stored at −80°C. DNA extraction with Qiagen PowerSoil kits; 16S rRNA V3–V4 amplification (Illumina MiSeq, 300-cycle paired-end). Data processed in Qiime2 with PCoA, Shannon diversity, t-tests, fold-changes, and Δ relative abundances; phylogenies constructed in MEGA7 when needed using type sequences from RDP. SCFA quantification: Plasma SCFAs derivatized (DiMTBS) and quantified by GC–MS with stable isotope internal standards; data processed with MassHunter. Statistics: Primary outcome was reduction in sebum production after 4 weeks of probiotic supplementation. Secondary outcomes included gut microbiome shifts, changes in skin barrier properties and skin microbiome, and blood SCFAs. Analyses conducted for overall cohort and stratified by acne status (Acne n=7; No Acne n=18). Repeated measures Wilcoxon test; alpha 0.05. P-values <0.05 considered significant; 0.05–0.2 reported as approaching significance. Prism v9 used.

• Sebum and skin properties: Placebo induced no change in sebum excretion. Probiotic supplementation showed a 13% decreasing trend in overall sebum excretion rate (p=0.18). In the acne group, sebum excretion decreased by 28% (p=0.125), with no change during placebo. Cheek skin hydration trended upward after probiotics (p=0.18); forehead hydration unchanged. TEWL increased on the cheek overall after probiotics and trended upward on the forehead (overall p=0.14; acne p=0.08); increases were observed on the cheek in both acne and no-acne groups, and on the forehead in the acne group.
• Gut permeability and inflammation markers: At baseline, FABP-2 was higher in acne vs no acne (p=0.088), while TNF-α, zonulin, and LPS showed no group differences. Placebo did not change FABP-2, zonulin, or TNF-α; LPS increased by 9.2% after placebo in the acne group (p<0.05). Probiotic exposure normalized LPS levels in acne; zonulin and TNF-α remained unchanged. Comparing acne vs no acne after probiotics: FABP-2 trended down (p=0.14), zonulin trended up (p=0.099) in acne. Within acne group after probiotics: no significant shifts in FABP-2, TNF-α, or LPS; zonulin trended up (p=0.052).
• Acne outcomes (n=7): Placebo led to no changes. Probiotics significantly reduced total and noninflammatory lesion counts; inflammatory lesion counts decreased and approached significance (p=0.054).
• Microbiome diversity: No significant changes in Shannon diversity for skin or gut microbiomes after placebo or probiotics in either group.
• Gut microbiome composition: No-acne group after probiotics showed large genus-level fold increases in Alloprevotella (42×), Lactococcus (18×), Rhodospirillales (11×), and Prevotella (9.7×). Largest relative abundance changes included increases in Akkermansia (2.8×) and Prevotellaceae NK3B31 group (2.9×), and decreases in Lactobacillus (−13×), Ruminococcus torques group (−3.5×), and Streptococcus (−12×). Acne group after probiotics showed increases in Selenomonadales (16×), Ruminococcus gnavus group (15×), and Erysipelatoclostridium (13×), with decreases in Ruminidostridium (−7.0×), Erysipelotrichaceae (−9.0×), Butyricicoccus (−8.6×), Ruminococcus (−10×), and Clostridium sensu stricto (−34×). Largest relative abundance changes included increases in Streptococcus (6.2×) and Ruminococcus gnavus group (15×), and a decrease in Veillonella (−5.3×).
• Plasma SCFAs: At baseline, acne group trended toward lower acetate (p=0.15), with no differences in propionate or butyrate. Probiotics led to an increasing trend in acetate overall (p=0.13) and a significant increase in the acetate/propionate ratio. In the no-acne group, acetate trended up (p=0.11) and the acetate/propionate ratio increased (p=0.05). In acne, the acetate/propionate ratio increased 2.6-fold but was not statistically significant (p=0.33).

Spore-based probiotic supplementation modulated skin biophysical properties, including a trend toward reduced sebum excretion and increased TEWL, and improved acne lesion counts within 4 weeks, aligning with prior probiotic acne studies. The concurrent trends in reduced sebum and improved acne suggest sebum modulation may contribute to clinical benefit. Biomarker changes support a gut-skin connection: in acne, LPS rose with placebo and normalized with probiotics, and FABP-2 was elevated at baseline with a tendency to decrease after probiotics, consistent with amelioration of intestinal permeability (“leaky gut”). Zonulin did not show parallel changes, highlighting variability among permeability markers and indicating the need for gold-standard assessments (e.g., lactulose/mannitol). Gut microbiome shifts occurred without changes in alpha diversity, with increases in SCFA-associated taxa (Akkermansia, Prevotella in no-acne; Lachnospiraceae/Ruminococcus gnavus in acne). Circulating SCFAs reflected these shifts, with increased acetate and acetate/propionate ratio after probiotics, particularly notable in effect size within the acne group. Together, these findings suggest that spore-based probiotics may influence acne and skin physiology via modulation of gut microbiota and SCFA profiles, potentially impacting intestinal barrier function and systemic inflammation. Increased TEWL without clinical dryness might reflect reduced sebum contributions to barrier measurements rather than barrier damage.

Spore-based probiotic supplementation shifted the gut microbiome, increased circulating acetate and the acetate/propionate ratio, and trended toward decreased sebum production, with significant improvements in total and noninflammatory acne lesions after 4 weeks in participants with noncystic acne. Taxonomic shifts included increases in Akkermansia in participants without acne and increases in Lachnospiraceae and Ruminococcus gnavus in those with acne. These findings support further investigation of spore-based probiotics over longer durations (8–12 weeks) to clarify effects on SCFAs (especially acetate), facial sebum production, skin barrier measures, and acne outcomes.

Pilot study with a small acne subgroup (n=7), limiting statistical power. Fecal sampling primarily reflects distal colonic microbiota and may not capture small intestinal or proximal colonic communities. Supplementation period was short (4 weeks), whereas acne trials often span 8–12 weeks. No dietary restrictions were imposed, potentially introducing variability, although each participant served as their own control. Permeability biomarkers (LPS, FABP-2, zonulin) are convenient but not gold-standard measures of intestinal permeability.