Role of Probiotics in Managing Acne Vulgaris: A Systematic Review and Meta-Analysis of Clinical Trials

Abstract

Background:

Dysregulation of the skin microbiome is implicated in acne pathogenesis.

Objective:

To evaluate the efficacy of probiotics in the management of acne.

Methods:

Searches were conducted in 3 databases through June 30, 2024. Clinical trials that compared probiotics with controls and investigated their efficacy in acne were included. Primary outcomes were standardized mean differences (SMDs) for the change from baseline to posttreatment in total lesion count (TLC), noninflammatory lesion count (NILC), and inflammatory lesion count (ILC). Secondary outcomes included Global Acne Grading System (GAGS) scores, Investigator’s Global Assessment, erythema, and sebum levels.

Results:

Thirteen studies comprising 18 study arms and 1453 participants were included. There were no significant reductions in TLC (SMD, −0.22; 95% confidence interval [CI]: −0.50 to 0.07; I² = 75%), NILC (SMD, −0.20; 95% CI: −0.48 to 0.08; I² = 72%), or ILC (SMD, −0.13; 95% CI: −0.34 to 0.09; I² = 52%) with probiotics compared with controls. However, oral probiotics were associated with a significant reduction in GAGS scores (SMD, −0.47; 95% CI: −0.81 to −0.13; I² = 67%) versus controls. Subgroup analyses indicated that this effect was most prominent in mild-to-moderate acne patients who received oral probiotics containing Lactobacillus species combined with other strains for a minimum of 12 weeks.

Conclusions:

Probiotics did not demonstrate a significant reduction in acne lesion counts. However, they were associated with improvements in acne severity as measured by GAGS scores. These findings should be interpreted with caution given the heterogeneity across studies and the fluctuating natural course of acne.

Introduction

Acne vulgaris (AV) is a chronic inflammatory disorder of the pilosebaceous unit. Its pathogenesis involves follicular hyperkeratinization, hormonal effects on sebum, inflammation, and Propionibacterium acnes (subsequently Cutibacterium acnes [C. acnes]). ¹ Previously, C. acnes was believed to be the sole microbial cause of acne, leading to the widespread use of antibiotics as a treatment. However, recent evidence indicates that various subtypes of C. acnes contribute to the development of acne. ² Imbalances between C. acnes phylotypes or between C. acnes and other skin microbes, particularly Staphylococcus epidermidis (S. epidermidis), may trigger acne. ² Additionally, gut microbiota also play a role via the gut-skin axis, where increased intestinal permeability allows microbial metabolites to affect the skin microbiome. ³

A recent systematic review on the cutaneous microbiome in acne highlighted 3 main contributors: C. acnes, S. epidermidis, and reduced skin microbiome diversity. ⁴ Given these insights, probiotics—administered alone or alongside standard therapies—have shown promise in acne management, though larger, high-quality randomized controlled trials (RCTs) are still needed.^5,6 Despite these findings, current treatment guidelines for AV do not include any recommendations regarding probiotics.^{7 -10} An earlier systematic review summarized potential benefits but lacked a meta-analysis. ⁵

We therefore conducted a systematic review and meta-analysis to evaluate the efficacy of probiotics in managing AV.

Materials and Methods

Literature Search and Selection Criteria

This systematic review and meta-analysis was conducted in accordance with standardized procedures and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.^11,12 The study protocol was registered in PROSPERO, an international database for prospectively registered systematic reviews in health and social care (CRD42024580125). Relevant studies were searched in electronic databases including the Cochrane Library, MEDLINE (via PubMed), and Scopus (via ELSEVIER), up to June 30, 2024, with English language. Search terms and strategies, primarily based on interventions, are detailed in Supplementary Data S1. Google scholar and citation searching were also searched to cover all grey literature.

Eligibility Criteria

Two authors (N.J. and C.U.) independently screened studies using predefined eligibility criteria. Studies were included if they were clinical trials (randomized or non-randomized) involving participants with AV aged >7 years and compared oral or topical probiotics for ≥1 week against placebo or active controls. The 1 week treatment threshold was chosen as the shortest period likely to yield measurable probiotic benefits. ¹³ Primary outcomes included objective measures—total lesion count (TLC), noninflammatory lesion count (NILC), and inflammatory lesion count (ILC). Secondary outcomes included subjective assessments such as Global Acne Grading System (GAGS), proportion of patients achieving Investigators’ Global Assessment (IGA) scores of 0 or 1, erythema, and sebum production. Discrepancies were resolved by consensus with a third author (S.C.). Exclusion criteria were nonhuman studies, studies on postbiotics, studies on skin diseases other than AV, and single-arm studies. For duplicate reports, the most recent and largest sample size was used.

Data Extraction

Two authors (N.J. and C.U.) independently extracted key data from each clinical trial, including first author, sample size, country, year, study design, patient characteristics, acne severity, site, mean age, probiotic dosage and form, treatment duration, control type, specified outcomes, and conflicts of interest. Two reviewers then independently evaluated full texts of potentially eligible studies, resolving disagreements by consensus.

TLC data were extracted, with noninflammatory lesions defined as comedones and inflammatory lesions as papules, pustules, or nodules. Reductions in TLC, NILC, and ILC before and after treatment were recorded for both the probiotic and control groups. Acne severity was assessed using GAGS and IGA.^14,15 For IGA, the proportion of patients achieving scores of 0 (clear) or 1 (almost clear) was used as the primary success outcome. Data on erythema and sebum levels were also extracted for pooled analysis.

Quality Assessment

Two authors conducted the quality assessments independently and reached a consensus with the third author in case of any disagreements. The quality of individual RCTs was evaluated with the version 2 of the Cochrane risk-of-bias (ROB) tool for randomized trials (RoB 2).^16,17 The Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool was used for assessing the ROB in non-randomized studies of interventions. ¹⁸

Data Analysis

Standardized mean differences (SMD) were calculated to compare pretreatment and posttreatment effects between the probiotic and control groups for outcomes including reductions in TLC, NILC, ILC, GAGS scores, erythema, and sebum production. Dichotomous outcomes were expressed as relative risk (RR) with 95% confidence intervals (CIs) for the proportion of patients achieving IGA scores of 0 or 1. A random-effects model was applied when heterogeneity was present; otherwise, a fixed-effects model was used. Effect sizes and 95% CIs were derived using the inverse variance method. Heterogeneity was assessed with Cochran’s Q test and Higgins’ I² statistic, defined as significant when P < .1 or I² ≥ 50%.^19,20

Subgroup analyses were performed by acne severity, probiotic form, treatment duration, use as monotherapy or combination, probiotic type, control type, trial design, and geographic location. Sensitivity analyses assessed robustness by excluding studies with high ROB or small-study effects, using leave-one-out cross-validation. Publication bias was evaluated by funnel plot and Egger’s test. All analyses were conducted using SPSS 29.0.2.0 (IBM Corp., Armonk, NY, USA) and Review Manager (RevMan 5.4.1; The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).^21,22

Results

After removing duplicate records, a total of 222 studies remained. A screening of the abstracts and titles resulted in the inclusion of 17 studies. After evaluating the full texts, 5 studies were excluded,^{23 -27} leaving 12 eligible studies. Additionally, 1 study was identified via Google Scholar, ²⁸ bringing the total number of included studies to 13. Among these, 11 RCTs and 2 were non-RCTs, comprising a total of 18 study arms^{28 -40} (Figure 1).

Figure 1.

PRISMA 2020 flow diagram for new systematic reviews, which included searches of databases, registers and other sources. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Characteristics of Included Studies

Among the 13 studies, a total of 1453 participants were enrolled, studies assessed the efficacy of oral probiotics with 500 participants and 3 studies with 269 participants receiving topical probiotics. The characteristics of the included studies are summarized in Table 1. The studies predominantly involved patients diagnosed with mild-to-moderate AV, except for 1 study that included patients with severe AV. ³⁵

Table 1.

Characteristics of the Included Studies With Oral and Topical Probiotic Treatment of Acne Vulgaris.

No	Author (y)	Country	Register number	Type of study	Type of patients	Location	n (I/C)	Percentage of female (I/C)	Mean age (I/C)	Type (dose in CFU) of probiotics	Type of control and dose	Duration (wk)	COI
Oral probiotics
1	Eguren (2024)	Spain	NCT04570319	RCT	Mild AV according to AGSS	Face and extrafacial lesion	42/39	76.19/61.54	20.13/18.03	Lacticaseibacillus rhamnosus CECT 30031, Arthrospira platensis BEA_IDA_0074B (1 × 109)	Placebo	12	Yes a
2	Liang (2024)	China	ChiCTR2200063499	RCT (open label)	20-50 TLC achieved grades III (pustules)-IV (nodules, cysts) of the Chinese Acne Treatment Guidelines with >10 ILCs	Face	30/30	57.1/51.4	21.72/22.68	L. plantarum MH-301 (2 × 109)	Isotretinoin	12	No
							30/30	60/51.4	22.44/22.68	L. plantarum MH-301 (2 × 109) and isotretinoin	Isotretinoin
3	Rybak (2023)	USA	NCT03605108	Prospective placebo-controlled (self-control)	Non-cystic acne	Face	7/7	NA	30.8	B. licheniformis, B. indicus, B. subtilis, B. clausii, and B. coagulans (2 × 109)	Placebo	4	Yes b
4	Irshad (2023)	Pakistan	NCT05629468	Quasi-experimental study	Mild-to-moderate AV	NA	25/25	NA	23 ± 5	L. acidophilus, L. rhamnosus, B. lactis, and B. bifidum (8 × 109) + azithromycin 250 mg/d EOD + topical 4% BP	Azithromycin 250 mg EOD + topical 4% BP	12	No
							25/25	NA	23 ± 5	L. acidophilus, L. rhamnosus, B. lactis, and B. bifidum (8 × 109) + topical 4% BP	Azithromycin 250 mg EOD + topical 4% BP
5	Rocha (2023)	Brazil	CAAE: 03728318.5.0000.5514	RCT	Mild-to-moderate AV according to IGA	Face	107/105	61.7/60.9	17	L. acidophilus NCFM (1 × 109), B. lactis HN019 (1 × 109), vitamins, and minerals with first 90 d of topical 0.1% adapalene and topical 2.5% BP	Placebo with first 90 d of topical 0.1% adapalene and topical 2.5% BP	26	Yes c
6	Rinaldi (2022)	Italy	Ethical Committee for Clinical Investigation of Genoa, Italy	RCT	Mild-to-moderate AV according to GAGS	Face and back	30/29	47/48	23.5/23.4	B. breve BR03 DSM 16604 (0.5 × 109), Lacticaseibacillus casei LC03 DSM 27537 (0.5 × 109), Ligilactobacillus salivarius LS03 DSM 22776 (1 × 109) + botanical extract (lupeol from Solanum melongena L. and Echinacea extract)	Botanical extract (lupeol from S. melongena L. and Echinacea extract)	8	Yes d
							27/28	52/43	23.4/23.7	B. breve BR03 DSM 16604 (0.5 × 109), L. casei LC03 DSM 27537 (0.5 × 109), L. salivarius LS03 DSM 22776 (1 × 109)	Placebo
7	Kim (2021)	Korea	KCT0005401	RCT	Mild-to-moderate AV according to IGA	Face	14/14	50/64.2	24.29/23.86	L. plantarum CJLP55 (10 × 109)	Placebo	12	Yes e
8	Tolino (2018)	Italy	NA	RCT	Mild-to-moderate AV according to GAGS	Face and back	60/60	100/100	25	L. acidophilus SGL11, L. casei SGL15, L. plantarum SGL07, S. thermophilus SGSt01 + topical SA	Placebo + topical salicylic acid	12	No
							60/60	0/0		L. acidophilus SGL11, L. casei SGL15, L. plantarum SGL07, S. thermophilus SGSt01 + topical SA	Placebo + topical salicylic acid
9	Kitkuakosol (2018)	Thailand	No. 005/60	RCT	Mild to moderate	Face	13/12	100/100	29.2/27.8	Actobacillus acidophilus, L. casei, B. longum, B. infantis, B. bifidum, L. lactis (100 × 109), Oligosaccharide (prebiotics) + 2.5% BP and 1% clindamycin lotion	Placebo + 2.5% BP and 1% clindamycin lotion	12	NA
10	Jung (2013)	Canada	Health Research Ethics Board	RCT (open label)	Mild-to-moderate according to Global Acne Assessment Scale	Face	15/15	100/100	NA	L. acidophilus (5 × 109), L. bulgaricus (5 × 109), B. bifidum (20 × 109) bid	Minocycline	12	No
							15/15	100/100	NA	L. acidophilus (5 × 109), L. bulgaricus (5 × 109), B. bifidum (20 × 109) bid + minocycline	Minocycline
Topical probiotics
11	Craft (2022)	USA	NCT02832063	RCT (phase IIb/III)	Mild-to-moderate AV with IGA	Face	181/179	52.5/51.4	NA	Nitrosomonas eutropha B244 (4 × 109 cells/mL and 4 pumps of spray to saturate the entire face applied bid)	Placebo	12	NA
12	Sathikulpakdee (2022)	Thailand	SWUEC-339/2562F	RCT	Mild-to-moderate of Leeds-revised criteria	Face	52/52	76.9/80.8	22.2/22.0	L. paracasei MSMC 39-1	2.5% BP	4	No
13	Lebeer (2022)	Belgium	NCT04216160	RCT (open label)	Mild to moderate	Face	36/31	60/64.1	17/18	L. rhamnosus GG, L. plantarum WCFS1, L. pentosus KCA1 (1 g)	Placebo	8	Yes f

Abbreviations: AGSS, Acne Global Severity Scale; AV, acne vulgaris; B. bifidum, Bifidobacterium bifidum; B. breve, Bifidobacterium breve; B. clausii, Bacillus clausii; B. coagulans, Bacillus coagulans; B. indicus, Bacillus indicus; B. infantis, Bifidobacterium infantis; B. lactis, Bifidobacterium lactis; B. licheniformis, Bacillus licheniformis; B. longum, Bifidobacterium longum; BP, benzoyl peroxide; B. subtilis, Bacillus subtilis; COI, conflict of interests; EOD, every-other day; GAGS, Global Acne Grading System; I/C, intervention/control; IGA, Investigator’s Global Assessment; ILC, inflammatory lesion counts; L. acidophilus, Lactobacillus acidophilus; L. bulgaricus, Lactobacillus bulgaricus; L. casei, Lacticaseibacillus casei; L. lactis, Lactococcus lactis; L. paracasei, Lacticaseibacillus paracasei; L. pentosus, Lacticaseibacillus pentosus; L. plantarum, Lacticaseibacillus plantarum; L. rhamnosus, Lacticaseibacillus rhamnosus; L. salivarius, Ligilactobacillus salivarius; NA, not available; RCT, randomized controlled trial; SA, salicylic acid; S. melongena, Solanum melongena; TLC, total lesion counts.

^aEN-D, PS-P, and VN-L are employees of Bioithas (a sister company of Bionou Research) and VN-L owns stock/stock options.

^bR.K.S. serves as a scientific adviser for LearnHealth, Arbonne, and Codex Labs and as a consultant to Burt’s Bees, Novozymes, Nutrafol, Abbvie, Sanofi, Fotona, Incyte, Leo, UCB, Novartis, Bristol Myers Squibb, Biogena, Lilly, Sun, and Regeneron Pharmaceuticals. J.M. serves as a consultant to Codex Labs. J.M. serves as a consultant for Codex Labs.

^cThe authors of the study act as speakers for the laboratory that financed the study—FARMOQUIMICA SA, Rio de Janeiro, Brazil.

^dFabio Rinaldi serve as a consultant for Giuliani S.p.A., Daniela Pinto, Laura Marotta, and Antonio Mascolo are employed by Giuliani S.p.A., Giammaria Giuliani is in the Board of Directors of Giuliani S.p.A., Marco Pane and Angela Amoruso have nothing to disclose.

^eHyun Sun Yun, Hee Yoon Ahn, and Ji Young Oh are employed by CJ Fooads R&D Center, CJ CheilJedang Corporation. L. plantarum CJLP55 (KCTC 11401BP, GenBank accession number GQ336971) was provided by CJ Foods R&D Center, CJ CheilJedang Corporation (Suwon, Republic of Korea). Other authors declare that there are no potential conflicts of interests with respect to the authorship and/or publication of this article.

^fYUN NV (www.yun.be) was funded as a biotech company focusing on probiotics for the skin after the scientific studies mentioned in this paper. I.C. and T.H. were employed at the University of Antwerp at the time of the study but are currently working at the R&D Department of YUN (www.yun.be). I.C. is now Chief Scientific Officer of YUN NV. T.H. is R&D manager of YUN NV. S.L. and J.L. are members of the Scientific Advisory Board of YUN NV. I.C., T.H., and S.L. are minority stakeholders of YUN. The PhD research of L.D. is currently funded by VLAIO through a Baekeland mandate in collaboration with YUN NV. Based on the data presented here, YUN NV has selected and formulated 3 Lactobacillus strains: L. pentosus YUN-V1.0, L. plantarum YUN-V2.0, and L. rhamnosus YUN-S1.0 in their commercial ACN product. Patents related to this work include dermatological preparations for maintaining and/or restoring healthy skin microbiota (WO2017220525A1) and preservation of microorganisms (WO2018002248). The remaining authors have no conflicts of interest to declare.

The probiotic spp. utilized in the studies included Lactobacillus spp. (n = 4), a combination of Lactobacillus, Bifidobacterium spp., and other spp. (n = 7), Bacillus spp. (n = 1), and Nitrosomonas eutropha (N. eutropha; n = 1), as detailed in Supplementary Table S1. The dosage of oral probiotics ranged from 0.5 × 10⁹ to 100 × 10⁹ CFU. The topical probiotics consisted of Lactobacillus spp. and N. eutropha.

The control groups across 18 study arms comprised placebo (n = 6), topical agents (n = 6), and oral agents (n = 6). The majority of the topical agents were standard acne medications, including clindamycin, benzoyl peroxide, salicylic acid, and adapalene. The oral agents included azithromycin, minocycline, and isotretinoin.

Quality of Included Studies

ROB assessment by RoB 2 for RCT and ROBINS-I for non-RCT are shown in Supplementary Tables S2 and S3, respectively.

Total Lesion Count

When comparing the SMD in the reduction of TLC before and after treatment, probiotics did not show a significant difference compared with the control group, with an SMD of −0.22 (95% CI: −0.50 to 0.07; I² = 75%), as illustrated in Figure 2a.

Figure 2.

Reduction in acne vulgaris lesion. (a) Total lesion count. (b) Noninflammatory lesion count. (c) Inflammatory lesion count.

A subgroup analysis of study arms involving participants with non-severe AV revealed a significant reduction in TLC, with SMD of −0.25 (95% CI: −0.47 to −0.02; I² = 55%). Further subgroup analysis indicated that study arms utilizing probiotics alone achieved a significant reduction in TLC, with SMD of −0.36 (95% CI: −0.65 to −0.07; I² = 71%; Supplementary Table S4).

Noninflammatory Lesion Count

Regarding the reduction in NILC before and after treatment, there was no statistically significant difference between the probiotic and control groups, with an SMD of −0.20 (95% CI: −0.48 to 0.08; I² = 72%), as illustrated in Figure 2b.

A subgroup analysis of study arms involving participants with non-severe AV revealed a significant reduction in NILC, with SMD of −0.32 (95% CI: −0.58 to −0.06; I² = 563%). A subgroup analysis of study arms that utilized combined types of probiotics revealed a significant reduction in NILC, with SMD of −0.65 (95% CI: −1.21 to −0.10; I² = 76%). Additionally, a subgroup analysis based on the geographical location of the study indicated that studies conducted in Asia reported a significant reduction in NILC, with SMD of −0.29 (95% CI: −0.57 to −0.00; I² = 68%).

Inflammatory Lesion Count

There was no statistically significant difference in the reduction of ILC between the probiotic and control groups, with an SMD of −0.13 (95% CI: −0.34 to 0.09; I² = 52%), as illustrated in Figure 2c.

Global Acne Grading System

In all included studies, specifically RCTs where GAGS was reported as an outcome, probiotics were administered in oral form to patients with non-severe AV. When comparing the change in GAGS scores from pretreatment to posttreatment, probiotics were associated with a significantly greater reduction compared with the control group, with an SMD of −0.47 (95% CI: −0.81 to −0.13; I² = 67%), as illustrated in Figure 3a.

Figure 3.

Reduction in severity of acne vulgaris. (a) GAGS. (b) IGA scores. GAGS, Global Acne Grading System; IGA, Investigators’ Global Assessment.

In subgroup analyses, study arms with treatment durations of 12 weeks or longer exhibited a significant reduction in GAGS scores, with an SMD of −0.62 (95% CI: −1.06 to −0.18; I² = 73%). Subgroup analyses of study arms utilizing probiotics alone also demonstrated a significant reduction in GAGS scores, with an SMD of −0.53 (95% CI: −0.91 to −0.15; I² = 69%). Additionally, subgroup analysis of study arms comparing probiotics to an active control indicated a significant reduction in GAGS scores, with an SMD of −0.64 (95% CI: −1.06 to −0.23; I² = 67%; Supplementary Table S4).

Investigators’ Global Assessment

When comparing the proportion of patients achieving an IGA score of 0 or 1, probiotics did not show a statistically significant difference compared with placebo, with a RR of 1.65 (95% CI: 0.48-5.62; I² = 89%), as depicted in Figure 3b.

Subgroup analyses indicated that study arms employing topical probiotics achieved a significant reduction in the IGA score to 0 or 1, with RR of 2.06 (95% CI: 1.07-3.97). Further subgroup analysis of study arms compared with placebo demonstrated a significant reduction on the IGA scale to 0 or 1, with RR of 2.15 (95% CI: 1.13-4.08; Supplementary Table S5).

Erythema

When evaluating the reduction in erythema based on SMD before and after treatment, there was no statistically significant difference between probiotics and the control, with an SMD of −0.17 (95% CI: −0.42 to 0.08; I² = 0%), as illustrated in Figure 4a.

Figure 4.

Reduction in other outcomes. (a) Erythema. (b) Skin sebum production.

^aErythema score measured by Mexameter MX18 scale with range 0 to 999, ²⁸ erythema score defined by 0 to 3, ³⁴ erythema index (a value) using a DSM III Colorimeter (Cortex Technology, Hadsund, Denmark) with range 0.0 to 99.9. ³²

^bSkin sebum measured by Sebumeter (SM815) range 0 to 350. ²⁸ (Kim et al., 2021). ³¹

Sebum Production

Upon comparing the reduction in sebum secretion through SMD from pretreatment to posttreatment, there was no statistically significant difference between probiotics and the control, with SMD of −28.34 (95% CI: −57.28 to 0.60; I² = 0%). This is depicted in Figure 4b.

Publication Bias

Funnel plots were generated to assess publication bias in outcomes, as shown in Supplementary Figure S1. Using funnel plots, there is no evidence of asymmetry in the interesting outcomes. Egger’s test indicated no significant publication bias, with P values of .255 for TLC, .240 for ILC, .188 for NILC, .050 for GAGS, .434 for IGA, and .640 for erythema.

Sensitivity Analyses

Sensitivity analyses were conducted by excluding studies with a high ROB and performing leave-one-out cross-validation by removing studies showing small-study effects (Supplementary Table S6). When the study with high ROB was excluded from the outcomes of TLC,^30,33,37 NILC,^33,37 ILC,^33,37 GAGS, ³⁶ IGA, ³³ no significant differences were observed across these outcomes except IGA with RR of 2.18 (95% CI: 1.15-4.12, I² = 0%).

In the leave-one-out cross-validation analysis, excluding a study with a high effect size and high variance from the funnel plots for outcomes of TLC, ³⁵ NILC, ³⁵ ILC, ³⁸ GAGS, ³⁴ IGA, ³³ erythema index, ²⁸ showed the robust effect in TLC (SMD −0.29, 95% CI: −0.52 to −0.07, I² = 58%), NILC (SMD −0.28, 95% CI: −0.52 to −0.03, I² = 61%), GAGS (SMD −0.52, 95% CI: −0.91 to −0.13, I² = 71%) and IGA reduction (RR 2.18, 95% CI: 1.15-4.12, I² = 0%) which favoured the probiotics arm.

Discussion

To our best knowledge, this is the first meta-analysis assessing both oral and topical probiotics in AV, which included current evidence. We also analyzed different outcomes assessment of both objective and subjective measurements. Our review suggested that oral probiotics significantly reduce the severity of AV, as assessed by GAGS, yielding SMD of −0.47 compared with the control. This effect is particularly pronounced in patients with mild-to-moderate acne who received oral probiotics for 12 weeks or longer. Although neither oral nor topical probiotics demonstrated a significant reduction in lesion count, the reported outcomes tended to favour the probiotics group.

An imbalance in the skin microbiome significantly impacts skin homeostasis, leading to dysbiosis and various skin conditions including acne. Current acne treatments can cause adverse effects that some patients find intolerable. Recently, pharmaceuticals, like probiotics, are gaining attention as alternative nonantibiotic treatments that can modulate dysbiosis and lower the risk of antimicrobial resistance. ⁴¹ Furthermore, it may enhance skin hydration, potentially alleviating irritation from topical acne treatments. ³¹

A previous systematic review presented a summary of individual studies and identified the potential roles of oral and topical probiotics in reducing lesion count, improving clinical assessments, modulating the skin microbiome, and positively influencing skin parameters. ⁵ Although direct comparisons with our meta-analysis are challenging due to differences in inclusion and exclusion criteria, our findings support a similar positive effect of probiotics on acne treatment. Specifically, probiotics were associated with a reduction in severity, particularly as measured by GAGS, with robust evidence of a statistically significant SMD compared with that in placebo. However, the most recent RCT evaluating the efficacy of oral probiotics compared oral doxycycline alone with oral doxycycline combined with probiotics containing 7 strains found no significant difference in GAGS scores between the 2 groups. Nevertheless, the combination therapy resulted in a greater reduction in acne severity, as assessed by the Global Acne Assessment Scale. ⁴²

Our study found that probiotic supplementation significantly reduced GAGS scores, with the greatest effect in patients with mild-to-moderate AV. Benefits were most evident in those receiving oral probiotics—particularly Lactobacillus spp. combined with other strains—for ≥12 weeks. The observed benefits in specific groups can be explained by several factors. In severe acne, probiotics alone may be insufficient to counter marked inflammation, which often requires systemic therapy such as isotretinoin, and microbiome modification may take longer to yield effects. ²⁴ These factors may help explain the positive outcomes observed in the subgroup with mild-to-moderate AV. It is important to note that this meta-analysis included only 1 study with participants suffering from severe acne. ³⁵ From subgroup analysis, probiotics also significantly reduced lesion counts in non-severe acne, with SMDs of −0.25 for TLC and −0.32 for NILC.

In the subgroup receiving oral probiotics, these supplements appear to exert systemic effects by modulating the gut-skin axis rather than by merely acting locally on the skin.^3,43 An imbalanced gut microbiome can lead to intestinal permeability issues, contributing to systemic inflammation and acne flares.^43,44 Probiotics potentially improve gut barrier function and modulate systemic immune responses.^38,45,46 In a murine model, supplements containing various Lactobacillus and Bifidobacterium strains have been shown to induce B and T cell hyporesponsiveness and downregulate T helper cell activity including T helper 1 and T helper 17 cells, which play a role in the inflammatory cascade associated with acne.^1,47 Probiotics may also have indirect influences on acne through body mass index reduction and psychological well-being enhancement.^{43,48 -50}

Regarding the group using a combination of Lactobacillus spp. and other probiotic strains, multiple species may enhance effectiveness by targeting diverse pathways in acne pathogenesis (Figure 5). Probiotics from the Lactobacillus and Bifidobacterium genera can modulate key mechanisms, including reducing pro-inflammatory cytokines such as IL-1α, which drives follicular hyperkeratinization and comedogenesis; blocking IL-1α has been linked to lower lesion counts and reduced anxiety.^51,52 Bifidobacterium lactis and certain Lactobacillus spp. can regulate sebum production by lowering insulin-like growth factor-1, increasing glucagon-like peptide-1, and improving insulin sensitivity, thereby limiting sebocyte proliferation. Lactobacillus rhamnosus also upregulates Forkhead Box O1, reducing lipogenesis and inflammation.^{3,53 -56} Certain microorganisms, such as Staphylococcus capitis and S. epidermidis, produce antimicrobial substances that suppress C. acnes growth.^57,58 Additionally, Streptococcus salivarius produces BLIS-like compounds, and enterocins from Enterococcus faecalis show antimicrobial activity against C. acnes, both associated with reduced inflammatory lesions.^59,60 Additionally, Lactobacillus spp. may suppress lipase activity, limiting nutrients available to C. acnes.^39,61

Figure 5.

Probiotics targeting various mechanisms of acne pathogenesis. Acne pathogenesis is primarily driven by 4 key mechanisms: follicular hyperkeratinization, hormonal influences on sebum production, inflammatory processes, and the colonization and activities of C. acnes. Certain probiotics, particularly those from the Lactobacillus and Bifidobacterium genera, exhibit various mechanisms to counteract acne pathogenesis. These probiotics can mitigate gut dysbiosis, which, if left unaddressed, increases intestinal permeability, leading to endotoxemia. Endotoxemia triggers inflammation and insulin resistance, thereby contributing to acne development. Probiotics can also downregulate T helper 1 and T helper 17 cells, which play a role in the inflammatory cascade associated with acne. Additionally, they may reduce levels of IL-1α, a cytokine that is crucial in the hyperkeratinization of the infundibular portion of the pilosebaceous unit, thereby contributing to comedogenesis. Bifidobacterium species specifically can decrease insulin resistance, which is linked to the hyperproliferation of sebocytes. Lactobacillus species can utilize IGF-1, which is associated with enhanced DHT response, consequently promoting lipogenesis in the sebaceous glands. Furthermore, many probiotics have the ability to inhibit the growth of C. acnes. Lactobacilli spp. might inhibit lipase activity, an enzyme that provides nutrition to C. acnes. Beyond these direct mechanisms, probiotics can also alleviate anxiety and depression, both of which are recognized triggers for acne. DHT, dihydrotestosterone; IGF-1, insulin-like growth factor-1; IL-1α, interleukin-1α.

Created in BioRender, Julanon (2025), https://BioRender.com/b34v137. C. acnes, Cutibacterium acnes.

For treatment durations ≥12 weeks, all studies in our meta-analysis reporting GAGS showed greater improvement with longer interventions.^29,34,36 We hypothesize that extending treatment beyond 12 weeks could provide additional benefits for acne management. However, interpretation should be cautious due to the variable, individualized nature of the hair follicle cycle. Serial video imaging has shown spontaneous changes in inflammatory lesions over just 4 days without treatment, ⁶² contributing to high placebo response rates—also observed in other follicular disorders like hidradenitis suppurativa. ⁶³ Well-designed RCTs incorporating active placebos are essential to validate treatment efficacy and reduce the risk of misinterpretation.

To the best of our knowledge, this study represents the first meta-analysis to examine the effects of probiotics in the management of AV. A key strength of our analysis lies in its comprehensive inclusion of both topical and oral probiotics, complemented by a predefined subgroup analysis.

Limitations in this study include the small number of studies, high heterogeneity from varied probiotic strains and baseline characteristics, and persistent variability despite subgroup analyses. The GAGS may underestimate disease severity in patients with high lesion counts or localized but extensive involvement, as regional grading is based solely on the most severe lesion type. Lastly, although GAGS reduction was statistically significant, the effect size was small. Larger double-blind RCTs of specific probiotic types with extended treatment periods are warranted.

Conclusion

Probiotics did not demonstrate a significant reduction in acne lesion counts. However, oral probiotics have been shown to reduce the severity of AV, as measured by the GAGS. They may serve as a therapeutic option for the management of mild-to-moderate AV, particularly when administered for at least 12 weeks.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.