Background and Objectives: Acne vulgaris is a prevalent chronic inflammatory skin condition affecting adolescents and young adults worldwide. Increasing concern regarding antimicrobial resistance has renewed interest in microbiome-modulating therapies, including oral probiotics. This systematic review and meta-analysis evaluated the efficacy and safety of oral probiotic supplementation for acne vulgaris using contemporary random-effects methods. Materials and Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, and ClinicalTrials.gov through November 2025 without language restrictions. Eligible studies were double-blind randomized controlled trials (RCTs) comparing oral probiotics with placebo or standard therapy for ≥4 weeks and reporting quantitative acne severity outcomes. Risk of bias was assessed using RoB 2.0. Standardized mean differences (SMDs) were pooled using restricted maximum likelihood (REML) with Hartung–Knapp adjustment. Heterogeneity was summarized using I2, τ2 (95% CI), and 95% prediction intervals. Adverse events were extracted. Results: Three RCTs (n = 231) met eligibility criteria. Pooled analysis suggested a modest reduction in inflammatory lesion counts favoring probiotics (SMD −0.57; 95% CI −0.94 to −0.21), although heterogeneity was substantial (I2 = 72%; τ2 = 0.11). The 95% prediction interval (−1.25 to 0.11) indicated that future studies may plausibly observe no meaningful effect. Sensitivity analyses using the DerSimonian–Laird estimator produced comparable results. All trials reported good short-term tolerability with no serious adverse events. Risk of bias was low in two trials and of some concern in one. Certainty of evidence was rated low to moderate. Conclusions: Oral probiotics may modestly reduce acne severity as a generally safe, antibiotic-sparing adjunct; however, the current evidence base is small and heterogeneous, and the certainty of effect remains low-to-moderate. Larger, standardized RCTs are required before firm clinical recommendations can be made. Registration: PROSPERO CRD420251181388. Funding: This research received no external funding.
Tjiu et al. (Wed,) studied this question.