Microbiome-Targeted Therapies for Acne Management: A Patient-Centric Evidence Review

1. Introduction

Acne vulgaris, a chronic inflammatory disorder of the pilosebaceous unit, affects nearly all individuals aged 15–17 years, with moderate to severe forms impacting 15–20% of the population (Zaenglein et al., 2016). Beyond physical manifestations—comedones, papules, pustules, nodules, cysts, scarring, and dyspigmentation—acne significantly impairs psychosocial well-being and quality of life (QoL), with psychological effects comparable to chronic conditions like asthma or diabetes (Vallerand et al., 2018). Severe cases are associated with increased risks of depression and suicidal ideation (Halvorsen et al., 2011).

Historically, acne pathogenesis was attributed to androgen-driven sebaceous gland hyperactivity, follicular hyperkeratosis, and inflammation mediated by Cutibacterium acnes (formerly Propionibacterium acnes) (Dréno et al., 2018). Recent research, however, emphasizes skin microbiome dysbiosis, recognizing C. acnes as a commensal bacterium with specific pathogenic strains (Fitz-Gibbon et al., 2013). This ecological perspective highlights the role of microbial diversity and interactions in acne, advocating for therapies that selectively modulate pathogenic strains while preserving beneficial ones (O’Neill & Gallo, 2018). The „gut-skin axis” further links gut dysbiosis to skin inflammation via immune, endocrine, and metabolic pathways, with short-chain fatty acids (SCFAs) from gut bacteria reducing systemic inflammation (Bowe & Logan, 2011; Salem et al., 2018).

Conventional treatments, including antibiotics, benzoyl peroxide (BPO), retinoids, and isotretinoin, are effective but limited by side effects (e.g., irritation, photosensitivity), antibiotic resistance, and poor adherence (Eichenfield et al., 2021). Antibiotic resistance, driven by overuse, diminishes treatment efficacy, necessitating alternative strategies (Walsh et al., 2016). Patient-centric outcomes, such as QoL and treatment satisfaction, are critical, as side effects and dissatisfaction often lead to discontinuation (Layton et al., 2017).

This review synthesizes recent evidence on microbiome-targeted therapies for acne, focusing on patient-centric outcomes. It aims to:

• Elucidate the skin microbiome’s role in acne pathogenesis.
• Evaluate conventional therapies’ impact on the cutaneous microbiome.
• Assess emerging microbiome-targeted strategies (probiotics, prebiotics, synbiotics, bacteriophage therapy).
• Analyze patient-reported outcomes (PROMs), QoL, satisfaction, and adverse events.
• Identify research gaps and propose future directions for personalized acne management.

2. Methodology

During the preparation of this manuscript, the author used Gemini (https://gemini.google.com/) and Grok (https://grok.com/) to collect information and write articles. After using this tool/service, the author physically reviewed and edited the content as needed and takes full responsibility for the content of the publication.

A systematic literature search was conducted across PubMed, Scopus, and Cochrane Library, targeting articles from January 1, 2014, to May 28, 2025. Keywords and Medical Subject Headings (MeSH) included: „acne vulgaris,” „skin microbiome,” „gut microbiome,” „probiotics,” „prebiotics,” „synbiotics,” „bacteriophage therapy,” „topical microbiome modulation,” „patient-reported outcomes,” „quality of life,” „patient satisfaction,” and „adverse events.”

Randomized controlled trials (RCTs) and well-designed clinical studies evaluating microbiome-targeted therapies for acne and reporting patient-centric outcomes (QoL, PROMs, satisfaction, adverse events) were prioritized. Articles from peer-reviewed journals or conference proceedings were included; non-peer-reviewed sources, opinion pieces, or studies unrelated to acne or microbiome modulation were excluded. Foundational papers predating 2014 were included only for historical context.

Data were extracted on study design, participant demographics, interventions, clinical efficacy, microbiological changes, PROMs, adverse events, and discontinuation rates. Findings were synthesized thematically, categorizing therapies, mechanisms, and outcomes.

Challenges include methodological heterogeneity in microbiome analysis (e.g., 16S rRNA vs. whole-metagenome sequencing), taxonomic resolution, clinical outcome measures (e.g., Investigator Global Assessment [IGA] scales), and PROMs, hindering meta-analyses (Ramrakha et al., 2021). The Acne Core Outcomes Research Network (ACORN) advocates for standardized outcome sets to address this (Layton et al., 2021). Limited long-term longitudinal studies also restrict insights into microbiome stability and sustained efficacy (Xu & Li, 2019).

3. Findings

3.1. The Evolving Role of the Skin Microbiome in Acne Pathogenesis

Acne pathogenesis involves dysbiosis within the pilosebaceous unit, beyond C. acnes proliferation (Dréno et al., 2018).

Strain Variability and Microbial Diversity: C. acnes phylotypes differ in pathogenicity; ribotype RT6 is associated with healthy skin, while RT4, RT5, RT8, and RT10 form biofilms and pro-inflammatory enzymes, exacerbating acne (Fitz-Gibbon et al., 2013). Acne-prone skin shows reduced microbial diversity, emphasizing the need for therapies that enhance beneficial strains (O’Neill & Gallo, 2018).

Role of Other Commensal Microbes: Staphylococcus epidermidis and S. capitis (e.g., strain E12) inhibit C. acnes via antimicrobial peptides (e.g., phenol-soluble modulins) and bacteriocins (Cogen et al., 2010). Fungi like Malassezia, prevalent in sebaceous areas, may contribute to acne via lipase activity, particularly in refractory cases (Sugita et al., 2015).

The Gut-Skin Axis: Gut dysbiosis influences skin inflammation through immune and metabolic pathways (Bowe & Logan, 2011). SCFAs from gut bacteria reduce intestinal permeability and pro-inflammatory markers, impacting skin health (Salem et al., 2018).

3.2. Impact of Conventional Acne Therapies on the Cutaneous Microbiome

Conventional treatments modulate the microbiome, often with unintended effects (Chien et al., 2019).

• Antibiotics (e.g., Doxycycline): Reduce C. acnes prevalence and increase alpha diversity, but promote antibiotic resistance and disrupt gut/skin microbiomes (Adler et al., 2017).
• Benzoyl Peroxide (BPO): Decreases C. acnes and alpha diversity, sometimes increasing S. aureus (Leyden et al., 2014).
• Isotretinoin: Reduces antibiotic-resistant C. acnes and normalizes microbiome diversity by lowering sebum production (Ryan-Kewley et al., 2017).
• Supramolecular Salicylic Acid (SSA): Increases microbial diversity and reduces pro-inflammatory markers (e.g., IL-1α, IL-6) (Yang et al., 2020).
• Aminolevulinic Acid-Photodynamic Therapy (ALA-PDT): Decreases Corynebacterium and Cutibacterium, increasing alpha diversity (Tao et al., 2018).

3.3. Emerging Microbiome-Targeted Therapeutic Strategies

Microbiome-targeted therapies address antibiotic resistance and dysbiosis through diverse mechanisms (Goodarzi et al., 2024).

Probiotics: Oral and Topical Applications

• Oral Probiotics: A 12-week RCT showed Lacticaseibacillus rhamnosus (CECT 30031) and Arthrospira platensis improved Acne Global Severity Scale and reduced non-inflammatory lesions (Fabbrocini et al., 2023). Combinations of Lactobacillus acidophilus, L. delbrueckii bulgaricus, and Bifidobacterium bifidum reduced lesion counts by 67% (Kim et al., 2019). Probiotics with doxycycline enhanced outcomes without side effects (Jung et al., 2024). Mechanisms include pathogen inhibition, immunomodulation (e.g., IL-8 suppression), and improved barrier function (Goodarzi et al., 2020).
• Topical Probiotics: Lactobacillus plantarum-GMNL6 cream improved skin, enhanced collagen synthesis, and suppressed C. acnes/S. aureus (Tsai et al., 2021). Enterococcus faecalis CBT SL-5 lotion reduced acne severity (Kang et al., 2019). A topical emulsion with Umbelliferae extract increased beneficial C. acnes RT6 and reduced pathogenic RT1–RT5, lowering IGA scores by 63% (Dall’Oglio et al., 2024).

Prebiotics and Synbiotics

• Prebiotics: Fructooligosaccharides (FOS) and galactooligosaccharides (GOS) increased Bifidobacterium and Lactobacillus, improving metabolic parameters and bacterial diversity (Moro et al., 2018).
• Synbiotics: An 8-week RCT showed a synbiotic with herbs reduced lesion counts, increased beneficial bacteria (e.g., Faecalibacterium prausnitzii), and elevated SCFAs (Rahmayani et al., 2024). Synbiotics inhibit biofilms and produce bacteriocins (Goodarzi et al., 2023).

Bacteriophage Therapy

Phages selectively lyse pathogenic C. acnes, reducing bacterial load and inflammation in preclinical models (Liu et al., 2022). Combined with antibiotics, phages may overcome resistance, but clinical trials are needed (Brown et al., 2024).

Table 1. Overview of Key Microbiome-Targeted Therapies for Acne.

Therapy Category	Specific Agents/Strains	Proposed Mechanisms	Key Clinical Outcomes	Reported Adverse Events/Safety
Probiotics (Oral)	Lacticaseibacillus rhamnosus (CECT 30031) + Arthrospira platensis; Lactobacillus acidophilus, L. delbrueckii bulgaricus, Bifidobacterium bifidum	Restores gut/skin microbiome homeostasis, produces antibacterial proteins/bacteriocins, immunomodulation (IL-8 inhibition), improves skin barrier, reduces inflammation	Significant improvement in Acne Global Severity Scale, reduced lesions (up to 67%), enhanced doxycycline outcomes	Well-tolerated, no reported side effects
Probiotics (Topical)	Lactobacillus plantarum-GMNL6; Enterococcus faecalis CBT SL-5; Umbelliferae extract + polysaccharide	Inhibits pathogenic strains, enhances collagen synthesis, increases beneficial C. acnes RT6, reduces inflammatory mediators	63% reduction in IGA score, decreased inflammatory lesions, improved barrier function	Favorable safety profile, lower irritation
Prebiotics	Fructooligosaccharides (FOS), Galactooligosaccharides (GOS)	Stimulates beneficial gut bacteria, increases diversity, promotes butyrate-producing microbes	Improved metabolic parameters, increased beneficial bacteria	Minimal side effects
Synbiotics	Bifidobacterium breve, Lacticaseibacillus casei, Ligilactobacillus salivarius + botanical extracts	Enhances beneficial microorganisms, inhibits biofilms, augments SCFAs	Reduced lesion counts, improved gut health, increased SCFAs	Well-tolerated
Bacteriophage Therapy	C. acnes phages	Selective lysis of pathogenic C. acnes, reduces inflammation	Reduced bacterial load/inflammation (preclinical)	Clinical safety data pending

Table 1. Overview of Key Microbiome-Targeted Therapies for Acne.

Therapy Category	Specific Agents/Strains	Proposed Mechanisms	Key Clinical Outcomes	Reported Adverse Events/Safety
Probiotics (Oral)	Lacticaseibacillus rhamnosus (CECT 30031) + Arthrospira platensis; Lactobacillus acidophilus, L. delbrueckii bulgaricus, Bifidobacterium bifidum	Restores gut/skin microbiome homeostasis, produces antibacterial proteins/bacteriocins, immunomodulation (IL-8 inhibition), improves skin barrier, reduces inflammation	Significant improvement in Acne Global Severity Scale, reduced lesions (up to 67%), enhanced doxycycline outcomes	Well-tolerated, no reported side effects
Probiotics (Topical)	Lactobacillus plantarum-GMNL6; Enterococcus faecalis CBT SL-5; Umbelliferae extract + polysaccharide	Inhibits pathogenic strains, enhances collagen synthesis, increases beneficial C. acnes RT6, reduces inflammatory mediators	63% reduction in IGA score, decreased inflammatory lesions, improved barrier function	Favorable safety profile, lower irritation
Prebiotics	Fructooligosaccharides (FOS), Galactooligosaccharides (GOS)	Stimulates beneficial gut bacteria, increases diversity, promotes butyrate-producing microbes	Improved metabolic parameters, increased beneficial bacteria	Minimal side effects
Synbiotics	Bifidobacterium breve, Lacticaseibacillus casei, Ligilactobacillus salivarius + botanical extracts	Enhances beneficial microorganisms, inhibits biofilms, augments SCFAs	Reduced lesion counts, improved gut health, increased SCFAs	Well-tolerated
Bacteriophage Therapy	C. acnes phages	Selective lysis of pathogenic C. acnes, reduces inflammation	Reduced bacterial load/inflammation (preclinical)	Clinical safety data pending

3.4. Patient-Centric Evidence: Quality of Life, Patient-Reported Outcomes, and Adverse Events

Patient-centric outcomes are critical for treatment success, influencing adherence (Layton et al., 2017).

Quality of Life (QoL) and Psychosocial Impact: Acne impairs QoL, increasing risks of depression and social isolation (Vallerand et al., 2018). Effective treatments improve QoL and self-esteem (Smith et al., 2024). Positive health behaviors (e.g., physical activity) enhance QoL, while excessive screen time worsens mental health (Alotaibi et al., 2024).

Patient-Reported Outcome Measures (PROMs): PROMs like Acne-QoL, CompAQ, and Skindex-16 provide insights into patient experiences (Thiboutot et al., 2021). Heterogeneity in PROMs hinders standardization, necessitating validated measures (Ramrakha et al., 2021).

Table 2. Summary of Patient-Reported Outcome Measures (PROMs) in Acne Research.

PROM Name	Primary Domains Measured	Target Acne Location	Validity/Reliability Status	Key Strengths	Key Limitations/Challenges
Acne-QoL	Emotional well-being, social function, symptom bother, self-perception	Facial acne	Validated, good consistency (0.77–0.96), ICC 0.84–0.90	Widely used, acne-specific	Limited to facial acne, fixed time frames
CompAQ	Emotional well-being, social function, symptom bother, appearance, treatment concerns	Facial/truncal acne	Good consistency (0.74–0.96), ICC 0.88–0.97, not externally validated	Covers facial/truncal acne	Lacks external validation, layout issues
Skindex-16	Symptoms, emotions, functioning	General skin	Good consistency (0.74–0.96), ICC 0.88–0.97	Shorter, reduces burden	Not acne-specific, limited validation

Table 2. Summary of Patient-Reported Outcome Measures (PROMs) in Acne Research.

PROM Name	Primary Domains Measured	Target Acne Location	Validity/Reliability Status	Key Strengths	Key Limitations/Challenges
Acne-QoL	Emotional well-being, social function, symptom bother, self-perception	Facial acne	Validated, good consistency (0.77–0.96), ICC 0.84–0.90	Widely used, acne-specific	Limited to facial acne, fixed time frames
CompAQ	Emotional well-being, social function, symptom bother, appearance, treatment concerns	Facial/truncal acne	Good consistency (0.74–0.96), ICC 0.88–0.97, not externally validated	Covers facial/truncal acne	Lacks external validation, layout issues
Skindex-16	Symptoms, emotions, functioning	General skin	Good consistency (0.74–0.96), ICC 0.88–0.97	Shorter, reduces burden	Not acne-specific, limited validation

Adverse Events (AEs) and Treatment Adherence: Topical agents cause mild irritation (e.g., erythema, scaling), with BPO and retinoids most irritative (Zaenglein et al., 2016). Oral antibiotics risk resistance and gut dysbiosis (Adler et al., 2017). Discontinuation rates are high due to unresponsiveness (62.3%) or side effects (37.7%) (Schnopp et al., 2019). Probiotics and synbiotics show fewer AEs, enhancing adherence (Fabbrocini et al., 2023; Rahmayani et al., 2024).

Table 3. Reported Adverse Events and Discontinuation Rates of Acne Therapies.

Therapy Type	Common Adverse Events	Discontinuation Rate	Primary Reasons	Adherence Notes
Topical Retinoids	Irritation, photosensitivity	40%	Side effects (50%), no response (50%)	High irritative potential
Benzoyl Peroxide	Irritation, stinging	44.1%	Side effects (33.3%), no response (66.7%)	Increases S. aureus
Oral Antibiotics	Gut dysbiosis, resistance	53.3%	No response (87.5%), side effects (12.5%)	Resistance concerns
Oral Probiotics	Rare	Low	High tolerability	Enhances routine treatments
Topical Probiotics	Mild irritation	Low	High tolerability	Significant improvement
Synbiotics	Rare	Low	High tolerability	Improved gut health

Table 3. Reported Adverse Events and Discontinuation Rates of Acne Therapies.

Therapy Type	Common Adverse Events	Discontinuation Rate	Primary Reasons	Adherence Notes
Topical Retinoids	Irritation, photosensitivity	40%	Side effects (50%), no response (50%)	High irritative potential
Benzoyl Peroxide	Irritation, stinging	44.1%	Side effects (33.3%), no response (66.7%)	Increases S. aureus
Oral Antibiotics	Gut dysbiosis, resistance	53.3%	No response (87.5%), side effects (12.5%)	Resistance concerns
Oral Probiotics	Rare	Low	High tolerability	Enhances routine treatments
Topical Probiotics	Mild irritation	Low	High tolerability	Significant improvement
Synbiotics	Rare	Low	High tolerability	Improved gut health

4. Discussion

Acne pathogenesis involves microbiome dysbiosis, with C. acnes strain variability and reduced diversity as key factors (Fitz-Gibbon et al., 2013). Conventional therapies disrupt beneficial microbiomes and drive resistance, except isotretinoin, which normalizes diversity (Ryan-Kewley et al., 2017). Microbiome-targeted therapies (probiotics, prebiotics, synbiotics, phages) restore balance, modulate immunity, and improve patient outcomes with fewer AEs (Goodarzi et al., 2024). PROMs and QoL are integral to success, directly impacting adherence (Layton et al., 2021).

Methodological heterogeneity in microbiome analysis and PROMs limits comparisons and meta-analyses (Ramrakha et al., 2021). Long-term studies are scarce, hindering insights into sustained efficacy (Xu & Li, 2019). Mechanisms of probiotic and prebiotic effects, roles of mycobiome/virome, and biomarkers for personalized therapy need further exploration (Goodarzi et al., 2020; Sugita et al., 2015).

Standardized protocols, as advocated by ACORN, are essential (Layton et al., 2021). Large-scale RCTs with extended follow-up are needed to validate microbiome-targeted therapies (Fabbrocini et al., 2023). Biomarkers (e.g., microbial profiles, metabolomic signatures) will enable personalized approaches (O’Neill & Gallo, 2018). Combining therapies or integrating digital health tools (e.g., telemedicine, apps) could enhance efficacy and adherence (Smith et al., 2024). Ethical considerations, such as preserving microbial diversity and combating resistance, underscore the need for targeted therapies (Brown et al., 2024).

5. Conclusion

Microbiome-targeted therapies mark a transformative shift in acne management, addressing dysbiosis and patient well-being with favorable safety profiles. Probiotics, prebiotics, synbiotics, and bacteriophage therapy offer sustainable alternatives to conventional treatments, though standardization and longitudinal data are needed. Future research should focus on biomarkers, combination therapies, and digital health to achieve personalized, patient-centric care, improving clinical outcomes and QoL.