Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

thank you for the important and valuable manuscript. The paper “ A Global Delphi Consensus on Acne and the Microbiome: Integrating International Expertise for Innovative Prevention and Therapeutic Strategies” is dedicated to an important issue on the role of human microbiota in acne pathogenesis and ways of preventing it. A global Delphi consensus format is well suited for such investigations and slows to attract multiple independent experts. However, the paper has certain drawbacks that require revisions. 

 

Major revisions

1. Conceptual mismatch: “microbiome” vs. Cutibacterium acnes-centric discussion

The manuscript consistently frames the topic around the “microbiome”; however, the discussion is predominantly focused on Cutibacterium acnes, with only limited and largely descriptive mention of other members of the skin microbiota (e.g., Staphylococcus epidermidis, Corynebacterium spp.).

The role of other taxa, including fungi (e.g., Malassezia), viruses (including bacteriophages as part of the microbial ecosystem), and interspecies interactions, are not explored in depth. As a result, there is a clear mismatch between the scope suggested by the title and section headings and the actual content.

The authors are encouraged to consider either:

• expanding the manuscript to include a broader and more balanced discussion of the skin microbiome and microbial community interactions in acne,
  
  or
  
  
• revising the title and section headings to more accurately reflect the primary focus on C. acnes.
  
  

Clarifying the scope is particularly important in a Delphi consensus context to avoid overgeneralisation.

2. The description of the modified Delphi process would benefit from greater methodological clarity to ensure transparency and reproducibility.

 

While the general workflow (literature review, iterative discussions, and survey rounds) is described, several key methodological aspects remain insufficiently detailed. Specifically, it is unclear:

• how many Delphi rounds were conducted,
  
  

• how the initial statements or questions were generated,
  
  

• how the questionnaires were structured,
  
  

• whether responses were anonymised,
  
  

• how disagreement or lack of consensus was managed,
  
  

• and how responses were quantitatively analysed.
  
  

 

Providing this information would strengthen the methodological rigor and allow readers to better assess the robustness of the consensus process.

3. Strength of consensus statements vs. level of evidence

Several consensus statements are presented with strong wording (e.g., regarding microbiome-targeted strategies for primary prevention or the benefits of prebiotics), despite the manuscript itself acknowledging that supporting clinical data remain limited.

While consensus reflects expert opinion, it does not equate to high-level evidence. The current framing may lead readers to overestimate the strength of the evidence base.

The manuscript would benefit from:

• more cautious wording of such statements,
  
  
• clearer differentiation between evidence-based conclusions and expert opinion,
  
  
• and explicit acknowledgment of areas where evidence is preliminary or lacking.
  
  

4. Potential influence of conflicts of interest on interpretation

Conflicts of interest are appropriately disclosed; however, the extent of industry involvement—particularly related to skincare and microbiome-targeted products—raises concerns about potential bias in the interpretation of evidence and the strength of certain recommendations.

The manuscript would benefit from a more cautious and balanced tone in these sectionsю Also, clearer separation of evidence-based conclusions from expert opinion and, where appropriate, explicit acknowledgment of limitations and uncertainties, are suggested.

5. Blurred boundary between narrative review and consensus

The manuscript combines elements of a narrative literature review with a Delphi consensus; however, the distinction between these components is not clearly defined.

There is no description of literature search strategy. Clarifying the role of the literature review (supportive vs. systematic) and distinguishing it from expert-derived consensus would improve the scientific rigor of the manuscript.

Minor Comments

1. All microbial taxa (genus and species names, e.g., Cutibacterium acnes, Staphylococcus epidermidis) should be consistently formatted in italics throughout the manuscript.
   
   
2. In line 210, reference “64” should be formatted as a superscript (in line with journal style).
3.  The figure is conceptually clear but appears largely schematic and not directly supported by specific data. Consider clarifying whether it represents a conceptual model and, if possible, linking elements more explicitly to referenced evidence. Also, the taxon names should be in italics.
   
   
4. The manuscript would benefit from a more balanced discussion, including limitations, conflicting findings, and areas of uncertainty, rather than predominantly highlighting “promising” or “beneficial” aspects.
   
   

Comments for author File: Comments.pdf

Author Response

Dear Reviewer,

Thank you very much for your insightful and constructive comments. We have carefully revised the manuscript accordingly and believe it has been significantly strengthened.

In response to your suggestions, we have expanded the discussion to better reflect the broader skin microbiome beyond Cutibacterium acnes, including other microbial taxa and interspecies interactions, while clarifying its central—but not exclusive—role in acne pathophysiology.

We have also improved the methodological transparency of the modified Delphi process by providing additional details regarding statement development, survey structure, anonymization, consensus thresholds, and handling of disagreement.

To address concerns regarding overinterpretation, we have revised the wording of several consensus statements to ensure a clearer distinction between expert opinion and evidence-based conclusions, and we have explicitly acknowledged areas where evidence remains limited or emerging.

Furthermore, we have clarified the role of the narrative literature review as supportive rather than systematic, and incorporated a more balanced discussion of limitations, uncertainties, and potential sources of bias, including those related to conflicts of interest.

We believe these revisions have improved the clarity, rigor, and overall balance of the manuscript, and we sincerely appreciate your valuable input.

Kind regards,

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

For author

This review article with the title of “A Global Delphi Consensus on Acne and the Microbiome: Integrating International Expertise for Innovative Prevention and Therapeutic Strategies” presents intriguing findings. I would like to offer some suggestions that may contribute to the enhancement of your article:

 

Abstract

• Kindly clarify the methodological approach, particularly how the Delphi process was conducted (e.g., number of rounds, criteria for consensus).
• Please consider adding more specific outcomes or key findings rather than general statements.
• It would be helpful to briefly indicate the clinical relevance or implications of the consensus.

 

Introduction

• Kindly ensure that species names are written in full at first mention and abbreviated appropriately in subsequent mentions.

 

Delphi Consensus Process and Methodological Approach

• Kindly provide more detail on the literature search strategy (e.g., keywords, inclusion/exclusion criteria).
• Please clarify how consensus thresholds (e.g., ≥75%) were determined and justified.
• It would be beneficial to include information on potential bias control, given the small expert panel size.
• Consider adding a flow diagram or structured summary of the Delphi process.

 

Pathogenesis: The Role of the Microbiome in Acne

• Kindly ensure that all scientific names (e.g., species names) are consistently written in italic throughout the manuscript.
• Kindly consider adding a schematic or summary table.

 

Relationship Between the Microbiome and the Skin Barrier

• Consider briefly discussing clinical implications of barrier restoration strategies.
• Kindly ensure that all scientific names (e.g., species names) are consistently written in italic throughout the manuscript.

 

The Microbiome and Acne Severity

• This section could benefit from additional supporting studies or quantitative data.

 

Positive Interventions and Cosmetic Adjuncts

• Kindly support statements with more clinical evidence, as current claims rely on limited data.

 

Lifestyle, Exposome, and Gut–Skin Axis

• This section could benefit from better structure, possibly dividing into subsections (diet, environment, skincare).

 

Results of the Global Delphi Process

• Kindly improve clarity by summarizing key findings in a more narrative synthesis, not only tables.
• Consider reducing redundancy between text and Table 1.

 

Practical Considerations and Future Perspectives

• Please consider adding a prioritization of future research directions.
• Some sections (e.g., phage therapy, vaccines) would benefit from more critical appraisal of limitations.

 

Author Response

We sincerely thank the reviewer for the thorough and constructive evaluation of our manuscript and for the valuable suggestions provided.

We have carefully revised the manuscript to address all the points raised:

• Introduction: Species names are now written in full at first mention and consistently abbreviated thereafter.
• Delphi methodology: The description of the literature search strategy has been expanded to include databases, key terms, and selection criteria. We have also clarified and justified the ≥75% consensus threshold based on established Delphi methodology standards. Additional details regarding bias control (including anonymized responses and iterative rounds) have been incorporated. A structured summary of the Delphi process, including a flow diagram (Figure 1), has been added to improve methodological transparency .
• Pathogenesis section: Scientific names have been standardized and italicized throughout. A schematic figure summarizing microbiome dynamics and acne development has been included (Figure 2).
• Skin barrier section: Clinical implications of barrier restoration strategies have been expanded to better connect mechanistic insights with clinical practice. Scientific nomenclature has been standardized.
• Microbiome and acne severity: Additional supporting references and quantitative insights have been incorporated to strengthen this section.
• Positive interventions: Statements have been revised to better reflect the current level of evidence, with additional references included and more cautious wording where appropriate.
• Lifestyle and exposome: This section has been restructured for clarity, with improved organization of key domains (diet, environment, skincare).
• Results section: A more narrative synthesis of the main findings has been added to complement Table 1, and redundancy between text and table has been reduced.
• Future perspectives: We have introduced a clearer prioritization of future research directions and expanded the critical appraisal of emerging strategies such as phage therapy and vaccines, including their current limitations.

We believe these revisions have significantly improved the clarity, scientific rigor, and overall structure of the manuscript, and we appreciate the reviewer’s insights, which were instrumental in strengthening the work.

Please see the attachment

Author Response File: Author Response.docx

Reviewer 3 Report

Comments and Suggestions for Authors

This manuscript addresses a timely and clinically relevant topic and presents an international Delphi-based expert consensus on the role of the microbiome in acne pathogenesis and treatment. The paper is generally well written, clinically focused, and offers a useful framework linking dysbiosis, barrier dysfunction, exposome-related factors, inflammation, and acne outcomes. That said, I do not think the manuscript is ready for acceptance in its current form and would recommend major revision.

My main concern is the limited methodological detail provided for the Delphi process. At present, the description is too brief to allow readers to judge the rigor of the consensus procedure. In addition, several statements appear to be phrased more strongly than the available evidence supports, and the manuscript does not always clearly distinguish between evidence-based conclusions and expert opinion.

Specific comments:

In the pathogenesis section, “Such as C. acnes type IA1” should be corrected to “such as C. acnes type IA1.”

The authors should consider adding an evidence map or a supplementary table showing the key references and level of evidence supporting each consensus statement. As it stands, Table 1 reports only the level of agreement, without indicating the strength of the underlying evidence. For a clinically oriented readership, this would be helpful.

The abstract would benefit from some language editing for clarity. For example, the phrase “the exposome influence and immune response interactions have on this complex microbial system” is awkward and should be revised.

Since the manuscript is structured around a Delphi process, it would be useful to include a simple flow diagram or supplementary table summarizing how the statements were developed, how many rounds were conducted, and what the final outcomes were. This would improve both readability and methodological transparency.

The manuscript would also benefit from a clearer discussion of the biological context surrounding skin inflammation and wound-associated immune responses. At present, the Discussion is rather brief in this regard.  For example：Acne may related immune part in biology：The infundibulum, where hair follicles engage with external environments, is noted. Resident Langerhans cells, found in the upper section of the hair follicle, are crucial for overseeing the follicular canal and detecting potential pathogen invasions. Furthermore, as the infundibulum hosts various microbes, the local immune cell population may be influenced by the microbiome of the hair follicles (Moresi JM, J Cutan Pathol. 1997; Jaworsky C, Br J Dermatol. 1992)（Anita Gola，2026）. It is reported that upper HFSCs and the filling of sebaceous glands (SGs) (Han, J., iScience 2023) play significant roles. HFSCs and SG cells within these glands can further develop into sebaceous cells, contributing positively to wound healing (Han, J., iScience 2023).may help place the present work into a broader and more current biological framework. Expanding this part of the Discussion would make the manuscript more informative and better connected to the recent literature.

 

Overall, this is a potentially useful manuscript on an important topic, but substantial revision is needed before it can be considered for publication. In particular, the paper would be strengthened by a fuller description of the Delphi methodology, a clearer distinction between evidence and expert opinion, more restrained wording where the evidence base is still limited, and a more explicit discussion of the study’s limitations and potential conflict-related bias.

Author Response

We sincerely thank the reviewer for the thoughtful and constructive comments, and we appreciate the recognition of the clinical relevance of our work.

We fully agree with the points raised and have carefully revised the manuscript accordingly. Specifically, we have expanded the description of the Delphi methodology to improve transparency and allow better assessment of the rigor of the consensus process. We have also clarified throughout the text the distinction between evidence-based conclusions and expert opinion, while preserving the integrity of the original consensus statements.

In addition, we have addressed all specific comments, including correction of minor language issues, revision of the abstract for clarity, and refinement of the overall wording where appropriate. To strengthen the manuscript, we have added a supplementary evidence table detailing the level of evidence supporting each consensus statement, as well as a flow diagram summarizing the Delphi process.

Finally, the Discussion section has been expanded to better contextualize the biological framework of acne, incorporating recent insights into follicular immunology, the role of Langerhans cells, and hair follicle stem cell dynamics in inflammation and tissue repair.

We believe these revisions have significantly improved the clarity, rigor, and overall quality of the manuscript, and we hope it is now suitable for publication.

Please see the attachment

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear authors,

Thank you for revising the manuscript.

I suggest to enlarge Fig.1, as it is difficult to read the letters by now.

 

Reviewer 3 Report

Comments and Suggestions for Authors

The English is fine and does not require further improvement, and the paper is suitable for publication.