Oral Microbiota in Patients with Alzheimer’s Disease: A Systematic Review

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

 

Review of Manuscript: "Oral Microbiota in Patients with Alzheimer’s Disease: A Systematic Review"

 

The manuscript provides a valuable systematic review exploring the associations between oral microbiota and Alzheimer’s Disease (AD). The topic is highly relevant, given the increasing interest in the potential links between oral health and neurodegenerative diseases. The manuscript is generally well-structured and clear. However, there are several areas where improvements are necessary to enhance the clarity and impact of the work.

 

Please see below.

 

Abstract:

• Acronyms: The term "AD" is used in the abstract without being defined first. Please ensure that "Alzheimer’s Disease (AD)" is spelled out initially.
• Line 21: There is a typo in "add the date." It should be corrected.
• Conclusions: The abstract would benefit from a more explicit statement of the conclusions. Currently, it focuses more on the methodology and results without a clear take-home message. Consider summarizing the implications of your findings in one or two sentences.

 

Introduction:

• Aim of the Study: The aim of the study is mentioned but not highlighted as a distinct paragraph. It would improve clarity to state the aim explicitly in a separate, concise paragraph to ensure that readers can quickly understand the study's purpose.

 

Material and Methods:

• This section is well-constructed, providing a clear and detailed description of the methods used in the systematic review. No major changes are needed.

 

Results:

• The results section is appropriately detailed and structured. The presentation of data is clear and logical. No major issues were identified in this section.

 

Discussion:

• The discussion is thorough and well-argued. It effectively ties the findings to the existing literature, highlighting both strengths and limitations. No additional changes are necessary.

 

Conclusions:

• The conclusions section succinctly summarizes the key findings of the review. It effectively communicates the need for further research in this area. The section is well-written and does not require any changes.

 

Additional Suggestions:

• Consistency in Terminology: Ensure that the terminology used throughout the manuscript is consistent. For example, "oral microbiota" and "oral microbiome" are sometimes used interchangeably. It might be helpful to choose one term and stick with it unless a distinction is being made.
• Figures and Tables: Ensure that all figures and tables are clearly labeled and referenced in the text. Double-check for any inconsistencies between the text and the labels in these elements.

 

Overall, the manuscript is a solid contribution to the field, addressing a significant and timely topic. With the incorporation of the suggested revisions, it will be suitable for publication.

 

Best regards!

Author Response

We appreciate the extensive reading and helpful comments of the reviewers. We discuss their comments below. The comments of the reviewers are written in italics, our response is written in bold. Page numbers refer to the revised version of the manuscript.

Reviewer 1

The manuscript provides a valuable systematic review exploring the associations between oral microbiota and Alzheimer’s Disease (AD). The topic is highly relevant, given the increasing interest in the potential links between oral health and neurodegenerative diseases. The manuscript is generally well-structured and clear. However, there are several areas where improvements are necessary to enhance the clarity and impact of the work.

Please see below

Abstract:

• Acronyms: The term "AD" is used in the abstract without being defined first. Please ensure that "Alzheimer’s Disease (AD)" is spelled out initially.

Thank you for your comment; we have adjusted them on page 1, sentences 19-22.

'Oral microorganisms have been found in the cerebral milieu suggesting involvement of oral microbiota in the onset and course of Alzheimer’s Disease (AD) through mechanisms such as amyloid-beta accumulation, tau phosphorylation and neuroinflammation.'

• Line 21: There is a typo in "add the date." It should be corrected.

Thank you for pointing out the error, we have changed it accordingly. Page 1, sentences 24-25.

'The database search in Pubmed and Embase resulted in 623 hits. After removing duplicates, 437 papers remained.'

Conclusions: The abstract would benefit from a more explicit statement of the conclusions. Currently, it focuses more on the methodology and results without a clear take-home message. Consider summarizing the implications of your findings in one or two sentences.

Your observations are highly valued. We have adjusted them on page 1, sentences 31-37.

'There is no conclusive evidence as to if and which oral microbiota are associated with AD, since many conflicting results were reported. Although the overall quality of the studies was acceptable, the studies differed in study design and protocol. Further research is needed to clarify this.'

Introduction:

• Aim of the Study: The aim of the study is mentioned but not highlighted as a distinct paragraph. It would improve clarity to state the aim explicitly in a separate, concise paragraph to ensure that readers can quickly understand the study's purpose.

Thank you again for your constructive criticism. We have adjusted them on page 2, sentences 76-77.

Material and Methods:

• This section is well-constructed, providing a clear and detailed description of the methods used in the systematic review. No major changes are needed.

Thank you very much for your insightful feedback.

Results:

• The results section is appropriately detailed and structured. The presentation of data is clear and logical. No major issues were identified in this section.

Thank you very much for your feedback.

Discussion:

• The discussion is thorough and well-argued. It effectively ties the findings to the existing literature, highlighting both strengths and limitations. No additional changes are necessary.

I am grateful for your thorough evaluation.

Conclusions:

• The conclusions section succinctly summarizes the key findings of the review. It effectively communicates the need for further research in this area. The section is well-written and does not require any changes.

Thank you for your encouraging words.

Additional Suggestions:

• Consistency in Terminology: Ensure that the terminology used throughout the manuscript is consistent. For example, "oral microbiota" and "oral microbiome" are sometimes used interchangeably. It might be helpful to choose one term and stick with it unless a distinction is being made.
• Figures and Tables: Ensure that all figures and tables are clearly labeled and referenced in the text. Double-check for any inconsistencies between the text and the labels in these elements.

Thank you for your valuable input, which we have incorporated throughout the document. We have adjusted them on page 5, sentences 126-128 and page 8, sentence 178.

‘Each group had an adapted ‘ideal score’ due to some subjects that could not be scored (supplementary table 1: items 6 until 12 for non-comparative studies and items 6 and 7 for comparative studies).’

‘The quality assessment, conducted using the MINORS criteria (Supplementary table 1), categorized the included articles into three groups: good quality, medium quality or poor quality, indicated by color (green, orange, and red). ’

Overall, the manuscript is a solid contribution to the field, addressing a significant and timely topic. With the incorporation of the suggested revisions, it will be suitable for publication.

Thank you for taking the time to provide your feedback.

 

Best regards!

Reviewer 2 Report

Comments and Suggestions for Authors

In the reviewed paper, the authors showed ambiguous results regarding the association of oral microbiota and Alzheimer’s disease. The studies were properly conducted, according to the Preferred Reporting Items for Systematic Reviews (PRISMA) guideline, Methodological Index for Non-Randomized Studies (MINORS) criteria and were registered in PROSPERO. The studies ultimately included 13 publications, providing for each of them the characteristics of the patients, sequencing or RT-PCR method, main findings and limitations.

Corrections:

1. I propose to add in Table 3 what the level of relative abundance was, e.g. 3-fold increase or 5-fold decrease from the control.

2. Data on specific species should be presented in the form of a color graph, together with the level of relative abundance. This would help the reader to quickly see which bacteria are increasing or decreasing and by how much.

Comments on the Quality of English Language

OK

Author Response

We appreciate the extensive reading and helpful comments of the reviewers. We discuss their comments below. The comments of the reviewers are written in italics, our response is written in bold. Page numbers refer to the revised version of the manuscript.

In the reviewed paper, the authors showed ambiguous results regarding the association of oral microbiota and Alzheimer’s disease. The studies were properly conducted, according to the Preferred Reporting Items for Systematic Reviews (PRISMA) guideline, Methodological Index for Non-Randomized Studies (MINORS) criteria and were registered in PROSPERO. The studies ultimately included 13 publications, providing for each of them the characteristics of the patients, sequencing or RT-PCR method, main findings and limitations.

Corrections:

1. I propose to add in Table 3 what the level of relative abundance was, e.g. 3-fold increase or 5-fold decrease from the control.

Thank you for your thorough evaluation. Unfortunately, it is not possible because the data do not allow it due to different methodologies and the lack of a concrete factor regarding the ratio between the control and AD groups.

2. Data on specific species should be presented in the form of a color graph, together with the level of relative abundance. This would help the reader to quickly see which bacteria are increasing or decreasing and by how much.

Thank you for taking the time to provide your feedback. Unfortunately, it is not possible in this case either, as the data do not allow it due to differences in methodology and the lack of a concrete factor between the control and AD groups in the various studies.

Reviewer 3 Report

Comments and Suggestions for Authors

Ref: applsci-3192642-peer-review-v1

This is an interesting systematic review concerning the relation between oral microbiota and Alzheimer’s disease.

The study is well-designed and methodology is more than adequate. Despite the hypothesis of involvement of oral bacteria in the pathogenesis of sporadic Alzheimer’s disease, the main finding of the present review is that, so far, published studies show significant variation concerning methodology, resulting in conflicting results. In particular, differences in methodology include different specimens studied (saliva, dental plaque, mucosal swabs), different microbiological approach, incomplete records on smoking or oral hygiene habits. According to the results, no definite conclusion can be reached as to if and which bacteria are associated with Alzheimer pathology, necessitating further studies with strict methodology. Providing such information, I believe the review merits publication. I have no specific comments.

Author Response

We appreciate the extensive reading and helpful comments of the reviewers. We discuss their comments below. The comments of the reviewers are written in italics, our response is written in bold. Page numbers refer to the revised version of the manuscript.

This is an interesting systematic review concerning the relation between oral microbiota and Alzheimer’s disease.

The study is well-designed and methodology is more than adequate. Despite the hypothesis of involvement of oral bacteria in the pathogenesis of sporadic Alzheimer’s disease, the main finding of the present review is that, so far, published studies show significant variation concerning methodology, resulting in conflicting results. In particular, differences in methodology include different specimens studied (saliva, dental plaque, mucosal swabs), different microbiological approach, incomplete records on smoking or oral hygiene habits. According to the results, no definite conclusion can be reached as to if and which bacteria are associated with Alzheimer pathology, necessitating further studies with strict methodology. Providing such information, I believe the review merits publication. I have no specific comments.

Thank you for your kind words and for taking the time to review the manuscript.

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors significantly corrected the manuscript according to the reviewer's suggestions. Recently, I recommend the article for publication.

Comments on the Quality of English Language

OK