The Connection Between the Oral Microbiota and the Kynurenine Pathway: Insights into Oral and Certain Systemic Disorders

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The man presents an in-depth review of the relationship between the oral microbiome and the kynurenine pathway, exploring its relevance in various oral disorders such as periodontal disease, dental caries, oral candidiasis, and oral cancer. The topic is timely and has the potential to contribute significantly to the understanding of how microbial imbalances and metabolic pathways are intertwined in oral health and systemic diseases. However, I was wondering if the fourth part ”Impact of the oral microbiome on systemic disorders” has any relationship with the topic kynurenine pathway. Pls explain the necessity of the fourth part. Meanwhile, English edits are needed throughout the manuscript.

Comments on the Quality of English Language

The English could be improved to more clearly express the research.

Author Response

Comments 1: The man presents an in-depth review of the relationship between the oral microbiome and the kynurenine pathway, exploring its relevance in various oral disorders such as periodontal disease, dental caries, oral candidiasis, and oral cancer. The topic is timely and has the potential to contribute significantly to the understanding of how microbial imbalances and metabolic pathways are intertwined in oral health and systemic diseases. However, I was wondering if the fourth part ”Impact of the oral microbiome on systemic disorders” has any relationship with the topic kynurenine pathway. Pls explain the necessity of the fourth part.

Response 1: Thank you for the reviewer’s comments, which have helped improve the quality of the manuscript. Chapter 4 introduces several systemic diseases in which both dysbiosis and the KP may play a role in the pathomechanism. We have expanded the section on the connection between Chapter 4 and the KP within the text.

Comments 2: Meanwhile, English edits are needed throughout the manuscript.

Response 2: Additionally, we have revised the English throughout the manuscript with the assistance of a native English speaker to ensure clarity and accuracy.

 

Reviewer 2 Report

Comments and Suggestions for Authors

The reviewer appreciates the effort of the authors to initiate a narrative review of an interesting topic. It is an important area that needs to be explored and discussed more. However, after careful review, the reviewer has the following comments and suggestions on the manuscript:

The types of review (narrative review) need to be mentioned in the abstract.

The author should state the specific objectives of this narrative review which should align with the title and content of the manuscript.

The pathway illustrated in Figure 2 is different than the cited reference (32, 33). The author can generate an original illustration using appropriate apps like BioRender, Adobe, etc and present it in the manuscript without referring particular article in the figure legend. Alternatively, if the author wants to re-use the illustration of any published article, please obtain a copyright from the journal and mention the copyright statement in the figure legend.

The subsections of sections 3 and 4 need to be improved by adding an appropriate illustration that supports the text of the corresponding sub-sections. The author can generate an original hypothetical illustration using appropriate apps like BioRender, Adobe, etc, or re-use the illustrations of published articles with proper copyright

The conclusion needs to be precise highlighting the particular outcome of the review.  

 

The similarity index is very high (34%). Please conduct a major revision of the text using proper paraphrasing.  

Author Response

Comments 1: 

The reviewer appreciates the effort of the authors to initiate a narrative review of an interesting topic. It is an important area that needs to be explored and discussed more. However, after careful review, the reviewer has the following comments and suggestions on the manuscript:

The types of review (narrative review) need to be mentioned in the abstract.

Response 1: 

Thank you for the comment; this is included in the abstract.

 

Comments 2: 

The author should state the specific objectives of this narrative review which should align with the title and content of the manuscript.

Response 2:

Thank you for the comment; we have modified the abstract and the title as well.

Comments 3:

The pathway illustrated in Figure 2 is different than the cited reference (32, 33). The author can generate an original illustration using appropriate apps like BioRender, Adobe, etc and present it in the manuscript without referring particular article in the figure legend. Alternatively, if the author wants to re-use the illustration of any published article, please obtain a copyright from the journal and mention the copyright statement in the figure legend.

Response 3:

Of course, we created our own figure, and the references included in the figure caption are for further clarification, not the sources of the image, as we did not indicate them as such.

Comments 4:

The subsections of sections 3 and 4 need to be improved by adding an appropriate illustration that supports the text of the corresponding sub-sections. The author can generate an original hypothetical illustration using appropriate apps like BioRender, Adobe, etc, or re-use the illustrations of published articles with proper copyright.

Response 4:

Thank you for the comment; we have modified the figures along with the feedback from the other reviewers. In addition, we created a new illustration (Fig. 5) intended to showcase the entire process.

Comments 5:

The conclusion needs to be precise highlighting the particular outcome of the review. 

Response 5:

Thank you; we have supplemented the conclusion.

Comments 6:

The similarity index is very high (34%). Please conduct a major revision of the text using proper paraphrasing.

Response 6:

Thank you for the comment; unfortunately, we have not yet received feedback from the Publisher regarding the similarity. We reference numerous previous research results of our own, but in every case, we try to rephrase the results we have previously written.

Reviewer 3 Report

Comments and Suggestions for Authors

This study reviews the role of the oral microbiome in health, noting how microbial imbalances contribute to dental and periodontal diseases. It highlights how the kynurenine pathway, influenced by microbial tryptophan metabolism, connects oral microbiome composition to immune regulation and inflammation, impacting overall health. However, I think this manuscript needs to introduce more about the role of interaction between kynurenine pathway and oral microbiome in the different diseases.

Major comments:

1. Section 4.3, what's the role of kynurenine pathway in neurological disorders? How does the oral microbiome interact with KP and then affect the patients of neurological disorders?

2. The figure 4 didn't show the role of kynurenine pathway in these diseases. Could authors revise it to show more interaction/connection between microbiomes and KP in these diseases?

3. Line 223-229, is this paragraph a summary of previous research? If so, please add reference. If not, it's hard to prove the connection between caries and KP.

4. I suggest changing figure 3 to a table. And could author integrate the interaction between oral microbiome and KP into figure 2? It would be best to show which steps of kynurenine system were affected by oral microbiome.

5. Figure 2, I suggest label each arrow with a, b, c...., then add the label into the text. This could make it be easier to follow.

Minor comments:

1. Make sure all microbiome names are italic.

2. Line 215-216, please add reference.

3. Make sure all hyphens are correct.

 hyphen

Author Response

Comments 1: 

This study reviews the role of the oral microbiome in health, noting how microbial imbalances contribute to dental and periodontal diseases. It highlights how the kynurenine pathway, influenced by microbial tryptophan metabolism, connects oral microbiome composition to immune regulation and inflammation, impacting overall health.

However, I think this manuscript needs to introduce more about the role of interaction between kynurenine pathway and oral microbiome in the different diseases.

Response 1:

Thank you for the reviewer’s comments, which have helped to improve the quality of the manuscript. We have expanded the section addressing the connection between KP and the oral microbiome.

 

Comments 2: 

Section 4.3, what's the role of kynurenine pathway in neurological disorders? How does the oral microbiome interact with KP and then affect the patients of neurological disorders?

Response 2: 

Thank you for your feedback; we have revised the chapter accordingly.

 

Comments 3:

The figure 4 didn't show the role of kynurenine pathway in these diseases. Could authors revise it to show more interaction/connection between microbiomes and KP in these diseases?

Response 3: 

Thank you for the feedback; we have modified the figure, but unfortunately, it is not possible to represent this complex array of kynurenine metabolites in a single figure.

 

Comments 4: 

Line 223-229, is this paragraph a summary of previous research? If so, please add reference. If not, it's hard to prove the connection between caries and KP.

Response 4: 

Thank you very much for pointing out this error. We have indeed relied on research findings, and we have added the missing reference.

 

Comments 5:

I suggest changing figure 3 to a table. And could author integrate the interaction between oral microbiome and KP into figure 2? It would be best to show which steps of kynurenine system were affected by oral microbiome.

Response 5:

Thank you for the comment. We replaced Figure 3 with a table, and we modified Figure 2.

 

Comments 6: 

Figure 2, I suggest label each arrow with a, b, c...., then add the label into the text. This could make it be easier to follow.

Response 6: 

Thank you for the comment; we have added the labels and indicated them in the text as well.

 

Comments 7:

Make sure all microbiome names are italic.

Response 7:

Thank you for the notice; we have corrected the incorrect fonts.

 

Comments 8: 

Line 215-216, please add reference.

Response 8:

We have indicated the reference in the text.

 

Comments 9:

Make sure all hyphens are correct.

Response 9:

Thank you for the notice; a native English speaker has reviewed it.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

I have no further comments on the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for the point-by-point reply to the reviewer's comment. The revision is satisfactory. The only remaining concern is the high similarity index. Please reduce the similarity index to an acceptable level. good luck

Reviewer 3 Report

Comments and Suggestions for Authors

All the comments have been well addressed. I have no more questions.