Mucosal Immunity and Trained Innate Immunity of the Gut

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Authors present a comprehensive and up-to date review on the immunity of the human gut. As an entomologist I cannot adequately assess the scientific value of the overview for human medicine, but I liked the manuscript. I can see a lot of parallels between mammalian/human and insect immunity. The manuscript needs some editorial improvement.

- line 157 and others: give references in the text correctly (no surnames, abbreviations, etc.)

- line 200 and others: do you mean secretory IgM, IgA etc.line 215: ? then use sIgM as in other cases

- line 215: give all subheadings in lowercase letters

- line 238: close the bracket

- line 290: are presented

- line 301 and others: et al.,

- line 306 and others: explain acronyms when first used in the text or give a list of abbreviations

- line 317 and others: why here in uppercase letters?

- line 324 and others: give all species names in italics

- 6.3 not in bold

- References: give titles of papers either in lowercase or in uppercase letters, but not mixed

 

Comments on the Quality of English Language

English is mainly fine.

Author Response

Comments and Suggestions for Authors

Authors present a comprehensive and up-to date review on the immunity of the human gut. As an entomologist I cannot adequately assess the scientific value of the overview for human medicine, but I liked the manuscript. I can see a lot of parallels between mammalian/human and insect immunity. The manuscript needs some editorial improvement.

• Authors` reply: Thank you very much for your positive feedback and thoughtful comments on our manuscript. We appreciate your perspective as an entomologist and are glad to hear that you found such parallels. Your recognition of the comprehensive and up-to-date nature of our overview is greatly appreciated.
• We acknowledge your note on the need for improvement and will ensure that the manuscript undergoes further refinement to enhance its clarity and readability. Thank you again for your valuable input.

- line 157 and others: give references in the text correctly (no surnames, abbreviations, etc.)

• Authors` reply: Thank you, we corrected the issue.

- line 200 and others: do you mean secretory IgM, IgA etc.line 215: ? then use sIgM as in other cases

Authors` reply: Yes, we meant secretory immunoglobulins, therefore, we changed to the proper sIgA and sIgM.

- line 215: give all subheadings in lowercase letters

Authors` reply: We corrected this and the other subheadings in the manuscript.

- line 238: close the bracket

Authors` reply: Thank you for the meticulous precision.

- line 290: are presented

- Corrected.

- line 301 and others: et al.,

- Corrected.

- line 306 and others: explain acronyms when first used in the text or give a list of abbreviations

- We corrected this issues and the other terms in the text via introducing the abbreviations at their first appearance.

- line 317 and others: why here in uppercase letters?

- The misspelling is corrected.

- line 324 and others: give all species names in italics

- We corrected the issue.

- 6.3 not in bold

- the issue is corrected.

 

- References: give titles of papers either in lowercase or in uppercase letters, but not mixed

• The references will be corrected further as per yours and journal requirements. All of the above-mentioned issues are corrected regarding your recommendations.

 

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript explores the relationship between mucosal immunity and trained innate immunity in the gut, focusing on their roles in gastrointestinal diseases and potential therapeutic implications. Firstly, it compares innate and trained immunity. Then, it discusses how mucosal immune responses in the gut are influenced by trained immunity. Specifically, it delves into the mechanisms underlying trained immunity. Furthermore, the manuscript discusses therapeutic implications, including the use of biologics and targeted therapies to modulate immune responses in IBD, as well as emerging trends such as the manipulation of gut microbiota and the potential role of pre- and postbiotics. It concludes by emphasizing the importance of understanding mucosal and trained innate immunity for developing novel therapeutic strategies to restore intestinal homeostasis in gastrointestinal disorders. However, several questions still remain:

The authors could discuss the limitations of current research models and potential strategies to overcome them.

The Search strategy section does not provide further details on other inclusion criteria, such as publication date range or study design.

It would enhance comprehension by including diagrams or figures to illustrate the mechanisms and interactions described in the manuscript.

The authors could address the role of other factors in modulating mucosal immunity, including diet, sex, aging, race, environmental exposure.

Minor:

Extra space between 1. and Introduction

Missing space between 2. and Search strategy

6.3 Influence of dysregulated immunity on gut disorders should not bold.

Author Response

Comments and Suggestions for Authors

The manuscript explores the relationship between mucosal immunity and trained innate immunity in the gut, focusing on their roles in gastrointestinal diseases and potential therapeutic implications. Firstly, it compares innate and trained immunity. Then, it discusses how mucosal immune responses in the gut are influenced by trained immunity. Specifically, it delves into the mechanisms underlying trained immunity. Furthermore, the manuscript discusses therapeutic implications, including the use of biologics and targeted therapies to modulate immune responses in IBD, as well as emerging trends such as the manipulation of gut microbiota and the potential role of pre- and postbiotics. It concludes by emphasizing the importance of understanding mucosal and trained innate immunity for developing novel therapeutic strategies to restore intestinal homeostasis in gastrointestinal disorders. However, several questions still remain:

• Thank you for your thoughtful and detailed feedback on our manuscript. We appreciate your comprehensive summary of our work and your recognition of its relevance to the field of gastrointestinal diseases and immunology. We acknowledge that some issues remain, and we are committed to addressing these in our revised manuscript. We are grateful for your constructive comments and believe they will significantly enhance the quality and clarity of our manuscript. Thank you for your valuable input and for helping us improve our work.

The authors could discuss the limitations of current research models and potential strategies to overcome them.

• Thank you for the valuable recommendations, we added a passage to address the limitations of the mentioned research models. Additionally, the paragraph from lines 480 to 486 is devoted to commenting on the limitations of the current models, and also that NGS and fecal transplant models could help to overcome them.

The Search strategy section does not provide further details on other inclusion criteria, such as publication date range or study design.

• Thank you for noticing that. We have added the missing details.

It would enhance comprehension by including diagrams or figures to illustrate the mechanisms and interactions described in the manuscript.

• The referee is right to point out that a figure will make the topic more comprehensive, although we have a figure describing the concept of trained innate immunity.

The authors could address the role of other factors in modulating mucosal immunity, including diet, sex, aging, race, environmental exposure.

• We have added a passage on this particular topic, thank you for pointing this to us.

 

Minor:

Extra space between 1. and Introduction

Missing space between 2. and Search strategy

6.3 Influence of dysregulated immunity on gut disorders should not bold.

• Authors` reply. The extra space and missing space seems to be related to the formatting of the template and we hope to be resolved with the help of the editorial team. The 6.3. subheading was corrected accordingly. Thank you for your meticulous precision.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript is well planned, well designed and well written. I have following suggestions to improve it. 

 

Please write few more sentences in your abstract. 

Please add some tables summaizing the data of cited research results and methods or models used. 

Please add illustrated figures for each of the process or topics described. That will make the topics more easy for the readers. 

 

Comments on the Quality of English Language

Please revise the English and try to improve. 

Author Response

Comments and Suggestions for Authors

The manuscript is well planned, well designed and well written. I have following suggestions to improve it. 

• Thank you for your positive feedback on our manuscript. We appreciate your opinion on our paper. We welcome your suggestions for improvement and are eager to address them to enhance the quality of our work. Your constructive input is invaluable to us, and we are committed to making the necessary revisions based on your recommendations.
• Thank you once again for your time and effort in reviewing our manuscript.

Please write few more sentences in your abstract. 

• Thank you for the suggestion. We revise the abstract to make it more clear, detailed and comprehensive.

Please add some tables summaizing the data of cited research results and methods or models used. 

• Thank you for the recommendation. We prepared a table.

Please add illustrated figures for each of the process or topics described. That will make the topics more easy for the readers. 

• The referee is right to point out that a figure will make the topic more comprehensive. Although we had one figure, we added another one.

 

Comments on the Quality of English Language

Please revise the English and try to improve. 

• We appreciate your suggestion to revise and improve the English. We have thoroughly reviewed the manuscript and made necessary revisions to enhance the clarity and readability of the text.