The Multifaceted Effects of Gut Microbiota on the Immune System of the Intestinal Mucosa
Round 1
Reviewer 1 Report
The review article provided by Hirano and Nakase represents a compact review about several aspects of the effects of the gut microbiota on the immune system and intestinal mucosa. Overall the manuscript is written well, however, it would benefit from a stronger connection between the individual parts, putting them in a larger context. Furthermore, some statements seem to be overstating the points the authors would like to make.
For example, why is the metabolism and uptake of PUFAs described, including the production of 10-hydroxy-cis-12-octadeccenoid acid? By adding a few words on the importance of this metabolite, the information given could be placed much better into context by readers from outside the field. In this paragraph the sentence “(PUFAs), such as linoleic acid and α-linolenic acid, have physiologically important roles and are called essential fatty acids, even though they are not synthesized in the human body” would need to be changed to ……., because they are not synthesized by the human body” (lines 76-77).
Also for table 1 it might be interesting to distinguish between internal membranes and the plasma membrane as location for the PRRs listed. A sentence on why just the one protein of the many signalling molecules involved in PRR-mediated signalling is listed table 1 might also help the reader to put this into a larger context.
The authors might also think about modifying some formulations like in line 96-97, “…promoting bacterial the clearance of pathogenic bacteria [23-24]”. Is clearance the correct description for describing a gut environment, or is it merely a reduction of pathogens.
For the chapter 3.2 the last sentence (line 249 and 250) “Thus, studies on the involvement of Tregs in CAC are required in the future [87].” ends with a reference from 2010. I wonder, whether the paragraph actually represents the state of the art from 2010. This might be corrected (or updated).
In the COVID-19 chapter a few points should be modified. The statement in lines 253-4 “… the current World Health Organization release, more than 230 million people have been infected and 4.7 million people have died to date ... ” needs a citation with date, since the numbers are changing on a daily basis.
ACE-2 stands for Angiotensin-converting enzyme-2; NOT for Acetlycholine-2 receptors (AChR).
Although reports in the literature describe anorexia as a symptom in COVID-19 patients in the context of loss of appetite, it might be considered to change anorexia (line 261) to loss of appetite in order to avoid confusion with the clinical indications of anorexia nervosa etc.
For the conclusion, the three issues yet to be elucidated are given in very general terms. For me it is not clear to which of the possible and manifold diseases described in the manuscript the authors refer to in issue (2) (line 298), especially if there is any disease where clear patterns of dysbiosis are already documented, which for example might help in diagnostic or even therapeutic approaches.
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Hirano et al nicely describe the multifaceted effects of the gut microbiota on several diseases from the perspective of mucosal immunological responses particularly in COVID-19. The review is well written and scientifically sound.
However here are few minor comment that the authors can improve the manuscript.
- The paper is well referenced, however, line 52, 62 and 116 need to be reference.
- I find the figure 1 does not give a clear picture of the role of gut microbiota in dietary metabolism and defense. please revise
- Abbreviation such as IBD and AIEC should be written in full for the first instance
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
All suggestions for modification of the manuscript by Hirano and Nakase have been implemented. I have no further suggestions for modification.
