Gut Metabolism of Sugars: Formation of Glycotoxins and Their Intestinal Absorption

Round 1

Reviewer 1 Report

In this manuscript, the authors will carry out a review bringing together current knowledge about the formation of glycotoxins from dietary sugars and gut metabolism of sugars. In this paper, the authors showed that the microbial fraction also has incredible importance regarding the molecules absorbed, and the presence of certain strains is often mandatory for the development of physiological and pathological processes.

This review is original and relevant. The work is well written and does not need significant improvement. 

Author Response

RESPONSE TO REVIEWERS

We deeply thank the editors and reviewers for their assessment of the manuscript. We have acted upon the recommendations of the reviewers in order to improve the manuscript quality. Below we added our point-by-point responses to each comment. In addition, we highlighted revisions in yellow in the updated manuscript.

 

 

REVIEWER 1:

 

In this manuscript, the authors will carry out a review bringing together current knowledge about the formation of glycotoxins from dietary sugars and gut metabolism of sugars. In this paper, the authors showed that the microbial fraction also has incredible importance regarding the molecules absorbed, and the presence of certain strains is often mandatory for the development of physiological and pathological processes. This review is original and relevant. The work is well-written and does not need significant improvement.

 

We deeply thank the reviewer for the comments made by the reviewer and the careful reading of the manuscript.

 

Reviewer 2 Report

In this article, Alfredo et al review the modes of glycotoxin formation from sugars, their digestion, and their absorption mechanism. The article is well-written and sheds light on the possible mechanisms of alteration to gut homeostasis in metabolic conditions like diabetes.

The authors need to address the following concerns to make the article comprehensive:

1.       Although the article touches upon several important aspects of glycotoxin formation and absorption, the authors need to discuss a few other important topics, including – a) their effects on cellular function, b) reports of in vitro and in vivo experiments on AGEs and other glycotoxins, c) expand on the gut microbiota section as plays a tremendous role in glycotoxin metabolism and intestinal homeostasis. Addition of these topics would also address the issue of novelty as there have been a few reviews on the same topic in the last few years.

 

2.       The authors need to add an additional section discussing the implications of the glycotoxin literature on the diagnosis and/or treatment of different disorders.

Author Response

RESPONSE TO REVIEWERS

We deeply thank the editors and reviewers for their assessment of the manuscript. We have acted upon the recommendations of the reviewers in order to improve the manuscript quality. Below we added our point-by-point responses to each comment. In addition, we highlighted revisions in yellow in the updated manuscript.

 

REVIEWER 2:

 

In this article, Alfredo et al review the modes of glycotoxin formation from sugars, their digestion, and their absorption mechanism. The article is well-written and sheds light on the possible mechanisms of alteration to gut homeostasis in metabolic conditions like diabetes.

 

We deeply thank the reviewer for the comments made by the reviewer and the careful reading of the manuscript.

 

 

The authors need to address the following concerns to make the article comprehensive:

1. Although the article touches upon several important aspects of glycotoxin formation and absorption, the authors need to discuss a few other important topics, including – a) their effects on cellular function, b) reports of in vitro and in vivo experiments on AGEs and other glycotoxins, c) expand on the gut microbiota section as plays a tremendous role in glycotoxin metabolism and intestinal homeostasis. Addition of these topics would also address the issue of novelty as there have been a few reviews on the same topic in the last few years.

We agree with the reviewer that those specific topics would increase the level of the manuscript. In fact, they were already described in previous publications from our group (doi: 10.1002/med.21410; doi:10.3390/diabetology1010004). This manuscript in particular is included in a series of invited review articles focusing on different aspects of dietary sugars and AGEs formation (https://www.mdpi.com/journal/diabetology/special_issues/sugar_obesity_diabetes). One of the articles will focus precisely the relation between gut microbiota and dietary sugars, while others will focus for instance nutritional aspects, their role in immune cell metabolism, etc. In fact, that is the reason why the review only has ~3000 words, it is the word count limit for the reviews.

 

 

2. The authors need to add an additional section discussing the implications of the glycotoxin literature on the diagnosis and/or treatment of different disorders.

 

This information was included in the introduction. A new section was not created because of the word count limit in this series of short reviews. Also, the topic is well covered by other reviews, some of them cited in this manuscript.

Reviewer 3 Report

Summary

In this review article, the authors Monterio-Alfredo et al., is providing an outline about the details regarding overall glycotoxin formation and their digestion in the gastrointestinal system.

The authors also focused on the intestinal absorption of the glycotoxins. The overall review emphasizes on the harmful effects caused by the advanced glycation end products (AGEs) and the major target molecules that might be involved in the AGE metabolism which may affect the homeostasis and prompt the onset of several metabolic and immunological diseases. The authors suggests that, identifying the molecules to prevent the absorption of AGEs would reduce the harmful effects of AGEs.

Comments

1.The overall focus of the review is clear.

2.In the introduction, the authors mentioned that the AGEs have been associated with the insulin resistance in the obese models. It would be more informative if the authors could also specify the type of animal model (rat or mouse model etc.) that was used in the cited study.

3.The authors stated that, AGEs may be cleared by Amadoriases. Could the authors add few sentences explaining the amadoriases ?

4.Are there any approaches for the quantification of AGEs? If there are any, can the authors include them in this review in a subsection.

5. Can the authors list and discuss on the current anti- AGE therapies that are available.

Minor comments

1.Citation style in the text is uneven in few paragraphs (e.g.., in Sec 2)

2.Please add a list of abbreviations and their full forms in the manuscript.

Author Response

RESPONSE TO REVIEWERS

We deeply thank the editors and reviewers for their assessment of the manuscript. We have acted upon the recommendations of the reviewers in order to improve the manuscript quality. Below we added our point-by-point responses to each comment. In addition, we highlighted revisions in yellow in the updated manuscript.

 

REVIEWER 3:

 

In this review article, the authors Monterio-Alfredo et al., is providing an outline about the details regarding overall glycotoxin formation and their digestion in the gastrointestinal system.

The authors also focused on the intestinal absorption of the glycotoxins. The overall review emphasizes on the harmful effects caused by the advanced glycation end products (AGEs)and the major target molecules that might be involved in the AGE metabolism which may affect the homeostasis and prompt the onset of several metabolic and immunological diseases. The authors suggests that, identifying the molecules to prevent the absorption of AGEs would reduce the harmful effects of AGEs.

 

We deeply thank the reviewer for the comments made by the reviewer and the careful reading of the manuscript. As mentioned in the response to reviewer #2, this manuscript is included in a series of invited review articles focusing on different aspects of dietary sugars and AGEs with 3000 words limit. Thus, we have changed some aspects according to the following comments but we didn’t move away too much from our initial topic. Otherwise, there would be an overlap with the subject of other of the invited reviews.

 

Comments

1.The overall focus of the review is clear.

Thank you for the comment.

2.In the introduction, the authors mentioned that the AGEs have been associated with the insulin resistance in the obese models. It would be more informative if the authors could also specify the type of animal model (rat or mouse model etc.) that was used in the cited study.

Thank you for the comment, it was not only one study, in fact it was a general observation resulting from the combined observations in several models. Some information was included as well as a clarification in the reference used, a review article fully dedicated to this topic.

 

3.The authors stated that AGEs may be cleared by Amadoriases. Could the authors add few sentences explaining the amadoriases?

This information was included.

 

4.Are there any approaches for the quantification of AGEs? If there are any, can the authors include them in this review in a subsection.

This information was included in the section “Dietary AGEs bioavailability”

 

 

5. Can the authors list and discuss on the current anti-AGE therapies that are available.

This information was included in the section “Inhibition of AGEs intestinal absorption”. However, the information included is speculative for future studies since there are very scarce reports about the scavenging effects of known molecules over dietary glycotoxins in the gut.

 

Minor comments

1.Citation style in the text is uneven in few paragraphs (e.g.., in Sec 2)

Corrected.

 

2.Please add a list of abbreviations and their full forms in the manuscript.

Included.

Round 2

Reviewer 2 Report

The authors have addressed the majority of my concerns.