The Impact of Maternal Chronic Inflammatory Conditions on Breast Milk Composition: Possible Influence on Offspring Metabolic Programming

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The article is highly comprehensive and thorough in its content. The English language is clear, the text is professionally accurate, and the terminology aligns well with the scientific context. The references are precisely integrated into the argumentation. The structure of the content is logical, and the subsections are distinctly separated. Have the authors investigated how maternal dietary habits (e.g., high-fat diets, etc) influence the lipid composition of breast milk? The article mentions that breastfeeding has a lipid-lowering effect but does not elaborate on how this might affect the mother’s long-term cardiovascular risk. Expanding on this aspect would be beneficial. The article highlights the role of microRNAs, but it is not entirely clear to what extent these are responsible for the long-term health outcomes of the offspring. Could more specific examples be provided in this regard? Is there any data available on how breast milk lipid and microRNA composition varies across different populations and geographic regions? The article is highly promising and valuable, and I recommend it for publication. The references (more than 190) are relevant, and the plagiarism index of the article is low.

Author Response

Answers to Revisor 1:

We are very grateful for your invaluable comments and suggestions, which make our work more understandable.

1. Have the authors investigated how maternal dietary habits (e.g., high-fat diets, etc) influence the lipid composition of breast milk?

Thank you for your valuable suggestion. We have incorporated an extension to section 1, where lines 120 to 156 in the manuscript are exposed to what you asked for, with 24 new references.

2. The article mentions that breastfeeding has a lipid-lowering effect but does not elaborate on how this might affect the mother’s long-term cardiovascular risk. Expanding on this aspect would be beneficial.

Thank you for the observation. A small paragraph regarding this information was added to the manuscript between lines 349 and 358.

3. The article highlights the role of microRNAs, but it is not entirely clear to what extent these are responsible for the long-term health outcomes of the offspring. Could more specific examples be provided in this regard?

Thank you for the suggestion. Little information is available regarding the question, but one original study was included in the manuscript; please go to lines 545 to 548.

4. Is there any data available on how breast milk lipid and microRNA composition varies across different populations and geographic regions?

Regarding this question, a paragraph was added in the first section of the manuscript between lines 157 to 189.

In total, 34 new references were added to the manuscript to resolve all the suggestions.

 

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Reviewer 2 Report

Comments and Suggestions for Authors

The aim of the review is to determine the effects of inflammatory conditions on the composition of breast milk. The topic of the article is interesting but the way it is presented, the review has certain limitations. Given the nature of the review, it would be interesting for the authors to indicate the criteria they used to select the studies included in the review. On what basis do they consider the articles to be valid for inclusion? Since the composition of breast milk is discussed, the authors should include a brief section describing the composition of breast milk, otherwise there is a lack of context. In general terms, there is a lack of numerical data throughout the review. Likewise, the data obtained from these studies are not presented correctly. A better presentation in the form of Tables and Figures is needed. The only table present is difficult to interpret.

Other comments:

The type of studies studied for this review is not very well indicated in the abstract. Nor are the results obtained in this review indicated. Does it really affect? ​​How does it affect? This is important because otherwise the abstract only presents what is going to be done but not the results and conclusions.

Line 26-37: This should really go in a methodology section after the introduction. Google Scholar is not a database, it is a search engine. The combinations of words used for the search are not clear, only single words are indicated. Please specify.

Line 128: Which pro-inflammatory omega 3 and omega 6 fatty acids?

In reality, as the Table is presented, it is very difficult to follow the data from the studies. With all the acronyms and the different studies, the differences are not very visual.

Author Response

Thank you for your valuable responses, including your comments and suggestions for making our revision more understandable.

In the following text are all the responses related to the observations done to our review.

1. Given the nature of the review, it would be interesting for the authors to indicate the criteria they used to select the studies included in the review. On what basis do they consider the articles to be valid for inclusion?

Thank you for your comment:

Studies were included if they provided quantitative information on the relationship between previously mentioned variables and if the articles were written in English idiom. Please go to lines 62-64 in the manuscript.

 

2. Since the composition of breast milk is discussed, the authors should include a brief section describing the composition of breast milk, otherwise there is a lack of context.

Regarding the suggested section on breast milk composition, you are right; thank you for your thoughtful comment. We have extended the first section, which previously, briefly, described this topic. You can find it in the manuscript between lines 96 to 119.

 

3. In general terms, there is a lack of numerical data throughout the review. Likewise, the data obtained from these studies are not presented correctly.

 

Concerning numerical data, these data in the measure of the possible were added mainly in the lipid section, because this is the information available in the literature. See in the manuscript lines 96 to 156, 3741 to 379.

 

Comments 5 and 12 are similar, so they are answered together.

4. A better presentation in the form of Tables and Figures is needed. The only table present is difficult to interpret/12. In reality, as the Table is presented, it is very difficult to follow the data from the studies. With all the acronyms and the different studies, the differences are not very visual.

The table we presented is now in a new version. We hope it is clearer and easier to interpret now. Please find it between lines 388 to 393.

The modifications done in the table are all highlighted in yellow for a better visualization.

Other comments:

5. The type of studies studied for this review is not very well indicated in the abstract.

Line 25 in the abstract resolves this issue.

 

6. Nor are the results obtained in this review indicated. Does it really affect? ​​How does it affect? This is important because otherwise the abstract only presents what is going to be done but not the results and conclusions.

 

Thank you for your comment. Lines 21 to 23 in the abstract section clearly show what you asked.

 

7. Line 26-37: This should really go in a methodology section after the introduction.

 

Thank you for your suggestion; a section on methodology was added to the manuscript; please go to lines 40 to 64 in the manuscript. In addition a small introduction was added as well, visit lines 29 to 38.

 

8. Google Scholar is not a database, it is a search engine.

Google Scholar was corrected as a search engine as recommended.

 

9. The combinations of words used for the search are not clear, only single words are indicated. Please specify.

Combination of words for the search was added to the methodology section as suggested, please go to lines 49 to 58 in the new version of the manuscript.

 

10. Line 128: Which pro-inflammatory omega 3 and omega 6 fatty acids?

According to Panagos et al., there are no changes in omega 6 fatty acids, specifically linoleic acid, gamma linoleic acid and arachidonic acid. On the other hand, omega 3 fatty acids were reduced (ALA, EPA, DPA, DHA); this is the reason why the ratio is altered. Here, we attach the results of that article.

PUFA n-6
18:2n-6 (linoleic acid)	16.6 (3.4)	17.0 (3.0)	0.74
18:3n-6 (gamma-linolenic acid)	0.16 (0.06)	0.16 (0.07)	0.91
20:4n-6 (AA)	0.5 (0.08)	0.5 (0.1)	0.7
PUFA n-3
18:3n-3 (ALA)	1.7 (0.6)	1.2 (0.3)	0.008*
20:5n-3 (EPA)	0.8 (0.04)	0.6 (0.03)	0.013*
22:5n-3 (DPA)	0.2 (0.03)	0.1 (0.05)	0.0025*
22:6n-3 (DHA)	0.3 (0.1)	0.2 (0.06)	0.001*

 

Regarding the other reference cited in our manuscript (Enstad S, 2021), concerning the altered ratio of omega 6/omega 3, this article measured polyunsaturated fatty acid, but it only declared the omega 6 and 3 ratios. Thus, they did not give the table with the fatty acid profile, and thus a specific detail of what is changing in breast milk in this regard. Therefore, we cannot tell if the alteration in the ratio is due to an increase in omega 6 or a decrease in omega 3 lipids in this specific article.

 

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The limitations of the article are the same as before. That said, the authors have made an effort to improve the article.