Unveiling the Impact of Lactic Acid Bacteria on Blood Lipid Regulation for Cardiovascular Health

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

It is important to include accurate data on the incidence of cardiovascular diseases at a global level.

Line 36. The reference lacks date.

Along the document, there are some mistakes in the reference format.

 

Please include more current references. There are some references with more than 10 years old.

Comments for author File: Comments.pdf

Author Response

Dear Reviewers,

Thank you so much for your valuable comments and explanations and your great suggestions. We have tried to edit our manuscript according to your revision. Corrections or modifications were marked in RED (Reviewer-1), GREEN (Reviewer-2) and BLUE (Reviewer-3) colour font throughout the manuscript. Also, you can find the corrections one by one below. We hope our manuscript is enhanced after your critical revision.

 

Thanks & Regards,

Corresponding author (on behalf of co-authors)

 

Reviewer-1

Dear reviewer,

Thank you very much for your valuable comments. We have carefully checked all of your comments and corrected them. Please find them below.

1. It is important to include accurate data on the incidence of cardiovascular diseases at a global level.

Thanks a lot for your suggestions. We have added this between lines 37-40.

2. Line 36. The reference lacks date.

Thanks a lot. We believe that our references had changed because of reference manager program after submission (We observed changes in terms of formatting). Hence, we updated all references in terms of format including those you pointed out.

3. Along the document, there are some mistakes in the reference format.

Thanks a lot for your comment. We fixed the mistakes ad updated the references as per the journal.

4. Please include more current references. There are some references with more than 10 years old.

Thank you for your suggestion. We added several references to the manuscript. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

I believe this review makes an acceptable effort, and its publication would be of interest, provided that certain key issues are addressed. My main concern is lack of in-depth consideration given to several important taxonomic aspects that play a role into the effectiveness of certain microorganisms in the regulation of lipids in the bloodstream. For example, the authors seem to attribute to the entire genus Lactobacillus these regulatory properties (lines 111-115, 255?), without considering that these are strain-dependent traits (that is, some strains possess these abilities whereas others lack it). Regarding this issue, I suggest that the authors search for Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66. Moreover, the authors should take into account the substantial modification that the genus Lactobacillus has recently undergone, which has resulted in the genus being split into 25 new genera (Zheng J, Wittouck S, Salvetti E, Franz CMAP, Harris HMB, Mattarelli P, O'Toole PW, Pot B, Vandamme P, Walter J, Watanabe K, Wuyts S, Felis GE, Gänzle MG, Lebeer S. A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020 Apr;70(4):2782-2858. doi: 10.1099/ijsem.0.004107. 

 

Minor suggestions:

Lines 78 and 79 are duplicated

Please, consider rephrasing line 88 or clarify

The figures are difficult to see due the small font size

line 198: in parenthesis only the year

Author Response

Reviewer-2

Dear reviewer,

Thank you very much for your valuable comments. We have carefully checked all of your comments and corrected them. Please find them below.

1. I believe this review makes an acceptable effort, and its publication would be of interest, provided that certain key issues are addressed. My main concern is lack of in-depth consideration given to several important taxonomic aspects that play a role into the effectiveness of certain microorganisms in the regulation of lipids in the bloodstream. For example, the authors seem to attribute to the entire genus Lactobacillus these regulatory properties (lines 111-115, 255?), without considering that these are strain-dependent traits (that is, some strains possess these abilities whereas others lack it). Regarding this issue, I suggest that the authors search for Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S, Calder PC, Sanders ME. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014 Aug;11(8):506-14. doi: 10.1038/nrgastro.2014.66.

Many thanks for your comment. We have edited the text in Lines 111-115 and 255 as well as when we saw it was necessary. Furthermore, we added some lines (57-64) from the reference that you suggested.

2. Moreover, the authors should take into account the substantial modification that the genus Lactobacillus has recently undergone, which has resulted in the genus being split into 25 new genera (Zheng J, Wittouck S, Salvetti E, Franz CMAP, Harris HMB, Mattarelli P, O'Toole PW, Pot B, Vandamme P, Walter J, Watanabe K, Wuyts S, Felis GE, Gänzle MG, Lebeer S. A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020 Apr;70(4):2782-2858. doi: 10.1099/ijsem.0.004107.

Many thanks for this important matter. We have utilized the mentioned paper while writing the manuscript. We revisited to make sure that we used the recent terminology.

Minor suggestions:

Lines 78 and 79 are duplicated

Thanks a lot. They are actually not duplicated. Hence, we did not make any changes here. 

“In another randomised controlled study in diabetic individuals, the change in the lipid profile of those who consumed milk fermented with probiotic bacteria (Streptococcus thermophiles, Lb. casei, Lb. acidophilus and Bifidobacterium lactis) and those who consumed traditional fermented milk (Streptococcus thermophiles and Lb. bulgaricus)”

Please, consider rephrasing line 88 or clarify.

Thanks a lot. It has been clarified.

The figures are difficult to see due the small font size

We have updated both figures and increased the font size.

line 198: in parenthesis only the year

Thanks a lot. As we created a new reference library, we fixed all typos/errors regarding the references.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors, 

I found the manuscript to be informative, but could benefit with a bit more supportive quantitative results. I have listed my comments below:

Line 25: Write the full word for HMG-CoA, then put the abbreviated form in brackets

Line 36: What is with the WHO citation? “n.d.-a, n.d.-b.?

Line 39: Spelling error, “infraction”.

Line 63: number of bacteria? Or concentration?

Line 96-107: Please fix the paragraph. Do not list points i, ii, and iii, in separate sentences.

Line 97: Define BHS, before using it its abbreviation.

Line 106: Fix citation.

Line 140-141: Can you describe the “chenodeoxycholic acid > lithocholic acid = deoxycholic acid > cholic acid”, can be a bit difficult to interpret as written.

Line 138-151: Minor grammatical errors throughout, needs to be checked over again.

Line 162: Grammar error, change to EPS may act as an inhibitor of ACE.

Line 174-206: This paragraph reads like a list of different study results combined together. I would reword this whole paragraph to make the flow better. Some of the citations are also in the wrong format. Table 1 is good, but the paragraph that describes Table 1 should be rewritten for flow and context.

Line 175: You mention changes to the lipid profile, could you provide quantitative numbers to support this review?

Line 208: Should be written as 156 overweight men and women”

Line 218: Define PPARa

Line 255-256: Clumped references again. Could you individually state which reference is responsible for? Or provide the highlights of their study then provide the citation.

Line 278-280: Please double-check that the latest nomenclature is used.

Line 336: Spelling error, probiotic.

General comments: Please avoid clumping your citations. It is easier and better if you individually provide a citation for each statement so that it is easier to find the relevant reference. Also fix the formatting of the in-text references.

General comments: Please review spelling, grammar, and spacing throughout the manuscript (e.g., put a space before inserting reference/citation in text).

General Comments: You mention the health benefits for LAB organisms, but could you elaborate on the concentration of LAB required in the diet to elicit these health promoting effects? For example, what was the dosage for some of the animal/human studies?

 

General Comments: I would suggest including some quantitative findings into the review paper to provide more support on the benefits of LAB. As of right now, a lot of the citations used from other studies sound repeated (e.g., This study did this and found this result, that study did a similar investigation and found this result). I would suggest including some quantitative data to support those citations as well (e.g., could be included as a table or figure).

Comments on the Quality of English Language

Comments regarding the quality of the English Language is included in my above comments.

Author Response

Reviewer-3

Dear reviewer,

Thank you very much for your valuable comments. We have carefully checked all of your comments and corrected them. Please find them below.

Dear authors, 

I found the manuscript to be informative, but could benefit with a bit more supportive quantitative result. I have listed my comments below:

Line 25: Write the full word for HMG-CoA, then put the abbreviated form in brackets

Thank you, it was added.

Line 36: What is with the WHO citation? “n.d.-a, n.d.-b.?

Thanks a lot. The references were corrected. We believe that some modification happened after/during submission due to reference manager. Therefore, we checked all refences one by one and created a new library. We hope that now the references are all corrected. However, if we have missed something, we will do our best to fix it.

Line 39: Spelling error, “infraction”.

Thank you. It was corrected.

Line 63: number of bacteria? Or concentration?

It was changed to bacteria concentration.

Line 96-107: Please fix the paragraph. Do not list points i, ii, and iii, in separate sentences.

Thanks a lot for suggestion. It was corrected.

Line 97: Define BHS, before using it its abbreviation.

It was added.

Line 106: Fix citation.

The citation was fixed.

Line 140-141: Can you describe the “chenodeoxycholic acid > lithocholic acid = deoxycholic acid > cholic acid”, can be a bit difficult to interpret as written.

Thank you, you are right. We revised it as “Endogenous bile acids, such as chenodeoxycholic acid, lithocholic acid, deoxycholic acid, and cholic acid, activate FXR to varying degrees, with conjugated forms showing reduced effectiveness compared to their unconjugated counterparts”.

Line 138-151: Minor grammatical errors throughout, needs to be checked over again.

It was checked and edited.

Line 162: Grammar error, change to EPS may act as an inhibitor of ACE.

We are sorry for that. It has been corrected.

Line 174-206: This paragraph reads like a list of different study results combined together. I would reword this whole paragraph to make the flow better. Some of the citations are also in the wrong format. Table 1 is good, but the paragraph that describes Table 1 should be rewritten for flow and context.

Thank you for your comment. The citation formats were re-arranged. The paragraph was revised according to your comments.

Line 175: You mention changes to the lipid profile, could you provide quantitative numbers to support this review?

Thank you so much. As you mentioned, increase and decrease status has been added. But in the paragraph below and in the table 1, there are already details of the references given together.

 

Line 208: Should be written as 156 overweight men and women”

It was corrected.

Line 218: Define PPARa

Peroxisome proliferator activated receptor alpha (PPARα) was added.

Line 255-256: Clumped references again. Could you individually state which reference is responsible for? Or provide the highlights of their study then provide the citation.

The references in the sentence have been edited to only 2 review references.

Line 278-280: Please double-check that the latest nomenclature is used.

Thanks a lot. We have used the latest one utilizing from the following paper: A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae.

Line 336: Spelling error, probiotic.

Thanks a lot. It was corrected.

General comments: Please avoid clumping your citations. It is easier and better if you individually provide a citation for each statement so that it is easier to find the relevant reference. Also fix the formatting of the in-text references.

Thanks a lot. We have corrected all references in the text as we created a new library and we hope that the document you would be downloading will have the same format as we submit. Regarding clumping citations, in fact, the fine details of the references you mentioned as clustering are in the paragraph. When we give a general view or want to summarize many studies, we have to provide several citations. However, we go in details and cite references separately to make it easier for the readers.

General comments: Please review spelling, grammar, and spacing throughout the manuscript (e.g., put a space before inserting reference/citation in text).

All of them were revised according to your comments.

General Comments: You mention the health benefits for LAB organisms, but could you elaborate on the concentration of LAB required in the diet to elicit these health promoting effects? For example, what was the dosage for some of the animal/human studies?

 In human studies, we have included dosages in the tables if they were specified in the studies.

General Comments: I would suggest including some quantitative findings into the review paper to provide more support on the benefits of LAB. As of right now, a lot of the citations used from other studies sound repeated (e.g., This study did this and found this result, that study did a similar investigation and found this result). I would suggest including some quantitative data to support those citations as well (e.g., could be included as a table or figure).

Thanks a lot. We have added quantitative findings to where they were relevant. You may please check between lines 193-228. Since we have already given these findings in tables, we did not create a separate table for that.

 

 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have checked and properly edited the text, and the key issues were addressed. I recommend the publication of the manuscript in its present form.