The Relationship between the Infant Gut Microbiota and Allergy. The Role of Bifidobacterium breve and Prebiotic Oligosaccharides in the Activation of Anti-Allergic Mechanisms in Early Life

Round 1

Reviewer 1 Report

I would like to thank the authors for the manuscript. Please, kindly check my comments attach

Comments for author File: Comments.pdf

Author Response

We would like to thank the Reviewer for the revision of our manuscript that helped us to improve the manuscript. Below please find our response to questions or comments:

1. According to the recommendation the introduction and the section 2 has been summarized, and the age of infants was added when it was possible. Due to the fact that the title was modified (according to the recommendations of the second reviewer) it was impossible to drastically shorten these sections, but they were significantly shortened.
2. According to the recommendation the new tables (Table 1 and Table 2) are added (line 109, and line 120). Table 1 contains data on the effect of antibiotics used in the prenatal period and early postnatal period (up to 3 years of age) on the composition of the intestinal microbiota. Table 2 contains data on the impact of antibiotic exposure on the risk of wheezing and asthma. However, other allergic diseases such as hay fever, eczema, food allergy have not been included in the Table 2 due to the fact that studies analyzing these diseases were subject to a meta-analysis published in 2018 (in total 34 studies). The revised manuscript discusses the meta-analysis results in more details (lines 111-118)
3. We agree that the Figure 1 was too superficially mentioned in the text. At present, Figure 1 is moved and more deeply described (lines 184-201)
4. The paragraph between lines 270-276 in “old” manuscript, which was a repetition of the idea described in the introduction, in the revised manuscript was removed from the introduction section and now is only in section 3 (lines 177-181)
5. According the suggestion in section 5.2 – the mechanism of activation the immune response in preterm newborn with NEC and LOS by Bifidobacterium breve was discussed (lines 287-302)
6. Figure 2 in the corrected manuscript has been removed.
7. According to the suggestion – we have tried to describe the possible relation of maltodextrin and B. breve. As there is no studies in this filed - it is rather hypothesis but presented (lines 338-347)

We also want to emphasize that the manuscript was edited by a professional translator (and a certificate is attached).

All minor comments have been taken into account.

Thank you for all comments, and words about “great ideas” – all these ideas remained unchanged.

Reviewer 2 Report

This is a nice well-written summary of an important topic. It is in fact a review of the literature rather than new information so revising the title in that regard would be helpful. It is also a rather poorly disguised attempt at marketing in infant formula without adequate disclosure of the funding relationship between the company trying to market the formula and the authors. This problem could be easily solved by making the appropriate disclosure, or by eliminating section 6.1 and changing the title to something like "The Relationship Between The Infant Microbiome And Allergy, A Review Of The Literature"

Author Response

We would like to thank the Reviewer for the revision of our manuscript that helped us to improve the manuscript. Below please find our response to comments:

1. According to the recommendation the title of the manuscript was changed. However, we decided to include in the title information that the manuscript is not so much a review of the literature on the impact of microbiota on allergic diseases, but is primarily focused on the importance of bifidobacteria, with particular regard to Bifidobacterium breve as a part of microbiota activated anti-allergic processes.
2. According to the recommendation to avoid the relationship between the authors and the companies, the sections 6.1 and 6.2 were eliminated from the corrected manuscript and the section 6 was changed (lines 326-380), and according to the recommendation the Reviewer 2 some novel information was added (lines 338-347).
3. In addition in the section “Conflict of interest” (line 395)- it is now clearly emphasized that the first author (B.C.) conducts lectures sponsored by various companies. However, the current review has not been made in consultation with any companies, but is part of a project funded by the Children's Memorial Health Institute (the principal investigator - B.C.), as highlighted in section “Funding” (line 393).

Round 2

Reviewer 1 Report

Thank you for the corrections at this manuscript. In my opinion it has been improved. No more concerns of my side.