A Brief Review of Local Bacteriotherapy for Preventing Respiratory Infections
Round 1
Reviewer 1 Report
Ciprandi et have presented the manuscript Local bacteriotherapy for preventing respiratory infections.
This is mansuscript presents the argument for consideration for the application of good bacteria (probiotics?) as application as local bacteriotherapy for prevention of recurrent respiratory diseases.
This manuscript presents a compelling list of clinical trials demonstrating the benefit for applying two bacterial strains S. salivarius 24SMBC and S> oralis as the good bacteria.
Key comments:
- This article focusses heavily on these two good bacterial strains for respiratory infections. It does not acknowledge the application of other bacterial strains for this same applications so seems rather focused solely on these two strains. For example, there is significant evidence for other S. salivarius strains K12 and M18, with the former also used in respiratory infections. Other S. oralis, S. uberis and S. rattus strains have also been used in oral infections.
- Why not call these good bacteria probiotics? Be definition this is a “live bacteria which when given in adequate amounts confers a benefit to the consumer” WHO 2002. Isn’t this really what the live biotherapeutics are?
3- Live biotherapeutics implies a therapeutic application. Is that what is presented here? Or prevention? See probiotics above?
4- with such a list of clinical trials, surely a meta analysis would really help the argument for these strains here. - The article needs a “so what” at the end. With a long list of clinical trials what is the key message summed up to be delivered.
Specifics:
Article would help to have line numbers on side for a reviewer to inform location of errors “but here goes:
Page 1 Introduction line 1; “on the society” remove “the”
Page 1: third paragraph: “it is important TO attempt”. Add TO
Page 1 “early attending” should be “early attendance”
Page 1 last paragpraph: allergy should be allergies
Page 2: second paragraph: biofilm definition is inadequate/ Please re-define.
Page 2: Therefore using of good bacteria. Remove “of”
Page 2: Surely this is where we define probiotics in this third paragraph.
Page 2: “2” harbouring “in” organs should be “on” organs?
Page 2: Indeed it is known some bacteria…. Maybe rewrite this sentence:
Page 2: Consistently, should be “Consistent”
Page 3: … a primary BLIS. Should read “a primary BLIS producer”
Why is Local Bacteriotherapy in capital letters? also used as LB in the document. Please be consistent/
A "real life" study? What does this mean?
group A Streptococci should be Group A Streptococci (GAS). Elsewhere (page 4)in review is talks about group A beta haemolytic streptococci which are the same group. Needs to be consistent.
Page3-4 feels like the authors have just listed out the publications and added "some details". Also the relevance and grouping of these findings. as above, what about a meta analysis to help validate the reports?
References:
#12/13 are emboldened and indented. not consistent with the other references.
Table 1: Overall fine except for Outcomes of Treatment. Needs to be more specific./ What % of improvement and by when? compared to control? This columns is really the most interesting one to read so should really state the key findings.
Author Response
Answers to Reviewer 1
First of all, we would thank the Reviewer for the helpful comments and suggestions.
Ciprandi et have presented the manuscript Local bacteriotherapy for preventing respiratory infections.
This is mansuscript presents the argument for consideration for the application of good bacteria (probiotics?) as application as local bacteriotherapy for prevention of recurrent respiratory diseases.
This manuscript presents a compelling list of clinical trials demonstrating the benefit for applying two bacterial strains S. salivarius 24SMBC and S> oralis as the good bacteria.
Key comments:
- This article focusses heavily on these two good bacterial strains for respiratory infections. It does not acknowledge the application of other bacterial strains for this same applications so seems rather focused solely on these two strains. For example, there is significant evidence for other S. salivarius strains K12 and M18, with the former also used in respiratory infections. Other S. oralis, S. uberis and S. rattus strains have also been used in oral infections.
R Manty thanks for this comment. Actually, we did consider respiratory infections and not oral infections. In addition, there are no other product available for “local” route.
- Why not call these good bacteria probiotics? Be definition this is a “live bacteria which when given in adequate amounts confers a benefit to the consumer” WHO 2002. Isn’t this really what the live biotherapeutics are?
R Many thanks for this comment. We agree with You about this point, so we considered the term probiotic.
- Live biotherapeutics implies a therapeutic application. Is that what is presented here? Or prevention? See probiotics above?
R Many thanks for this question. Actually, the probiotic mixture is proposed for preventing respiratory infections and is marketed in some countries, including Italy.
- with such a list of clinical trials, surely a meta-analysis would really help the argument for these strains here.
R Surely, but it requires a specific analysis. We prepared a simple review on this topic. However, included this aspect in discussion.
- The article needs a “so what” at the end. With a long list of clinical trials what is the key message summed up to be delivered.
Many thanks for this comment. We added a final consideration.
Specifics:
Article would help to have line numbers on side for a reviewer to inform location of errors “but here goes:
Page 1 Introduction line 1; “on the society” remove “the”
R Amended
Page 1: third paragraph: “it is important TO attempt”. Add TO
R Amended
Page 1 “early attending” should be “early attendance”
R Amended
Page 1 last paragpraph: allergy should be allergies
R Amended
Page 2: second paragraph: biofilm definition is inadequate/ Please re-define.
R Amended
Page 2: Therefore using of good bacteria. Remove “of”
R Amended
Page 2: Surely this is where we define probiotics in this third paragraph.
R Amended
Page 2: “2” harbouring “in” organs should be “on” organs?
R Amended
Page 2: Indeed it is known some bacteria…. Maybe rewrite this sentence:
R Amended
Page 2: Consistently, should be “Consistent”
R Amended
Page 3: … a primary BLIS. Should read “a primary BLIS producer”
R Amended
Why is Local Bacteriotherapy in capital letters? also used as LB in the document. Please be consistent/
R We used the capital initials to emphasize this concept.
A "real life" study? What does this mean?
R Conducted in a setting reflecting the clinical practice.
group A Streptococci should be Group A Streptococci (GAS). Elsewhere (page 4)in review is talks about group A beta haemolytic streptococci which are the same group. Needs to be consistent.
R Amended
Page3-4 feels like the authors have just listed out the publications and added "some details". Also the relevance and grouping of these findings. as above, what about a meta analysis to help validate the reports?
R Many thanks for this criticism. We included in discussion this need.
References:
#12/13 are emboldened and indented. not consistent with the other references.
R Amended
Table 1: Overall fine except for Outcomes of Treatment. Needs to be more specific./ What % of improvement and by when? compared to control? This columns is really the most interesting one to read so should really state the key findings.
R Many thanks for this comment. We included this relevant information in two new columns (control and rate of improvement).
Reviewer 2 Report
The review Local bacteriotherapy for preventing respiratory infections is a paper covering a subject of great interest. Respiratory infections affect mainly children and the elder and trigger an economic burden on the medical system and society itself.
My first impression when reading the paper was a positive one, and my suggestions were to bring some improvements to the introduction, insert the title of Figure 1 near the figure and properly number the references.
However, a previous review on an almost identical subject was published by the same author in 2020, this work was not cited by the current review. Figure 1 and Table 1 from the current review are highly similar to the ones already published in 2020. Furthermore, all the references of the current review were also part of the previous one, no new references form the last two years were added.
Ciprandi G, La Mantia I, Damiani V, Passali D. Local Bacteriotherapy - a promising preventive tool in recurrent respiratory infections. Expert Rev Clin Immunol. 2020 Nov;16(11):1047-1052. doi: 10.1080/1744666X.2021.1833720. Epub 2020 Oct 15. PMID: 33022191.
Author Response
Answers to Reviewer 2
First of all, we would thank the Reviewer for the helpful comments and suggestions.
The review Local bacteriotherapy for preventing respiratory infections is a paper covering a subject of great interest. Respiratory infections affect mainly children and the elder and trigger an economic burden on the medical system and society itself.
My first impression when reading the paper was a positive one, and my suggestions were to bring some improvements to the introduction, insert the title of Figure 1 near the figure and properly number the references.
R We provided these corrections as suggested.
However, a previous review on an almost identical subject was published by the same author in 2020, this work was not cited by the current review. Figure 1 and Table 1 from the current review are highly similar to the ones already published in 2020. Furthermore, all the references of the current review were also part of the previous one, no new references form the last two years were added.
Ciprandi G, La Mantia I, Damiani V, Passali D. Local Bacteriotherapy - a promising preventive tool in recurrent respiratory infections. Expert Rev Clin Immunol. 2020 Nov;16(11):1047-1052. doi: 10.1080/1744666X.2021.1833720. Epub 2020 Oct 15. PMID: 33022191.
R Many thanks for this comment. Actually, in the revised version, we provided more interesting data in Table. In addition, we included some consideration considering the COVID era.
Reviewer 3 Report
Thank you for giving me the opportunity to peer review this studυ. Please indicate the following comments
A type 2 immunity presumes a consequential defect of type 1 immune response that contributes to fight infections. As a result, allergic subjects are prone to contract infections more frequently and severely than healthy subjects [16]. As proof of this mechanism, allergen-specific immunotherapy, restoring a normal balance between type 1 and 2 immunity, consequently, reduces predisposition to RI.
I suggest that this paragraph must be written more detailed. Also, the content of the N017 bibliographical reference does not mention that.
Local Bacteriotherapy: the evidence
In relation to paragraph and Table 1, an additional column should be added with the %rates, i.e. how many of the persons who received this Schedule had the outcome indicated in the table. It would also be good to add any side effects.
Author Response
Answers to Reviewer 3
First of all, we would thank the Reviewer for the helpful comments and suggestions.
Thank you for giving me the opportunity to peer review this studυ. Please indicate the following comments
A type 2 immunity presumes a consequential defect of type 1 immune response that contributes to fight infections. As a result, allergic subjects are prone to contract infections more frequently and severely than healthy subjects [16]. As proof of this mechanism, allergen-specific immunotherapy, restoring a normal balance between type 1 and 2 immunity, consequently, reduces predisposition to RI.
I suggest that this paragraph must be written more detailed. Also, the content of the N017 bibliographical reference does not mention that.
R Many thanks for this comment. Really, reference 17 was cited, but there was a problem about formatting. We added a sentence to better clarify the concept.
Local Bacteriotherapy: the evidence
In relation to paragraph and Table 1, an additional column should be added with the %rates, i.e. how many of the persons who received this Schedule had the outcome indicated in the table. It would also be good to add any side effects.
R Many thanks for this comment. We provided the requested information.
Round 2
Reviewer 2 Report
Dear Authors, thank you for providing the modifications.
