Whole Genome Deep Sequencing of the Oral Microbiome in Epidermolysis Bullosa

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The topic is very interesting and the manuscript is very clear and well-written.

 

The authors present a thorough analysis of the microbiome whole genome deep

sequencing data obtained from three different patients with EB.

 

The fact that this analysis reveals a different set of predominant microbes present in each patient and as compared to the general population emphasizes the necessity for personalized treatment for patients with EB. However, the small number of samples analyzed is a drawback for a general conclusion to be made. Moreover, the specific type of EB of each patient is not mentioned or taken into account for this analysis.

 

The authors suggest that that the unique signature of microorganisms in patients with EB as compared to the normotypical population is likely related to their restricted nutrition which is rich in carbohydrates. This is a very important observation. Nevertheless, it is also likely that some similarities might come up if the analysis is performed in a larger population and the data are grouped and compared among individuals with the same subtype of EB.

 

My opinion is that the authors should refer and explain those limitations in the manuscript.

 

Comments for author File: Comments.pdf

Author Response

The authors present a thorough analysis of the microbiome whole genome deep

sequencing data obtained from three different patients with EB.

Thank you so very much for your kind comments.

The fact that this analysis reveals a different set of predominant microbes present in each patient and as compared to the general population emphasizes the necessity for personalized treatment for patients with EB. However, the small number of samples analyzed is a drawback for a general conclusion to be made. Moreover, the specific type of EB of each patient is not mentioned or taken into account for this analysis.

Due to the rare nature of the disease, we were hesitant to name a specific type, as this might raise privacy concerns. We are now certain that it should not be an issue. The manuscript has been edited to reflect the types of EB.

 

The authors suggest that that the unique signature of microorganisms in patients with EB as compared to the normotypical population is likely related to their restricted nutrition which is rich in carbohydrates. This is a very important observation. Nevertheless, it is also likely that some similarities might come up if the analysis is performed in a larger population and the data are grouped and compared among individuals with the same subtype of EB.

My opinion is that the authors should refer and explain those limitations in the manuscript.

 

Thank you again for your constructive comments. We have added more emphasis on the limitations, and explained in the manuscript that we are in the process of expanding the research after receiving funding.

Reviewer 2 Report

Comments and Suggestions for Authors

Dear Authors,

your pilot study on the altered microbiom in EB patients, in particular in the upper digestive truct, is a important contribution to improve the care of EB patients. Your paper shows a well organized study program, provdides helful figures and has a structured, well written test.

In sum, I recommend to publish this mansucript without revision 

Author Response

Dear Authors,

your pilot study on the altered microbiom in EB patients, in particular in the upper digestive truct, is a important contribution to improve the care of EB patients. Your paper shows a well organized study program, provdides helful figures and has a structured, well written test.

In sum, I recommend to publish this mansucript without revision 

 

Thank you so very much for your kind comments and suggestions. We have further refined the manuscript.

Reviewer 3 Report

Comments and Suggestions for Authors

Dear Authors,

The topic is relatively new especially concerning the oral microbiome in EB and the whole genome deep sequencing. As stated by parents of EB paediatric patients appropriate dental care is really difficult to be found and maintained.

I assent the title and the structure of the manuscript.

The illustrative material is exhaustive enough with numerous tables and figures.

I see the following limitations:

1. The clinical type of EB for the 3 patients is not defined
2. The number of patients is very small, only 3 individuals, and control group of healthy age/sex matched individuals is lacking compared to a previous study from 2022 where 77 RDEB children vs 27 healthy controls were studied (Korolenkova, 2022).

I would have the following suggestions:

1. Point out the clinical EB type and severity of the 3 patients
2. Compare with healthy individuals if possible
3. Cite Korolenkova 2022 in the reference list
4. Clearly state the limitations of the work.

Author Response

he topic is relatively new especially concerning the oral microbiome in EB and the whole genome deep sequencing. As stated by parents of EB paediatric patients appropriate dental care is really difficult to be found and maintained.

I assent the title and the structure of the manuscript.

The illustrative material is exhaustive enough with numerous tables and figures.

I see the following limitations:

1. The clinical type of EB for the 3 patients is not defined
2. The number of patients is very small, only 3 individuals, and control group of healthy age/sex matched individuals is lacking compared to a previous study from 2022 where 77 RDEB children vs 27 healthy controls were studied (Korolenkova, 2022).

I would have the following suggestions:

1. Point out the clinical EB type and severity of the 3 patients
2. Compare with healthy individuals if possible
3. Cite Korolenkova 2022 in the reference list
4. Clearly state the limitations of the work.

Thank you very much for your kind comments and suggestions. 

Our initial concern was the privacy of the individuals; however, we have now been assured that this is not a concern, so the specific genetic information has been added to the manuscript.

All the corrections have been made in red for easy comparison. The study concerning the MicroScan Walkaway was also included in the References and Discussion section.

All three patients had severe lesions, and 2 were Dystrophic EB, and one Col XVII JEB.

The database for Bristle includes the normative microbiome values for thousands of individuals of similar age. The results concentrated on the significantly different oral bacteria distinguishing the EB patients from the typical. Limitations and future research plans were also discussed. Whole-genome deep sequencing is relatively new and still more costly than previous methods; however, we hope to secure financial support for a larger clinical study. 

 

Thank you again for your kind comments and suggestions.