Reviewer ’s report  
 
Title: Small intestinal microbiota composition and the prog nosis of infants with ileostomy 
resulting from distinct primary diseases  
 
Version: 1 Date: 05 Jan 2020  
 
Reviewer's report:  
 
In this manuscript, Qian et al. describe small -intestinal (SI) microbiota profiles of neonates with 
SI ostomy due to various etiologies. The authors report a generally low microbial diversity in this 
patient population with a high variation o f profiles between individuals, which suggests an 
immature microbiome that is still unstable. Further, they report an effect of breast feeding on the 
abundance of several genera (i.e. Bifidobacteria, Streptococcus, Veillonella), which is associated 
with fa vorable clinical outcomes (i.e. body weight increase, lower incidence of colitis and 
sepsis).  
 
Overall the study is exploratory, highly descriptive and presents a rather limited set of 
computational analyses. Nonetheless, the scarcity of previous studies o f neonatal SI microbiota 
and the difficulty in recruiting a sufficiently large number of neonates with SI ostomies have to 
be acknowledged. Therefore, the presented data are sufficiently novel to warrant publication.  
 
Major concerns:  
 
1. The authors claim t hat their cluster analysis (Fig. 2) reveals that "patients were grouped 
according to the composition of genera" (lines 130 -131). It is unclear what this refers to. A 
potential clustering of different disease types (i.e. H, M or N) is not backed by the pres ented 
data, which show almost random clustering of the different disease types. It would be important 
that the authors clarify this. As a minor point, the figure may benefit from a color -blind -friendly 
color scale.  
 
2. As one of their key claims, the author s state that rates of colitis and sepsis were 
significantly lower in the breast -feeding group than in the formula group (lines 145 -147). 
However, they critically fail to provide results of statistical testing in Table 2 or the main text. 
Which statistical tests were used? How was significance determined? The same issues apply to 
the apparent increase in Bifidobacteria and Streptococcus. How was the type 1 error rate 
controlled for this?  
 
3. It is very difficult to understand the figures, which lack adequate descriptions. It would 
be helpful if the authors could provide more detailed figure legends. Specifically, Fig. 3 is 
confusing. What do the arrows in panel A indicate? The abbreviations are not explained. Is panel 
B really demonstrating the influence of en vironmental variables on samples (see line 329) or 
does it show clustering by disease type? How can the variance explained - as shown in the axis 
labels - be the same for panels A and B which show different analyses?  
 
 
 
Are the methods appropriate and well desc ribed?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may  in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either n ow or in the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating t o the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing int erests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the ma nuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Small intestinal microbiota composition and the prog nosis of infants with ileostomy 
resulting from distinct primary diseases  
 
Version: 1 Date: 05 Jan 2020  
 
Reviewer's report:  
 
In this manuscript, Qian et al. describe small -intestinal (SI) microbiota profiles of neonates with 
SI ostomy due to various etiologies. The authors report a generally low microbial diversity in this 
patient population with a high variation o f profiles between individuals, which suggests an 
immature microbiome that is still unstable. Further, they report an effect of breast feeding on the 
abundance of several genera (i.e. Bifidobacteria, Streptococcus, Veillonella), which is associated 
with fa vorable clinical outcomes (i.e. body weight increase, lower incidence of colitis and 
sepsis).  
 
Overall the study is exploratory, highly descriptive and presents a rather limited set of 
computational analyses. Nonetheless, the scarcity of previous studies o f neonatal SI microbiota 
and the difficulty in recruiting a sufficiently large number of neonates with SI ostomies have to 
be acknowledged. Therefore, the presented data are sufficiently novel to warrant publication.  
 
Major concerns:  
 
1. The authors claim t hat their cluster analysis (Fig. 2) reveals that "patients were grouped 
according to the composition of genera" (lines 130 -131). It is unclear what this refers to. A 
potential clustering of different disease types (i.e. H, M or N) is not backed by the pres ented 
data, which show almost random clustering of the different disease types. It would be important 
that the authors clarify this. As a minor point, the figure may benefit from a color -blind -friendly 
color scale.  
 
2. As one of their key claims, the author s state that rates of colitis and sepsis were 
significantly lower in the breast -feeding group than in the formula group (lines 145 -147). 
However, they critically fail to provide results of statistical testing in Table 2 or the main text. 
Which statistical tests were used? How was significance determined? The same issues apply to 
the apparent increase in Bifidobacteria and Streptococcus. How was the type 1 error rate 
controlled for this?  
 
3. It is very difficult to understand the figures, which lack adequate descriptions. It would 
be helpful if the authors could provide more detailed figure legends. Specifically, Fig. 3 is 
confusing. What do the arrows in panel A indicate? The abbreviations are not explained. Is panel 
B really demonstrating the influence of en vironmental variables on samples (see line 329) or 
does it show clustering by disease type? How can the variance explained - as shown in the axis 
labels - be the same for panels A and B which show different analyses?  
 
 
 
Are the methods appropriate and well desc ribed?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may  in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either n ow or in the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating t o the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing int erests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the ma nuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Small intestinal microbiota composition and the prog nosis of infants with ileostomy 
resulting from distinct primary diseases  
 
Version: 1 Date: 05 Jan 2020  
 
Reviewer's report:  
 
In this manuscript, Qian et al. describe small -intestinal (SI) microbiota profiles of neonates with 
SI ostomy due to various etiologies. The authors report a generally low microbial diversity in this 
patient population with a high variation o f profiles between individuals, which suggests an 
immature microbiome that is still unstable. Further, they report an effect of breast feeding on the 
abundance of several genera (i.e. Bifidobacteria, Streptococcus, Veillonella), which is associated 
with fa vorable clinical outcomes (i.e. body weight increase, lower incidence of colitis and 
sepsis).  
 
Overall the study is exploratory, highly descriptive and presents a rather limited set of 
computational analyses. Nonetheless, the scarcity of previous studies o f neonatal SI microbiota 
and the difficulty in recruiting a sufficiently large number of neonates with SI ostomies have to 
be acknowledged. Therefore, the presented data are sufficiently novel to warrant publication.  
 
Major concerns:  
 
1. The authors claim t hat their cluster analysis (Fig. 2) reveals that "patients were grouped 
according to the composition of genera" (lines 130 -131). It is unclear what this refers to. A 
potential clustering of different disease types (i.e. H, M or N) is not backed by the pres ented 
data, which show almost random clustering of the different disease types. It would be important 
that the authors clarify this. As a minor point, the figure may benefit from a color -blind -friendly 
color scale.  
 
2. As one of their key claims, the author s state that rates of colitis and sepsis were 
significantly lower in the breast -feeding group than in the formula group (lines 145 -147). 
However, they critically fail to provide results of statistical testing in Table 2 or the main text. 
Which statistical tests were used? How was significance determined? The same issues apply to 
the apparent increase in Bifidobacteria and Streptococcus. How was the type 1 error rate 
controlled for this?  
 
3. It is very difficult to understand the figures, which lack adequate descriptions. It would 
be helpful if the authors could provide more detailed figure legends. Specifically, Fig. 3 is 
confusing. What do the arrows in panel A indicate? The abbreviations are not explained. Is panel 
B really demonstrating the influence of en vironmental variables on samples (see line 329) or 
does it show clustering by disease type? How can the variance explained - as shown in the axis 
labels - be the same for panels A and B which show different analyses?  
 
 
 
Are the methods appropriate and well desc ribed?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may  in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation t hat may in any way gain or lose 
financially from the publication of this manuscript, either n ow or in the future?  
 
3. Do you hold or are you currently applying for any patents  relating to the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating t o the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing int erests' 
below. If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the ma nuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant