Reviewer ’s report  
 
Title: A randomized placebo -controlled clinical trial of a multi -strain probiotic formulation (Bio -
Kult®) in the management of diarrhea -predominant irritable bo wel syndrome  
 
Version: 0 Date: 13 Mar 2018  
 
Reviewer: Makoto Arai  
 
Reviewer's report:  
 
The authors showed the utility of Bio -Kult® for D -IBS patients by RCT study.  
I have some comments for this study.  
(1) The authors showed the change in severity and frequency of abdominal pain on the IBS -SSS 
as the endpoints of this study. The  authors should show their time points; at 1 month, at 4 
month or at 5 month. It is important to decide the timing to evaluate the effect of drug before 
the study started.  
 
(2) Is it true that all patients (181 in Bio -Kult and 179 in Placebo in Figure 1) co mpleted the 4 
months' treatment?  
 
(3) The information of clinical background is very poor.  
 
(4) The authors should show the sub -group analysis based on the information of clinical 
background.  
Are the methods appropriate a nd well described?  
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.  
 
Yes 
 
  
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify 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 manuscript:  
 
Needs some l anguage corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years receive d reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way ga in or lose  
financially from the publication of this manuscript, either now 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 sala ry from an organization that 
holds  or has applied for patents relating to 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 interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests' below.  
 
I agree to the open peer review policy of the  journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for 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 included as confidential comm ents 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: A randomized placebo -controlled clinical trial of a multi -strain probiotic formulation (Bio -
Kult®) in the management of diarrhea -predominant irritable bo wel syndrome  
 
Version: 0 Date: 13 Mar 2018  
 
Reviewer: Makoto Arai  
 
Reviewer's report:  
 
The authors showed the utility of Bio -Kult® for D -IBS patients by RCT study.  
I have some comments for this study.  
(1) The authors showed the change in severity and frequency of abdominal pain on the IBS -SSS 
as the endpoints of this study. The  authors should show their time points; at 1 month, at 4 
month or at 5 month. It is important to decide the timing to evaluate the effect of drug before 
the study started.  
 
(2) Is it true that all patients (181 in Bio -Kult and 179 in Placebo in Figure 1) co mpleted the 4 
months' treatment?  
 
(3) The information of clinical background is very poor.  
 
(4) The authors should show the sub -group analysis based on the information of clinical 
background.  
Are the methods appropriate a nd well described?  
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.  
 
Yes 
 
  
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify 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 manuscript:  
 
Needs some l anguage corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years receive d reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way ga in or lose  
financially from the publication of this manuscript, either now 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 sala ry from an organization that 
holds  or has applied for patents relating to 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 interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests' below.  
 
I agree to the open peer review policy of the  journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for 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 included as confidential comm ents 
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: A randomized placebo -controlled clinical trial of a multi -strain probiotic formulation (Bio -
Kult®) in the management of diarrhea -predominant irritable bo wel syndrome  
 
Version: 0 Date: 13 Mar 2018  
 
Reviewer: Makoto Arai  
 
Reviewer's report:  
 
The authors showed the utility of Bio -Kult® for D -IBS patients by RCT study.  
I have some comments for this study.  
(1) The authors showed the change in severity and frequency of abdominal pain on the IBS -SSS 
as the endpoints of this study. The  authors should show their time points; at 1 month, at 4 
month or at 5 month. It is important to decide the timing to evaluate the effect of drug before 
the study started.  
 
(2) Is it true that all patients (181 in Bio -Kult and 179 in Placebo in Figure 1) co mpleted the 4 
months' treatment?  
 
(3) The information of clinical background is very poor.  
 
(4) The authors should show the sub -group analysis based on the information of clinical 
background.  
Are the methods appropriate a nd well described?  
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.  
 
Yes 
 
  
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify 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 manuscript:  
 
Needs some l anguage corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years receive d reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way ga in or lose  
financially from the publication of this manuscript, either now 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 sala ry from an organization that 
holds  or has applied for patents relating to 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 interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests' below.  
 
I agree to the open peer review policy of the  journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for 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 included as confidential comm ents 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant