Reviewer’ s report
Title: Bile pigment in small-bowel water content may reflect bowel habits: a retrospective analysis
of a capsule endoscopy imaging series
Version: 0Date: 28 Feb 2020
Reviewer: Andrea Shin
Reviewer's report:
The study describes the results of a retrospective analysis of patients who underwent capsule
endoscopy. Images of previously acquired capsule studies were analyzed for color change. It issuggested by the authors that lightness of the small bowel water content was significantly brighterand darker for patients with constipation compared to patients with normal bowel habits,respectively. Authors have interpreted the findings to suggest that color and darkness of smallbowel water content may reflect bile pigments and that bile pigments within the small bowel maybe associated with bowel symptoms due to their potential correlation with bile acids. I found thisstudy to be intriguing. Although there are some significant limitations due to the indirectness ofthe study, there is some hypothesis-generating data. It appears to me that the authors haveadequately addressed the comments provided by previous reviewers. I have only a few additionalcomments for the authors to consider.
Major comments:
In this study, authors make several assumptions to support their interpretation of conclusions.Firstly, it is assumed that small bowel bile pigment concentration is an indirect assessment of fecalbile acid levels. As authors do not specifically measure fecal bile acid content, it would be wise to
revise or temper this interpretation. At the current state, the data is only able to show that color
differences in SBWC that MAY reflect bilirubin content that may correlate with bowel symptoms.Secondly, it is assumed that the technique that is described provides an accurate measurement ofbile pigment concentration. It is unclear to me whether this claim has been validated; this is thefirst step before introducing the potential relationship with fecal bile acids.Some patients with bile acid diarrhea may present with altered fecal bile acid ratios despite normaltotal fecal bile acid content. It is unclear how small bowel bile pigment concentration would bereasonably expected to correlate with alternations in the ratio of primary to secondary fecal bileacids.
Minor comments:
What kind of questionnaire was used to determine bowel patterns? How was the daily diary that iscited on page 10 administered?Were bile acid sequestrants among the excluded medications list?Were investigators responsible for image processing and analysis also blinded to patients' clinicalinformation?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes 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.
YesAre 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 furtherassessment in your comments to the editors.
Not relevant to this manuscriptQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain 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 salary 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.
Not applicatbleI 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 reportincluding 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 commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
Reviewer’ s report
Title: Bile pigment in small-bowel water content may reflect bowel habits: a retrospective analysis
of a capsule endoscopy imaging series
Version: 0Date: 28 Feb 2020
Reviewer: Andrea Shin
Reviewer's report:
The study describes the results of a retrospective analysis of patients who underwent capsule
endoscopy. Images of previously acquired capsule studies were analyzed for color change. It issuggested by the authors that lightness of the small bowel water content was significantly brighterand darker for patients with constipation compared to patients with normal bowel habits,respectively. Authors have interpreted the findings to suggest that color and darkness of smallbowel water content may reflect bile pigments and that bile pigments within the small bowel maybe associated with bowel symptoms due to their potential correlation with bile acids. I found thisstudy to be intriguing. Although there are some significant limitations due to the indirectness ofthe study, there is some hypothesis-generating data. It appears to me that the authors haveadequately addressed the comments provided by previous reviewers. I have only a few additionalcomments for the authors to consider.
Major comments:
In this study, authors make several assumptions to support their interpretation of conclusions.Firstly, it is assumed that small bowel bile pigment concentration is an indirect assessment of fecalbile acid levels. As authors do not specifically measure fecal bile acid content, it would be wise to
revise or temper this interpretation. At the current state, the data is only able to show that color
differences in SBWC that MAY reflect bilirubin content that may correlate with bowel symptoms.Secondly, it is assumed that the technique that is described provides an accurate measurement ofbile pigment concentration. It is unclear to me whether this claim has been validated; this is thefirst step before introducing the potential relationship with fecal bile acids.Some patients with bile acid diarrhea may present with altered fecal bile acid ratios despite normaltotal fecal bile acid content. It is unclear how small bowel bile pigment concentration would bereasonably expected to correlate with alternations in the ratio of primary to secondary fecal bileacids.
Minor comments:
What kind of questionnaire was used to determine bowel patterns? How was the daily diary that iscited on page 10 administered?Were bile acid sequestrants among the excluded medications list?Were investigators responsible for image processing and analysis also blinded to patients' clinicalinformation?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes 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.
YesAre 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 furtherassessment in your comments to the editors.
Not relevant to this manuscriptQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain 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 salary 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.
Not applicatbleI 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 reportincluding 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 commentsto 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: Bile pigment in small-bowel water content may reflect bowel habits: a retrospective analysis
of a capsule endoscopy imaging series
Version: 0Date: 28 Feb 2020
Reviewer: Andrea Shin
Reviewer's report:
The study describes the results of a retrospective analysis of patients who underwent capsule
endoscopy. Images of previously acquired capsule studies were analyzed for color change. It issuggested by the authors that lightness of the small bowel water content was significantly brighterand darker for patients with constipation compared to patients with normal bowel habits,respectively. Authors have interpreted the findings to suggest that color and darkness of smallbowel water content may reflect bile pigments and that bile pigments within the small bowel maybe associated with bowel symptoms due to their potential correlation with bile acids. I found thisstudy to be intriguing. Although there are some significant limitations due to the indirectness ofthe study, there is some hypothesis-generating data. It appears to me that the authors haveadequately addressed the comments provided by previous reviewers. I have only a few additionalcomments for the authors to consider.
Major comments:
In this study, authors make several assumptions to support their interpretation of conclusions.Firstly, it is assumed that small bowel bile pigment concentration is an indirect assessment of fecalbile acid levels. As authors do not specifically measure fecal bile acid content, it would be wise to
revise or temper this interpretation. At the current state, the data is only able to show that color
differences in SBWC that MAY reflect bilirubin content that may correlate with bowel symptoms.Secondly, it is assumed that the technique that is described provides an accurate measurement ofbile pigment concentration. It is unclear to me whether this claim has been validated; this is thefirst step before introducing the potential relationship with fecal bile acids.Some patients with bile acid diarrhea may present with altered fecal bile acid ratios despite normaltotal fecal bile acid content. It is unclear how small bowel bile pigment concentration would bereasonably expected to correlate with alternations in the ratio of primary to secondary fecal bileacids.
Minor comments:
What kind of questionnaire was used to determine bowel patterns? How was the daily diary that iscited on page 10 administered?Were bile acid sequestrants among the excluded medications list?Were investigators responsible for image processing and analysis also blinded to patients' clinicalinformation?
Are the methods appropriate and well described?
If not, please specify what is required in your comments to the authors.
YesDoes 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.
YesAre 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 furtherassessment in your comments to the editors.
Not relevant to this manuscriptQuality of written English
Please indicate the quality of language in the manuscript:
AcceptableDeclaration of competing interests
Please complete a declaration of competing interests, considering the following questions:
1. Have you in the past five years received reimbursements, fees, funding, or salary from an
organisation that may in any way gain or lose financially from the publication of thismanuscript, either now or in the future?
2. Do you hold any stocks or shares in an organisation that may in any way gain 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 salary 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.
Not applicatbleI 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 reportincluding 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 commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant