Title: Supplemental bifid triple viable capsule treatment improves inflammatory response and
T cell frequency in ulcerative colitis patients
Version: 0 Date: 22 Feb 2021
Reviewer's report:
In this study, UC patients with mild to moderate disease were treated with mesalazine
combined with somatostatin without (n=65) or with bifid triple viable capsules (n=65) during
2 months. Assessment of treatment was performed by comparing pro-inflammatory markers,
T cell frequencies, intestinal barrier markers and the IBDQ questionnaire at baseline to end of
treatment. Results show good efficacy for both treatment arms, but with better response in the
bifid triple viable capsule arm. It is an interesting study on an important topic.
Major comments:
1. When comparing different treatments you have to analyze if the groups differ in relation to
their change. It is not enough to compare baseline levels and end of treatment levels between
the two groups. You need to calculate the change between end of treatment and beginning of
treatment and find the p-value for the change in the experimental group vs the change in the
control group. This has to be performed for all analyses in Table 2-5.
2. The introduction is missing information about the bifid triple viable capsules. You need to
include information concerning what they are and some information from their use in other
studies. This will put your study into context.
3. The discussion needs to be totally re-written and made shorter. Currently it is more like a long
introduction with results reported. The results are not at all discussed. For example, the first 2
pages are more or less introduction and each section starts with a long introduction followed
by a re-cap of the results. Discussion about mechanisms of why the bifid triple viable capsules
improve treatment effects are missing. What might be the mechanism? How come they are so
much better? What have others done concerning probiotics? Does it affect the microbiota over
time, etc.
4. A large drawback of this study is that there is no placebo for the bifid triple viable capsules.
The authors need to discuss why they did not use a placebo and how this may have affected their
results. Also, was the clinician performing the endoscopies before and after treatment blinded
to the treatment the patient received?
5. The authors should also comment on compliance of taking the bifid triple viable capsules.
Did any patients report that they missed taking their capsules?
Minor comments:
1. In the abstract, a background is missing (there is only an aim) and there is no information in
the methods of how long time the treatments were given and how often the capsules were taken.
2. ET and DA0 should be spelled out in the abstract.
3. Background line 2, I am confused about “or even the colon” which is the same as large intestine
that was already mentioned. I suggest you just remove this.
4. Background line 4 “is extremely difficult to cure” needs to be rephrased, so far it is not possible
to cure UC, it can be treated but not cured. Or is it treated you mean?
5. Background lines 12-14, there are indeed several good treatments for UC and you mention
some. I suggest that you also add newer therapies, such as biologics.
6. I do not understand this sentence in the background: Yang Xiaoping [5] and colleagues
confirmed that the number of probiotics in the intestines of patients with ulcerative colitis was
significantly lower than that of normal subjects. - Number of probiotics? Do you mean number
of bacteria? I could not retrieve the reference so I had no chance of finding to what you refer.
7. Methods, first section (All patients and their families...): to what extent did the families
participate?
8. Inclusion and exclusion criteria: Since all patients had mild or moderate disease at inclusion,
I am wondering if severe disease was an exclusion criterion. This needs to be made clear. If so,
why were they excluded?
9. Methods, treatment regimen: was somatostatin given more than once during the study period.
This is unclear.
10. Since you have not looked at function of T cells I suggest you use “T cell frequency”
instead of immune function (everywhere in the manuscript, also in the title). Also, concerning
the intestinal mucosal barrier function, it should be re-phrased to “markers for intestinal mucosal
barrier function”.
11. Table 1: Maybe use “Baseline...” or “Before treatment...” instead of “General...” in the title.
12. Table 1: for some of the data it is impossible to have #2 values (where you have quantitative
data). This should be a t-value. On the other hand, it is not needed to show #2 / t values when
you show the p-value, but that is a matter of taste.
13. Table 1: What is “Course of disease (h)”? Is h = hours? I do not understand.
14. Table 1: Is mild and moderate degree of disease related to Mayo Score? This should be
explained.
15. Table 1: I am missing what types of treatment the patients were taking at baseline and how
long ago they were diagnosed with UC. This should be added.
Title: Supplemental bifid triple viable capsule treatment improves inflammatory response and
T cell frequency in ulcerative colitis patients
Version: 0 Date: 22 Feb 2021
Reviewer's report:
In this study, UC patients with mild to moderate disease were treated with mesalazine
combined with somatostatin without (n=65) or with bifid triple viable capsules (n=65) during
2 months. Assessment of treatment was performed by comparing pro-inflammatory markers,
T cell frequencies, intestinal barrier markers and the IBDQ questionnaire at baseline to end of
treatment. Results show good efficacy for both treatment arms, but with better response in the
bifid triple viable capsule arm. It is an interesting study on an important topic.
Major comments:
1. When comparing different treatments you have to analyze if the groups differ in relation to
their change. It is not enough to compare baseline levels and end of treatment levels between
the two groups. You need to calculate the change between end of treatment and beginning of
treatment and find the p-value for the change in the experimental group vs the change in the
control group. This has to be performed for all analyses in Table 2-5.
2. The introduction is missing information about the bifid triple viable capsules. You need to
include information concerning what they are and some information from their use in other
studies. This will put your study into context.
3. The discussion needs to be totally re-written and made shorter. Currently it is more like a long
introduction with results reported. The results are not at all discussed. For example, the first 2
pages are more or less introduction and each section starts with a long introduction followed
by a re-cap of the results. Discussion about mechanisms of why the bifid triple viable capsules
improve treatment effects are missing. What might be the mechanism? How come they are so
much better? What have others done concerning probiotics? Does it affect the microbiota over
time, etc.
4. A large drawback of this study is that there is no placebo for the bifid triple viable capsules.
The authors need to discuss why they did not use a placebo and how this may have affected their
results. Also, was the clinician performing the endoscopies before and after treatment blinded
to the treatment the patient received?
5. The authors should also comment on compliance of taking the bifid triple viable capsules.
Did any patients report that they missed taking their capsules?
Minor comments:
1. In the abstract, a background is missing (there is only an aim) and there is no information in
the methods of how long time the treatments were given and how often the capsules were taken.
2. ET and DA0 should be spelled out in the abstract.
3. Background line 2, I am confused about “or even the colon” which is the same as large intestine
that was already mentioned. I suggest you just remove this.
4. Background line 4 “is extremely difficult to cure” needs to be rephrased, so far it is not possible
to cure UC, it can be treated but not cured. Or is it treated you mean?
5. Background lines 12-14, there are indeed several good treatments for UC and you mention
some. I suggest that you also add newer therapies, such as biologics.
6. I do not understand this sentence in the background: Yang Xiaoping [5] and colleagues
confirmed that the number of probiotics in the intestines of patients with ulcerative colitis was
significantly lower than that of normal subjects. - Number of probiotics? Do you mean number
of bacteria? I could not retrieve the reference so I had no chance of finding to what you refer.
7. Methods, first section (All patients and their families...): to what extent did the families
participate?
8. Inclusion and exclusion criteria: Since all patients had mild or moderate disease at inclusion,
I am wondering if severe disease was an exclusion criterion. This needs to be made clear. If so,
why were they excluded?
9. Methods, treatment regimen: was somatostatin given more than once during the study period.
This is unclear.
10. Since you have not looked at function of T cells I suggest you use “T cell frequency”
instead of immune function (everywhere in the manuscript, also in the title). Also, concerning
the intestinal mucosal barrier function, it should be re-phrased to “markers for intestinal mucosal
barrier function”.
11. Table 1: Maybe use “Baseline...” or “Before treatment...” instead of “General...” in the title.
12. Table 1: for some of the data it is impossible to have #2 values (where you have quantitative
data). This should be a t-value. On the other hand, it is not needed to show #2 / t values when
you show the p-value, but that is a matter of taste.
13. Table 1: What is “Course of disease (h)”? Is h = hours? I do not understand.
14. Table 1: Is mild and moderate degree of disease related to Mayo Score? This should be
explained.
15. Table 1: I am missing what types of treatment the patients were taking at baseline and how
long ago they were diagnosed with UC. This should be added.
Please review this paper.
user
Title: Supplemental bifid triple viable capsule treatment improves inflammatory response and
T cell frequency in ulcerative colitis patients
Version: 0 Date: 22 Feb 2021
Reviewer's report:
In this study, UC patients with mild to moderate disease were treated with mesalazine
combined with somatostatin without (n=65) or with bifid triple viable capsules (n=65) during
2 months. Assessment of treatment was performed by comparing pro-inflammatory markers,
T cell frequencies, intestinal barrier markers and the IBDQ questionnaire at baseline to end of
treatment. Results show good efficacy for both treatment arms, but with better response in the
bifid triple viable capsule arm. It is an interesting study on an important topic.
Major comments:
1. When comparing different treatments you have to analyze if the groups differ in relation to
their change. It is not enough to compare baseline levels and end of treatment levels between
the two groups. You need to calculate the change between end of treatment and beginning of
treatment and find the p-value for the change in the experimental group vs the change in the
control group. This has to be performed for all analyses in Table 2-5.
2. The introduction is missing information about the bifid triple viable capsules. You need to
include information concerning what they are and some information from their use in other
studies. This will put your study into context.
3. The discussion needs to be totally re-written and made shorter. Currently it is more like a long
introduction with results reported. The results are not at all discussed. For example, the first 2
pages are more or less introduction and each section starts with a long introduction followed
by a re-cap of the results. Discussion about mechanisms of why the bifid triple viable capsules
improve treatment effects are missing. What might be the mechanism? How come they are so
much better? What have others done concerning probiotics? Does it affect the microbiota over
time, etc.
4. A large drawback of this study is that there is no placebo for the bifid triple viable capsules.
The authors need to discuss why they did not use a placebo and how this may have affected their
results. Also, was the clinician performing the endoscopies before and after treatment blinded
to the treatment the patient received?
5. The authors should also comment on compliance of taking the bifid triple viable capsules.
Did any patients report that they missed taking their capsules?
Minor comments:
1. In the abstract, a background is missing (there is only an aim) and there is no information in
the methods of how long time the treatments were given and how often the capsules were taken.
2. ET and DA0 should be spelled out in the abstract.
3. Background line 2, I am confused about “or even the colon” which is the same as large intestine
that was already mentioned. I suggest you just remove this.
4. Background line 4 “is extremely difficult to cure” needs to be rephrased, so far it is not possible
to cure UC, it can be treated but not cured. Or is it treated you mean?
5. Background lines 12-14, there are indeed several good treatments for UC and you mention
some. I suggest that you also add newer therapies, such as biologics.
6. I do not understand this sentence in the background: Yang Xiaoping [5] and colleagues
confirmed that the number of probiotics in the intestines of patients with ulcerative colitis was
significantly lower than that of normal subjects. - Number of probiotics? Do you mean number
of bacteria? I could not retrieve the reference so I had no chance of finding to what you refer.
7. Methods, first section (All patients and their families...): to what extent did the families
participate?
8. Inclusion and exclusion criteria: Since all patients had mild or moderate disease at inclusion,
I am wondering if severe disease was an exclusion criterion. This needs to be made clear. If so,
why were they excluded?
9. Methods, treatment regimen: was somatostatin given more than once during the study period.
This is unclear.
10. Since you have not looked at function of T cells I suggest you use “T cell frequency”
instead of immune function (everywhere in the manuscript, also in the title). Also, concerning
the intestinal mucosal barrier function, it should be re-phrased to “markers for intestinal mucosal
barrier function”.
11. Table 1: Maybe use “Baseline...” or “Before treatment...” instead of “General...” in the title.
12. Table 1: for some of the data it is impossible to have #2 values (where you have quantitative
data). This should be a t-value. On the other hand, it is not needed to show #2 / t values when
you show the p-value, but that is a matter of taste.
13. Table 1: What is “Course of disease (h)”? Is h = hours? I do not understand.
14. Table 1: Is mild and moderate degree of disease related to Mayo Score? This should be
explained.
15. Table 1: I am missing what types of treatment the patients were taking at baseline and how
long ago they were diagnosed with UC. This should be added.
assistant