Title: Assessing the Relationship Between Gut Microbiota and Irritable bowel syndrome: a
Two- Sample Mendelian Randomization Analysis
Version: 0 Date: 28 Mar 2023
Reviewer's report:
I read with great interest the manuscript by Liu et al., a Mendelian Randomization study designed
to examine the casual association between gut microbiome and irritable bowel syndrome. The
manuscript is well written and here are some comments for revision.
Experimental design and methods
The method section  lacks sufficient details in certain aspects, which may affect the readability
of the article as well as the reproducibility of the experimental results. For example,
1. The formulae used to calculate the proportion of variation explained (R2) and F-statistics:
a) What are the meanings of the parameters "MAF", "n" and "k" in the two equations and how
to obtain them?
b) When excluding the SNPs, it would be good to calculate the F-value again.
2. The beta values obtained from the results are relatively small. This could potentially be due
to the calculation unit used in the Mibiogen database.
3. For the MR design, Outcome Data Sources, Selection of Instrumental Variables and statistical
analyses, authors should justified their rationales behind the selection of each method used. For
example,
a) The Mibiogen database includes approximately 4,000 individuals who do not have European
ancestry. It would be worthwhile to investigate whether this non-European population has any
impact on the findings. A previous study has figured out this problem (PMID: 36380372).
b) I suggest to provide an explanation of the reasons behind selecting a specific method. This
will help readers understand the rationale for the approaches.
Validity of the findings.
In the discussion, the authors mentioned that "a decrease of phylum Actinobacteria was found in
patients with IBS compared to healthy controls"; however, phylum Actinobacteria was identified
as a risk factor in this study (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.02, 1.15; P
= 0.011). This elaboration may be contradictory.
Considering the modest #-value and nominal p-value, the biological interpretation of the results
should be elaborated.
Additional Comments
Line 65: some unexpected spaces at the end of paragraph;
Attention should be paid to the font used for writing Latin.
Table 4: OR calculated via MR-Egger method was very large.
Title: Assessing the Relationship Between Gut Microbiota and Irritable bowel syndrome: a
Two- Sample Mendelian Randomization Analysis
Version: 0 Date: 28 Mar 2023
Reviewer's report:
I read with great interest the manuscript by Liu et al., a Mendelian Randomization study designed
to examine the casual association between gut microbiome and irritable bowel syndrome. The
manuscript is well written and here are some comments for revision.
Experimental design and methods
The method section  lacks sufficient details in certain aspects, which may affect the readability
of the article as well as the reproducibility of the experimental results. For example,
1. The formulae used to calculate the proportion of variation explained (R2) and F-statistics:
a) What are the meanings of the parameters "MAF", "n" and "k" in the two equations and how
to obtain them?
b) When excluding the SNPs, it would be good to calculate the F-value again.
2. The beta values obtained from the results are relatively small. This could potentially be due
to the calculation unit used in the Mibiogen database.
3. For the MR design, Outcome Data Sources, Selection of Instrumental Variables and statistical
analyses, authors should justified their rationales behind the selection of each method used. For
example,
a) The Mibiogen database includes approximately 4,000 individuals who do not have European
ancestry. It would be worthwhile to investigate whether this non-European population has any
impact on the findings. A previous study has figured out this problem (PMID: 36380372).
b) I suggest to provide an explanation of the reasons behind selecting a specific method. This
will help readers understand the rationale for the approaches.
Validity of the findings.
In the discussion, the authors mentioned that "a decrease of phylum Actinobacteria was found in
patients with IBS compared to healthy controls"; however, phylum Actinobacteria was identified
as a risk factor in this study (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.02, 1.15; P
= 0.011). This elaboration may be contradictory.
Considering the modest #-value and nominal p-value, the biological interpretation of the results
should be elaborated.
Additional Comments
Line 65: some unexpected spaces at the end of paragraph;
Attention should be paid to the font used for writing Latin.
Table 4: OR calculated via MR-Egger method was very large.
Please review this paper.
user
Title: Assessing the Relationship Between Gut Microbiota and Irritable bowel syndrome: a
Two- Sample Mendelian Randomization Analysis
Version: 0 Date: 28 Mar 2023
Reviewer's report:
I read with great interest the manuscript by Liu et al., a Mendelian Randomization study designed
to examine the casual association between gut microbiome and irritable bowel syndrome. The
manuscript is well written and here are some comments for revision.
Experimental design and methods
The method section  lacks sufficient details in certain aspects, which may affect the readability
of the article as well as the reproducibility of the experimental results. For example,
1. The formulae used to calculate the proportion of variation explained (R2) and F-statistics:
a) What are the meanings of the parameters "MAF", "n" and "k" in the two equations and how
to obtain them?
b) When excluding the SNPs, it would be good to calculate the F-value again.
2. The beta values obtained from the results are relatively small. This could potentially be due
to the calculation unit used in the Mibiogen database.
3. For the MR design, Outcome Data Sources, Selection of Instrumental Variables and statistical
analyses, authors should justified their rationales behind the selection of each method used. For
example,
a) The Mibiogen database includes approximately 4,000 individuals who do not have European
ancestry. It would be worthwhile to investigate whether this non-European population has any
impact on the findings. A previous study has figured out this problem (PMID: 36380372).
b) I suggest to provide an explanation of the reasons behind selecting a specific method. This
will help readers understand the rationale for the approaches.
Validity of the findings.
In the discussion, the authors mentioned that "a decrease of phylum Actinobacteria was found in
patients with IBS compared to healthy controls"; however, phylum Actinobacteria was identified
as a risk factor in this study (odds ratio (OR): 1.08; 95% confidence interval (CI): 1.02, 1.15; P
= 0.011). This elaboration may be contradictory.
Considering the modest #-value and nominal p-value, the biological interpretation of the results
should be elaborated.
Additional Comments
Line 65: some unexpected spaces at the end of paragraph;
Attention should be paid to the font used for writing Latin.
Table 4: OR calculated via MR-Egger method was very large.
assistant