Causal Effects of Gut Microbiota on Sleep-Related Phenotypes: A Two-Sample Mendelian Randomization Study
and Lei Zhang 1,2,3,*
Round 1
Reviewer 1 Report
I read the Manuscript "causal effects of gut microbiota on sleep-related phenotypes: a two-sample Mendelian randomization study" with great interest. This is a very hot and important topic.
The figures and tables were difficult to understand. Figure 3 has different colors and it was unclear if the colors have meaning. When listing sleep duration it was unclear if it is meant long duration or short duration. Same for chronotype. Are you referring to delayed or advance sleep phase, or both.
Quality of English language was good.
Author Response
Response to Reviewers
The authors would like to thank the reviewers for their helpful comments. We feel these comments have strengthened the manuscript considerably. The changes/revisions we made in the revised manuscript are highlighted in yellow color.
Reviewer #1:
I read the Manuscript "causal effects of gut microbiota on sleep-related phenotypes: a two-sample Mendelian randomization study" with great interest. This is a very hot and important topic.
Comments 1: The figures and tables were difficult to understand. Figure 3 has different colors and it was unclear if the colors have meaning.
Response: Thank you for your detailed review. We have revised the title and figure legend of the Figure 3 as well as clarified the meanings of the different colors in the revised manuscript reads: “Figure 3 Graphical summary of the gut microbiota causally associated with sleep phenotypes and their subordination at different taxonomic levels. The gut microbiota is arranged at the taxonomic levels of class, order, family, and genus. Red represents the β of the causal association is greater than 0, and blue represents the β of the causal association is less than 0. Sleep phenotypes are classified into three colors: purple represents circadian types, green represents sleep quality (including sleep duration and snoring), and orange represents abnormal sleep patterns.” (page 7, lines 129-134).
Comments 2: When listing sleep duration it was unclear if it is meant long duration or short duration. Same for chronotype. Are you referring to delayed or advance sleep phase, or both.
Response: Thank you for your review. We have provided relevant annotations for sleep phenotypes (including sleep duration, chronotype, etc.) in Table S12. In this study, sleep duration is treated as a continuous variable. When the ratio estimate, denoted as β, of a certain microbial population with sleep duration is greater than 0, it indicates that an increase in the abundance of that bacteria is associated with an increase in sleep duration and vice versa. Similarly, chronotype is a binary variable, with "morning preference" being assigned a value of 1 and "evening preference" assigned a value of 0. When the β is greater than 0, it suggests that an increase in the abundance of the bacteria is associated with a higher tendency towards morning preference and vice versa.
Author Response File: 
Author Response.doc
Reviewer 2 Report
Article: Causal effects of gut microbiota on sleep-related phenotypes: a two-sample Mendelian randomization study
Authors present a study investigating a currently popular topic, namely, the role of gut microbiota in regulating a seemingly disparate pathology. To accomplish this authors utilized Mendelian randomization to analyze/index different GWAS datasets: one GWAS data set relating to the abundance of human gut microbiome, and multiple GWAS data sets relating to sleep-related phenotypes. This study purportedly identifies several microbiota taxa that have "causal effect ... on sleep, and identified causal risk and protective taxa for chronotype, sleep duration, snoring and insomnia."
Suggestions:
Line 41: "Sleep is an essential physiological activity that takes up one-third of human life and is crucial to the proper functioning of the body. "
Citation(s) needed
Line 97: "The IVW method"
please define IVM acronym when first used
Line 111: Figure 2: This looks like a table not a figure; needs label(s) for line plots after "Number of SNPs" column. i.e. what is being shown?
Line 128: Figure 3. This figure just repeats results from Figure 2. Suggest delete.
Author Response
Response to Reviewers
The authors would like to thank the reviewers for their helpful comments. We feel these comments have strengthened the manuscript considerably. The changes/revisions we made in the revised manuscript are highlighted in yellow color.
Reviewer #2:
Authors present a study investigating a currently popular topic, namely, the role of gut microbiota in regulating a seemingly disparate pathology. To accomplish this authors utilized Mendelian randomization to analyze/index different GWAS datasets: one GWAS data set relating to the abundance of human gut microbiome, and multiple GWAS data sets relating to sleep-related phenotypes. This study purportedly identifies several microbiota taxa that have "causal effect ... on sleep, and identified causal risk and protective taxa for chronotype, sleep duration, snoring and insomnia."
Comments 1: Line 41: "Sleep is an essential physiological activity that takes up one-third of human life and is crucial to the proper functioning of the body. "
Citation(s) needed.
Response: Thank you for your detailed review. We added the citation in the page 1, line 42.
Comments 2: Line 97: "The IVW method"
Please define IVW acronym when first used.
Response: Thank you for your detailed review. We added the definition of the IVW acronym in the page 3, line 97.
Comments 3: Line 111: Figure 2: This looks like a table not a figure; needs label(s) for line plots after "Number of SNPs" column. i.e. what is being shown?
Response: Thank you for your suggestion. We have added the label “β [95% CI]” for forest plots and revised the title of Figure 2 as “Forest plot of causal effects of gut microbiota on sleep-related phenotypes.” (page 4, lines 112).
Comments 4: Line 128: Figure 3. This figure just repeats results from Figure 2. Suggest delete.
Response: Thank you for your review. Figure 3 provides a visual representation of the hierarchical relationship between gut microbiota at different species levels in the significant causal relationships, which is an additional information that Figure 2 lacks. The gut microbiota at different species levels have consistent causal effects on the same sleep phenotype, which further demonstrates the robustness of our results. Additionally, we revised the title and figure legend as: “Figure 3. Graphical summary of the gut microbiota causally associated with sleep phenotypes and their subordination at different taxonomic levels. The gut microbiota is arranged at the taxonomic levels of class, order, family, and genus. Red represents the β of the causal association is greater than 0, and blue represents the β of the causal association is less than 0. Sleep phenotypes are classified into three colors: purple represents circadian types, green represents sleep quality (including sleep duration and snoring), and orange represents abnormal sleep patterns.” (page 7, lines 129-134).
Author Response File: Author Response.doc
