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The authors have responsed to the comments/suggestions of the reviewers well.
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1. No conclusion in the Abstract. Please check and make sure the paper is organized according to the guideline for authors.
2. It is better to avoid the term SZ patients. In general, "person first" language should be used, otherwise, the term would be stigmatizing and dehumanizing, This is a very basic language requirement.
3. In the introduction, it remains unclear why the authors focused on the correlation between symptom severity and altered gut microbiota.
4. The design is case-control study but it remains unclear how healthy controls were matched to the case group. Many essential methodological details are lacking. I suggest the authors to report their results according to the STROBE statement.
5. The majority of patients with SZ were receiving medication treatment. How to exclude the influence of medication on gut microbiota?
6. Demographic and clinical factors are also associated with symptom severity. Whether the association between gut microbiota and symptoms is independent of demographic and clinical factors needs to be further clarified with multiple linear regression analysis.
7. Although the paper is readable, the language needs to be edited.
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Li et al used 16S rRNA sequencing technology to analyze the gut microbial composition of patients with schizophrenia in South China with a relatively large sample size and an effective method. Reliable statistical methods were used to demonstrate differences in gut microbiota between patients and healthy controls. In addition, the authors analyzed the correlation and symptom severity between the genera of microbiota and significant changes in the relative abundance of the patients, and initially identified three genera related to the development of schizophrenia. However, some contents are insufficiently specified.
1) Why should the residuals of the relative abundance of the altered microbiota be used to calculate the correlation between the relative abundance and the severity of the symptom group?
2) Why was the p value used for calculating the relative number of phyla and genera of microbiota differences, but not the other p values?
3) The p-value in "Relationship with Clinical characteristics" should be clearly displayed, not just using values below 0.05.
Abstract:
1. In line 38-39” 82 SZ patients and 80 demographically matched normal controls (NCs)”. Demographic data included many variables, please point out which variables were matched in this study and you are supposed to describe in the method.
2. I wonder the reason that there was missing the conclusions and keyword in the abstract.
Introduction
1. The pathway of gut microbiota influence schizophrenia should be further discussed, especially inflammatory and metabolic pathways.
Method
1. Please describe the source of participants in normal control group. Additionally, the start time and end time of this study should be reported.
2. The “BMI:18-35 kg/m2” in the inclusion of normal control group was not appropriate. This item indicate that obesity participants would include the normal control group. But obesity participants would influence the characterization of gut microbiota in normal control group.
3. Constipation is a common symptom in patients with schizophrenia and common adverse event by using antipsychotics. So it should be addressed both in the exclusion of NCs and patients with schizophrenia.
Result
1. Though the mean levels of cholesterol, triglyceride and glucose in the SZ group were normal, it did’t mean all of included patients with schizophrenia were normal. So I wanted to know were there any metabolic abnormalities in included schizophrenia patients. If there were, it should be reported analysed. If there weren’t, the SZ sample of this study lack of representation. Because previous studies suggest that about 50% of patients treated
with APs develop metabolic complications.
Discussion
1. Antipsychotics are the cornerstone in the schizophrenia. In addition, antipsychotics–especially the second-generation, or "atypical" antipsychotics – can cause severe metabolic side effects such as obesity, dyslipidemia, and type 2 diabetes. And gut microbiota may act via metabolic pathway to influence the MGBs. Hence, the influence of the drug use between gut microbiota and schizophrenia should be discussed.
Table 1.
1.Please provide the data of history of taking medicine, history of smoking and drinking as the method described.
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