The Peripheral Kynurenine Pathway and Psychosomatic Comorbidity in Subjects with Morbid Obesity Undergoing Bariatric Surgery
Round 1
Reviewer 1 Report
The authors conducted a novel study that explored whether there was any link between the kynurenine pathway and psychosomatic complaints in obese patients, as well as KP changes before and after bariatric surgery in this patient population. This is a well written manuscript with clearly presented methodology and results; however, it requires a few corrections prior to being accepted for publication:
- Page 1, Introduction: the first sentence is redundant and should be removed from the manuscript.
- Page 3/13, Participants and Inclusion Criteria: even though you later in the text mention certain psychiatric disorders, it would be more appropriate to specify the exact psychiatric, but also somatic disorders, in this section.
- Page 4/13, please define the "HPLC". Also please change "Palo Alta" to "Palo Alto".
- Page 4/13, Results section: "men/women 116/25" does not match information provided in the Table 1. Please correct.
- Page 8/13, paragraph 3, Discussion section: you discuss the reduction of the levels of KP metabolites following bariatric surgery and further associate this finding as a result of reduced inflammation. One could assume that this would imply that fat may be a source of inflammation, however, there is arguing evidence. Consider reference such as Hagman et al; Metabolism. 2017 May;70:12-22. to mention this in your Discussion section.
- Page 9, paragraph 2. The sentence "Age was associated with a trend to an increase in the KP metabolites, which probably is unhealthy" needs revision in order to be meaningful.
- Page 9, Strengths and Limitations: percentage of females seems to be different than presented in Table 1. Please correct.
- Please double check for any spelling mistakes.
Author Response
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Reviewer 2 Report
This study was designed to explore the correlation between peripheral kynurenine pathway and psychosomatic comorbidity in subjects with morbid obesity undergoing bariatric surgery. They concluded that the peripheral kynurenine pathway seemed to be of minor importance for the psychosomatic comorbidity in subjects with morbid obesity. The downregulation of all KP metabolites after bariatric surgery in-dicated reduced inflammation. The QA/XA ratio seemed to be a marker of insulin sensitivity and favorable glucose control.
The topic seems very interesting. The major weakness of this study is that what was found is pure correlation analysis and the sample size is relative small. The results were not well presented. The overall quality of paper was not very high. This study does not significantly advance the knowledge in this field.
Author Response
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Reviewer 3 Report
The paper is interesting and is actual because of great interest in the kynurenin/trp pathways.
Neverthless i suggest a revision of the manuscript
The authors in the discussion start with "lack of clear associations between the KP and psychosomatic disorders" I am not expert and I would like to have some more details in the authors' hypothesis on this point, the questionair that is used for the estabilishing "pshycosomatic disorders" and/or the personal evaluation of this issue may play a confunding role in this sense.
Thus starting the discussion (and somehow the results) with a "non result" I think is not proper. I suggest to revise this point both in the result and also in the discussion. Furthermore the explanation of the observed "non corrreltions" are in my opinion not clear. "the pronounced metabolic disorders in subjects with morbid obesity, which affects the KP,
might have obscured the associations between KP and the psychosomatic disorders"- Please clarify which were the strong correlation that you observed and avoid to discuss the "non observable" it would be more clear for me.
The aim looks to be related to observation if thte KN patway is chanded in the patients subjeted to surgery for weight loss.
Main finding is "All KP-metabolites and their ratios were reduced after bariatric surgery" and as authors reported this informaion was previously observed in other studies. So please clarify novelty of your finidins.
Furthermore "After surgery, the reduced KA/Kyn and KA/QA ratios could indicate reduced exercise
and reduced neuroprotection, respectively, which did not fit the improved physical activity and mental health " this is not clear what you mean. ANd not clear how you interprete these finding
In fact at the end
"The results reveal the uncertain relations between clinical disorders and the KP metabolites." thus authors did not find any relevant correlation?
"The adjusted associations between the KP and variables assumed to interfere with the KP are interesting ": please reformulate, the sentence is an opinion can be interesting for some readers but not for other use another word
The overall manuscript so need careful revision of result a clear statement of the new finiding to explain novelty and findings compard to literature
Author Response
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Reviewer 4 Report
The metabolites of kynurenine pathway play an important role in a lot of various physiological and pathological processes. It is assumed that they participate in pathogeneses of many psychiatric or neurologic diseases. Therefore, the topic of this original article, which deals with a possible role of kynurenines in psychosomatic diseases of patients suffering from extreme obesity treated by bariatric surgery, is highly interesting and timely. I quest that this article can attract attention of neurologists, psychiatrists, internists, pharmacologists, and many other experts.
In general, the paper is well-written, and the text structure is logic. The experiments are well-planned. In the chapter Introduction, the authors deal with the tryptophan metabolism (serotonin and kynurenine pathways) and a role of the metabolites in the physiological and pathological processes in a human organism. In the last paragraph of this chapter, the investigation aims and hypotheses are clearly presented. In the further chapter, Materials and Methods, the subject selection, interventions, variables, the HPLC analytical method, and statistical evaluations are well-described.
The results are adequately presented and also discussed in the chapters of Results and Discussion. The authors present results in three tables. The important aspects are explained correctly. I especially appreciate the subchapter 4.1 Strength and Limitations due to serious evaluation of many result aspects, for example: reflections of the concentration of kynurenines in plasma and cerebrospinal fluid for psychosomatic symptoms.
The manuscript was prepared with professional care. Therefore, I found no serious errors or mistakes. The conclusions correspond with the experimental results.
Author Response
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Round 2
Reviewer 2 Report
This revised manuscript is not significantly improved. The conclusion that the peripheral kynurenine pathway seemed to be of minor importance for the psychosomatic comorbidity in subjects with morbid obesity is based on a pure correlation analysis with relative small sample size. This conclusion is not convincing. The conclusion might be different from this study if the sample size is increased with same study design like this one. The overall quality of paper was not very high. This study does not significantly advance the knowledge in this field.
Author Response
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Reviewer 3 Report
I thank the authors for all their responce and for making more clear their manuscript with explanation.
I appreciated your answer and the changes that were performed also on the basis of the other referee comments
I think thath in the present form the paper can be accepted
Author Response
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