Association of Bitter Taste Receptor T2R38 Polymorphisms, Oral Microbiota, and Rheumatoid Arthritis
, Robert J. Schroth 1,2,4, Prashen Chelikani 1,2,*,† and Carol A. Hitchon 5,*,†Round 1
Reviewer 1 Report
The article titled: “Association of bitter taste receptor T2R38 polymorphisms, oral microbiota and rheumatoid arthritis” may be of interest to readers.
The standard of English grammar and comprehension is good.
The authors data and statistics discovered a difference between the bateriome composition between RA and non-RA controls, but not between the TAS2R38 genotypes of other groups.
My Comments are very minor to improve the quality of the article, as follows:
Title
- Acceptable
Abstract
- The authors did not investigate “Disrupted oral mucosal immunity and 36 T2R dependent host-microbial interactions may contribute to the association between RA and oral health.” I suggest a more appropriate conclusion be: “Subjects with RA suffer differences in their bacteriome composition, but there was no differences in TAS2R28 genotypes, further research is needed to understand the impact of RA and the effects of other genotypes on oral health.”
Introduction
- Acceptable
Results
- Acceptable, the images are clear.
Discussion
- Page 10, lines 262 to 269. I am not persuaded about that polymorphisms in TAS2R38 had an effect on the composition of buccal microbiota, because it is likely a confounding effect of RA. See the data which showed no difference in TAS2R28 genotypes. I suggest limiting the conclusion to fit with the actual results, therefore, please consider repeating my suggested abstract conclusion to replace this text.
Materials and Methods
- The authors need to explain with the text that they obtained subject written informed consent, or from guardians if the patient was unable to consent, from each subject to allow their medical records to be examined, and for the collection of buccal samples, following an ethical approval from Manitoba institutional review board (IRB).
References
- Acceptable
Author Response
We very much appreciate the feedback. Thank-you for the suggestions. We have addressed each of the comments raised in the revised manuscript and also discussed them point by point below.
My Comments are very minor to improve the quality of the article, as follows:
Title
- Acceptable
Abstract
- The authors did not investigate “Disrupted oral mucosal immunity and 36 T2R dependent host-microbial interactions may contribute to the association between RA and oral health.” I suggest a more appropriate conclusion be: “Subjects with RA suffer differences in their bacteriome composition, but there was no differences in TAS2R28 genotypes, further research is needed to understand the impact of RA and the effects of other genotypes on oral health.”
We recognize that based on our results it is not possible to conclude that disrupted oral mucosal immunity may contribute to the association between RA and oral health. Therefore, we have changed the conclusion of the abstract, as follows:
“These findings suggest an association between T2R38 polymorphisms and RA buccal microbial composition. However, further research is needed to understand the impact of T2R38 in oral health and RA development.”
Introduction
- Acceptable
Results
- Acceptable, the images are clear.
Discussion
- Page 10, lines 262 to 269. I am not persuaded about that polymorphisms in TAS2R38 had an effect on the composition of buccal microbiota, because it is likely a confounding effect of RA. See the data which showed no difference in TAS2R28 genotypes. I suggest limiting the conclusion to fit with the actual results, therefore, please consider repeating my suggested abstract conclusion to replace this text.
In order to control for the confounding effect of RA in the buccal microbial composition, we stratified the data by RA status, and we observed significant differences in the buccal bacteriome of individuals with different TAS2R38 genotypes both in the RA group as well as in the Non-RA group, which suggests that TAS2R38 may be associated with the buccal microbial composition.
As we discussed in the manuscript, the small sample size may be responsible for the lack of statistically significant differences in the TAS2R38 genotypes between RA and Non-RA groups. There was a notable, though not statistically significant,10% increased prevalence of PAV/PAV genotype in the RA population (42.9%) compared to Non-RA controls (32.8%). However, we recognize that our findings can only suggest an association between TAS2R38 polymorphisms and the buccal bacteriome in RA, and that future studies are needed to understand the impact of TAS2R38 on RA and oral health. Therefore, the updated conclusion (page 10, lines 272-278) reads as follows:
“In this study we show evidence that polymorphisms in TAS2R38 may be associated with differences in the microbial composition of the buccal mucosa in RA. However, replication in larger populations with paired periodontal exams and biosamples are needed to confirm the associations described.”
Materials and Methods
- The authors need to explain with the text that they obtained subject written informed consent, or from guardians if the patient was unable to consent, from each subject to allow their medical records to be examined and for the collection of buccal samples, following an ethical approval from Manitoba institutional review board (IRB).
The last paragraph of the Materials and Methods section describes the information about the Research Ethics approval as indicated below. Participants provided written informed consent to participate in the study including a limited chart review for laboratory measures, completion of questionnaires addressing arthritis, health habits and having a physician conducted joint exam. The statement has been modified as follows:
“The study was conducted according to the guidelines of the Declaration of Helsinki. The study protocol was approved by the University of Manitoba`s Health Research Ethics Board (HREB # HS15191 – B2001:070). All participants provided written informed consent to participate in this study, including limited medical chart review and collection of oral samples.”
References
- Acceptable
Reviewer 2 Report
Dear Authors,
In order to improve your article, I suggest you the following minor and major revisions:
In introduction I suggest to implement with the definition of the periodontitis and RA, in order to provide a mechanical explanation of why the identified correlation between polymorphism and microbic profile is involved in pathogenesis of RA in discussion section.
Please modify the p value in lowercase font in the caption of figure 1 and 4.
Along the text, please check space errors.
Best Regards
Author Response
REVIEWER 2:
We very much appreciate the feedback. Thank-you for the suggestions. We have addressed each of the comments raised in the revised manuscript and also discussed them point by point below.
Dear Authors,
In order to improve your article, I suggest you the following minor and major revisions:
In introduction I suggest to implement with the definition of the periodontitis and RA, in order to provide a mechanical explanation of why the identified correlation between polymorphism and microbic profile is involved in pathogenesis of RA in discussion section.
-Thank you very much for your suggestions. We appreciate the feedback. The manuscript has been revised and your suggestions have been incorporated.
-The definitions of periodontal disease and RA have been added to the introduction on pages 1 and 2 lines 48-53, as follows:
“RA is a chronic autoimmune disease characterized by joint inflammation that damages articular structures (bone and cartilage) leading to functional impairment. While the cause or trigger to develop RA remains unknown, genetic and environmental risks factors, including smoking and PD, are believed to play important roles. Periodontitis is a chronic inflammatory disease in which dysregulated immune responses against oral microbes lead to loss of periodontal tissues and subsequently tooth loss if left untreated.”
We have also added recent studies from our team that investigated the role of T2Rs in the oral innate immune responses on page 2 lines 60 and 74-75.
Please modify the p value in lowercase font in the caption of figure 1 and 4.
-This has been corrected in the caption of figures 1, 3 and 4.
Along the text, please check space errors.
-The manuscript has been revised and the space errors have been corrected.
Round 2
Reviewer 2 Report
Dear Authors,
Thank you for the revisions.
Some minor revisions are still present, such as:
p in capital letter in the caption of figure 1
a page is completely empty and figure 3 is shifted downward
Thank you
Best Regards
