The Interaction between the Oral Microbiome and Systemic Diseases: A Narrative Review

Round 1

Reviewer 1 Report (Previous Reviewer 1)

In this revised manuscript, the authors addressed some concerns of the previous reviewers. However, there seems to have been an oversight into teh seriousness of the review process, where there are inconsistencies in addressing the reviewer requests are present. There do not appear to be any statements addressing points 2 or 4 from Reviewer 1. Point 3 was given one additional sentence - which should be expanded upon. The use of italicization in scientific genus/species has not been addressed thoroughly. Overall, while there are plenty of correlations between microbiota and disease described, the authors never really give any clinical precautions or self-care recommendations, as they specify... is the aim of this review?

Lines 172-174, 398: Italicization of bacterial nomenclature still not consistent: : Staphylococcus aureus, Candida species, Lactobacilli, Candida albicans

Line 379: "Sistemyc Lupus Eritematosus" - In English language, I've only seen it spelled as "Systemic Lupus Erythematosus" - is this perhaps a spelling from another language?

Line 468 : I would argue LPS and peptidoglycan be specified as "endotoxins", or even "pro-inflammatory molecules". These don't fit the definition of "toxins".

Line 535 citation missing?

Author Response

Dear reviewer
the changes you requested have been made.
Best regards

Reviewer 2 Report (New Reviewer)

The review, the interaction between the oral microbiome and systemic diseases, has conducted a narrative review of oral microbiome and systematic diseases.

In my opinion, for a regular narrative review, there is no Materials and Methods or Results sections. Those two sections are usually presented in systematic review. However, there is some journals that require those two sections. Please follow the author guideline of Microbiol. Res.

The major problem of this manuscript is as follows:

1. The novelty is relatively somewhat not adequate. 

2. The manuscript is not well organized. The contents in each section do not follow a certain logic description.

3. In review article, the main section should be discussed in depth. However, this review understates the contents.

Fine

Author Response

The manuscript has been revisioned in according to the suggestions.

1)The review, the interaction between the oral microbiome and systemic diseases, has conducted a narrative review of oral microbiome and systematic diseases.

In my opinion, for a regular narrative review, there is no Materials and Methods or Results sections. Those two sections are usually presented in systematic review. However, there is some journals that require those two sections. Please follow the author guideline of Microbiol. Res.

1) The structure of review has been modified as  author guideline of Microbiol. Res.in an Abstract, Keywords, Introduction, Relevant Sections, Discussion, Conclusions with a suggested minimum word count of 4000 words.

2) The novelty is relatively somewhat not adequate. 

2) While it is true that the novelty is relatively somewhat inadequate, it is also true that there are no reviews that describe together all the pathologies that have been described here.

Furthermore, very innovative and important clinical precautions for the clinician are given. (section 3.4)

3). The manuscript is not well organized. The contents in each section do not follow a certain logic description.

3)The organization has been modified

4) In review article, the main section should be discussed in depth. However, this review understates the contents.

4) The  organization has been modified  and the most important section has been expanded, in particular the clinical considerations

Round 2

Reviewer 2 Report (New Reviewer)

All the issues have been addressed.

This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.

Round 1

Reviewer 1 Report

The manuscript "The interaction between the oral microbiome and systemic diseases: a narrative review" presents a summation of the field in regards to oral microbiome and its impacts on a number of relevant systemic diseases; namely, oral disease, diabetes, systemic lupus erythematosus (SLE), rheumatoid arthritis, cancer, alzheimers, and cardiovascular disease. While being a narrative review covering a specific focus, it was extremely informative and well referenced. A broad coverage of the topics is a strength of the manuscript. One suggested improvement that could be made is that certain topics might be explored a bit further, as they seem to be either glossed over or not covered. This includes a few topics such as 1) evidence of the ties of the oral microbiome to that of the gut 2) the challenges and current state of technology for assessing microbiomes, and 3) influence of factors on oral microbiome including tobacco use, alcohol, etc and 4) influence of probiotic and antibiotic on microbiome in treatment of disease. Minor criticisms include an inconsistent use of italics in genus and species names and a few minor grammar edits detailed below by line number.

Line 194: can the color complexes be explained a bit further for those unfamiliar with them?

Line 228: "... it was found in the peri-implant sites." The word "it" seems to be misplaced or unnecessary.

Line 601: Consider revising sentence due to grammatical errors and unclear message.

Reviewer 2 Report

This manuscript discusses a very broad topic, the microbiome and systemic diseases, the reason that is chosen not to make it a systematic review. This is not a problem and this type of papers are important as an overview and didactical reasons. But this paper fails in that aspect. The structure is somewhat chaotic and I found several mistakes, which makes me  mistrusting towards the information.

Line 43. The biofilm….. offering important benefits for the health and general well-being of the host. Please give an example how the oral microbiome does that.

Line 53.  The virulence factors of oral bacteria can reach distant organs. Please give an example.

Line 83. Presents è present

Line 86. The purpose of this narrative ….. Please carefully look at the grammar, I don’t understand the sentence.

Line 92 and (describe) any clinical precautions

Line 123 please correctly use bacterial names. Genus capital, species not, names Italic. After the first time Genus abbreviate as a letter. Streptococcus salivarius à S.salivarius

Line 127-129 Both the example and reference are wrong. The reference is about the interaction between S.gordonii, not S.salivarius, with Actinomyces spp. This interaction is co-aggregation, a direct binding between the two species, and is independent of sucrose. The paper that is given in the reference is a review, please refer to the original research.

Line 168-168. ..mice lacking oral microorganisms had a higher incidence of immune disorders. The reference that is given ‘Smoking cessation on periodontal and peri-implant health status: a systematic review’

Line 190 Crevicular Lactoferrin… Don’t use capital letters. Lactoferrin is not an inflammatory mediater, but a marker of inflammation.

Line 230. This line is an introduction for the next chapter, not the last Alinea of chapter 4.3.3.

Line 279. Furthermore, ther is no consensus as to whether type 1 diabetes(T1DM) causes bacterial changes specific to type 2 diabetes. I don’t understand this sentence.

Please use abbreviation consequently. After the first introduction (T1DM and T2DM) use the abbreviations. In the next sentence diabetes mellitus is written fully.

Line 352.. an increased presence of obligate anaerobic bacteria that exploit the absence of oxygen to promote inflammation. Awkward sentence, how is something that is absent be exploited.

Chapter 4.6 oral microbiota and cancer repeats a lot of the earlier information and writes a lot about periodontitis and even sucrose. As if this chapter is written separately.

Line 510. LPS and peptidoglycans are not pathogens, but toxins.

Line 520. Changes in the oral microbiome, for example due to a Western diet,… Nasidze et al. 2009  (DOI: 10.1101/gr.084616.108 ) investigated 120 individuals from 12 locations all over the world, but found little area-dependent differences.

Line 526 I don’t understand what DHA and fish consumption have to do with the oral microbiome related to Alzheimer’s. The is the case for anthocyanins.

Line 567 The authors forget to write that nitrate is converted to nitrous oxide which lowers blood pressure.

The use of English language is correct, but please check for minor spelling errors.