Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This paper reports a case where Tannerella forsythia, a periodontal pathogen, was detected for the first time in the synovial fluid of patients with osteoarthritis (OA), which is of certain innovation and clinical significance.
Only by using PCR to detect DNA, it is impossible to distinguish between live bacteria and dead bacteria.
2. In the acknowledgments section, the author mentioned using Chat GPT for translation assistance. Some of the sentence structures are a bit awkward and should be revised.

Comments on the Quality of English Language

In the acknowledgments section, the author mentioned using Chat GPT for translation assistance. Some of the sentence structures are a bit awkward and should be revised.

Author Response

Comments and Suggestions for Authors

This paper reports a case where Tannerella forsythia, a periodontal pathogen, was detected for the first time in the synovial fluid of patients with osteoarthritis (OA), which is of certain innovation and clinical significance. Only by using PCR to detect DNA, it is impossible to distinguish between live bacteria and dead bacteria.

RESPONSE: We thank the Reviewer for this valuable comment and recognition of the clinical relevance of our work. We agree with this remark and have therefore mentioned in the abstract (The finding should be interpreted with caution, as detection of bacterial DNA does not indicate viability or causative involvement), discussion (However, it should be interpreted as hypothesis-generating rather than evidence of causality, as the presence of bacterial DNA does not confirm microbial viability or a pathogenic role in joint disease) and conclusion (It should be noted that detection of bacterial DNA does not confirm microbial viability or causative involvement).

 

2. In the acknowledgments section, the author mentioned using Chat GPT for translation assistance. Some of the sentence structures are a bit awkward and should be revised.

RESPONSE: We thank the Reviewer for pointing this out. As MDPI offers professional Language and Figure Editing, we have submitted our manuscript to this service.

 

Comments on the Quality of English Language

In the acknowledgments section, the author mentioned using Chat GPT for translation assistance. Some of the sentence structures are a bit awkward and should be revised

RESPONSE: We thank the Reviewer for pointing this out. As MDPI offers professional Language and Figure Editing, we have submitted our manuscript to this service.

 

Reviewer 2 Report

Comments and Suggestions for Authors

This case report presents an interesting and potentially novel observation regarding the detection of Tannerella forsythia DNA in synovial fluid from a patient with severe periodontitis and knee osteoarthritis.

1. This study is based on a single case and only bacterial DNA was detected, the conclusions regarding oral-joint translocation should remain cautious. Detection of bacterial DNA does not confirm bacterial viability or direct pathogenic involvement in osteoarthritis progression.
2. The Discussion section would benefit from additional consideration of the oral–gut axis and systemic microbial translocation pathways, which may help explain the potential mechanisms underlying oral-joint dissemination. In particular, periodontal dysbiosis, epithelial barrier disruption, chronic inflammation, and circulating microbial products may contribute to bacterial translocation and distant tissue colonization. Incorporating recent literature related to oral-systemic microbial interactions would provide broader biological context for the findings. Please cite the relevant studies (DOI: 10.3390/biology14050496 and DOI: 10.3390/biology14101393).

 

Author Response

Comments and Suggestions for Authors

This case report presents an interesting and potentially novel observation regarding the detection of Tannerella forsythia DNA in synovial fluid from a patient with severe periodontitis and knee osteoarthritis. This study is based on a single case and only bacterial DNA was detected, the conclusions regarding oral-joint translocation should remain cautious. Detection of bacterial DNA does not confirm bacterial viability or direct pathogenic involvement in osteoarthritis progression.

RESPONSE: We appreciate the Reviewer’s insightful comment and constructive evaluation. We agree with this remark and have therefore mentioned in the abstract (The finding should be interpreted with caution, as detection of bacterial DNA does not indicate viability or causative involvement), discussion (However, it should be interpreted as hypothesis-generating rather than evidence of causality, as the presence of bacterial DNA does not confirm microbial viability or a pathogenic role in joint disease) and conclusion (It should be noted that detection of bacterial DNA does not confirm microbial viability or causative involvement).

 

The Discussion section would benefit from additional consideration of the oral–gut axis and systemic microbial translocation pathways, which may help explain the potential mechanisms underlying oral-joint dissemination. In particular, periodontal dysbiosis, epithelial barrier disruption, chronic inflammation, and circulating microbial products may contribute to bacterial translocation and distant tissue colonization. Incorporating recent literature related to oral-systemic microbial interactions would provide broader biological context for the findings. Please cite the relevant studies (DOI: 10.3390/biology14050496 and DOI: 10.3390/biology14101393).

RESPONSE: We are grateful for this valuable suggestion that strengthens the biological context of the manuscript. We agree with this remark and have therefore added additional consideration of the oral–gut axis and systemic microbial translocation pathways, which may help explain the potential mechanisms underlying oral-joint dissemination. Also, the suggested studies are now included in the discussion (This systemic perspective is further supported by recent studies, where periodontal inflammation was shown to alter oral microbial composition and inflammatory signaling pathways [20]. In parallel, disruption of intestinal barrier integrity and gut microbial homeostasis associated with periodontal inflammation has also been described supporting the concept of an oral-gut inflammatory axis involved in systemic inflammatory response [21]).

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors, congratulations on your work; it is very interesting, but I would like to offer some suggestions to improve the manuscript and make it worthy of publication.
In the introduction, osteoarthritis needs to be better defined; it is necessary to determine the epidemiology, which patients are affected by this condition, whether they are adult or pediatric patients, for example, and how many cases occur annually worldwide.  
In addition, the difference between gram-negative and gram-positive bacteria needs to be explained.  
Line 62: what is defined as lumbosacral syndrome?  
Did the patient benefit from the therapy? Explain it better because this part is missing.  
In the discussion, you need to add articles that have addressed a similar topic and make a comparison with your article.  
The future perspectives and study limitations are missing.  
Additionally, in the discussion, you need to explain the bacteria you studied better, defining and describing their characteristics and their morbidity.  

Author Response

Comments and Suggestions for Authors

Dear authors, congratulations on your work; it is very interesting, but I would like to offer some suggestions to improve the manuscript and make it worthy of publication.

In the introduction, osteoarthritis needs to be better defined; it is necessary to determine the epidemiology, which patients are affected by this condition, whether they are adult or pediatric patients, for example, and how many cases occur annually worldwide. 

RESPONSE: We thank the Reviewer for the positive evaluation of our work and for the valuable suggestions provided for enhancing the manuscript. We appreciate the Reviewer’s important suggestion regarding the introduction section. We agree with this remark and have therefore added additional consideration regarding osteoarthritis in the introduction (Osteoarthritis is the most common musculoskeletal disorder among middle-aged and elderly populations. It is primarily characterized by the destruction of articular cartilage; however, the pathological process affects all joint tissues. As early as 2019, the global number of people with osteoarthritis exceeded 500 million, making OA one of the leading causes of chronic pain and long-term disability in older adults. The incidence and global burden of osteoarthritis continue to increase, driven primarily by population aging and the rising prevalence of obesity).

 

In addition, the difference between gram-negative and gram-positive bacteria needs to be explained. 

RESPONSE: We thank the Reviewer for this helpful suggestion and acknowledge its importance. We have therefore explained the difference between Gram-negative and Gram-positive bacteria in the discussion (Importantly, all periodontal pathogens investigated in this study were Gram-negative bacteria. Unlike Gram-positive bacteria, Gram-negative bacteria possess an outer membrane containing lipopolysaccharides (LPS), potent stimulators of host inflammatory responses and produce virulence factors such as proteolytic enzymes and leukotoxins).

 

Line 62: what is defined as lumbosacral syndrome? 

RESPONSE: We thank the Reviewer for this clarification request. We have further explained and defined the lumbosacral syndrome in the case presentation (The patient had a history of degenerative disease of the lumbosacral spine and an L5-S1 disc herniation, for which she was taking Arcoxia 60 mg and Lyrica 75/150 mg).

 

Did the patient benefit from the therapy? Explain it better because this part is missing. 

RESPONSE: We appreciate this important comment regarding clinical outcomes. We have therefore explained the details regarding patient`s benefit from the therapy in the follow-up and outcomes (Following therapy, a partial periodontal improvement was observed, primarily reflected by reduced periodontal inflammation. The patient also reported subjective improvement in joint-related symptoms. At follow-up, no clinical signs of periodontal or joint complications were observed, indicating a stable clinical outcome).

 

In the discussion, you need to add articles that have addressed a similar topic and make a comparison with your article. 

RESPONSE: We are grateful for this valuable suggestion aimed at strengthening the Discussion. We have therefore added articles that have addressed a similar topic and made a comparison with our manuscript (Comparable associations between periodontal pathogens and synovial inflammation have also been described in inflammatory arthritides, particularly rheumatoid arthritis, further supporting the concept of oral–joint microbial interactions [9,10]. These observations suggest the possibility of hematogenous dissemination of oral pathogens from periodontal tissues to the synovial space. Similar to previous studies reporting oral bacterial DNA in synovial samples, this case supports the hypothesis of microbial translocation from the oral cavity to the joint environment. In contrast to these reports, this study identifies Tannerella forsythia in synovial fluid, thereby expanding the spectrum of oral microorganisms potentially associated with OA-related inflammatory processes).

 

The future perspectives and study limitations are missing. 

RESPONSE: We thank the Reviewer for this important observation and acknowledge it. We have added the additional future perspectives in the discussion (Future studies should include larger patient cohorts and apply quantitative and genomic approaches, such as quantitative PCR (qPCR) and metagenomic sequencing, in order to better elucidate the potential role of oral pathogens in osteoarthritis and to further clarify the mechanisms underlying microbial translocation and its contribution to low-grade systemic inflammation and joint degeneration) and emphasized study limitations (This study has several limitations that should be acknowledged. First, the observation is based on a single case, which limits the ability to draw causal inferences regarding the relationship between microbial factors and joint degenerative processes. Second, quantitative PCR data were not available and bacterial load was assessed only semi-quantitatively. Third, functional studies assessing bacterial activity in the synovial environment were not performed; thus, the presence of bacterial DNA does not confirm the presence of viable microorganisms or their active involvement in inflammation).

 

Additionally, in the discussion, you need to explain the bacteria you studied better, defining and describing their characteristics and their morbidity.

RESPONSE: We thank the Reviewer for this insightful recommendation. We have added the sentences regarding other periodontal pathogens in the discussion (In addition to their individual virulence factors, the periodontal pathogens investigated in this study exhibit synergistic interactions within the subgingival biofilm that promote chronic inflammation and tissue destruction. Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola form the so-called “red complex,” strongly associated with advanced periodontal disease, while Aggregatibacter actinomycetemcomitans is also recognized as an important periodontal pathogen associated with aggressive forms of periodontitis and enhanced inflammatory response. Prevotella intermedia contributes to biofilm maturation, dysbiosis, and inflammatory activation within periodontal tissues).

 

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors, you followed my advice and have greatly improved the manuscript; congratulations.
I won’t be asking for any further changes.