All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
Thanks for addressing the remaining comments!
[# PeerJ Staff Note - this decision was reviewed and approved by Konstantinos Kormas, a PeerJ Section Editor covering this Section #]
As below
As below
As below
All issues have been addressed.
Please address the few remaining comments, thanks!
Title & Abstract
Title:
The title of the manuscript is clear, detailed and capture the content and focus of the manuscript which is to evaluate the “clinical significance of gut microbiota of chronic obstructive pulmonary disease with functional abdominal bloating and distension”
Abstract:
The abstract of the study is structured. The Abstract adequately capture the content and focus of the manuscript. The authors provided adequate background information on the growing interests on the relationship between fecal microbiota in COPD patients with functional abdominal bloating/distension (FABD) to identify precision medicine biomarkers. Also, the study has very clear study objective which is “to establish an evaluation system for identifying specific biomarkers that connect COPD-associated FABD with microbial dysregulation”
The Methods section is detailed, succinct and well-written. The authors provided a detailed description of the data sources and participants (consisting of COPD&FABD, COPD, and healthy controls) were provided. Also, next-generation sequencing (NGS) of their fecal samples was done, gut microbiota diversity/composition and immune parameters (serum IgG, CD4+/CD8+ T cells) were identified and compared.
The Results are detailed and fairly well-written capturing the key objectives of the study including distinct fecal microbiota for each group.
Also, the Conclusion section are detailed summarizing key findings and its implications for clinical care including that gut microbiota signatures, may serve as non-invasive biomarkers for COPD progression and FABD diagnosis, warranting clinical validation.
In the revised manuscript, the authors have strengthened the Abstract section as recommended in the previous review of the manuscript. Also, the authors have made necessary corrections in the Results section of the Abstract section by stating the actual p-values obtained as recommended.
Introduction
The authors provided a detailed review of the literature highlighting the pathophysiology of COPD including irreversible airflow limitation, chronic pulmonary inflammation, and small airway remodeling. Also, the authors highlighted that COPD is currently the fourth leading cause of death worldwide causing approximately 3.2 million deaths annually. Currently, studies have revealed a variation in respiratory microbial diversity of COPD patients according to various stages of the disease. However, limited studies have explored the relationship between gut microbiota and COPD despite the existence. Therefore, the authors did partly justify the need for the present study as there are limited studies that showed relationship between gut microbiota and COPD, and the study has well-written study objectives which is: “to establish an evaluation system for identifying specific biomarkers that connect COPD-associated FABD with microbial dysregulation”.
The authors have made necessary corrections in the Introduction section of the manuscript as recommended. Overall, the authors have satisfactorily addressed all the issues raised in this section of the manuscript.
Figures & Tables
All the Tables and Figures are complete, self-explanatory and cited in the text
Material and Methods
The Materials and Methods section is fairly well-written. The authors provided a clear description of the study. Also, details of the ethical approval of the study and other approvals were stated. There was a clear description of the study participants including inclusion and exclusion and data sources. COPD definition and definition of FABD. Furthermore, the authors provided adequate description of variables extracted from the database as well as definitions, study outcomes. Also, there is fair description of the study design and study period in the revised manuscript. Therefore, the Methods described are fairly repeatable and adequate level of detail has been provided to enable replication of the analysis. Also, details of the statistical methods were fairly well-written. The authors have made necessary corrections in the Methods section of the manuscript in particular; the authors have clearly stated the study design (e.g. descriptive or observational study) and the study period as recommended. Overall, the authors have satisfactorily addressed all the issues raised in this section of the manuscript.
Results
The paper makes a meaningful contribution to the advancement of the field by describing the relationship between gut microbiota and COPD. Overall, the authors reported the Demographic Characteristics of the COPD Population. Also, the authors adequately described the Comparison of Clinical Data among COPD, COPD&FABD, and HC Groups which revealed no significant differences in most laboratory and immunological indicators. Also, the authors described the Composition of the intestinal microbiota in the COPD, COPD&FABD, and HC groups highlighting that the COPD and COPD&FABD groups have similar microbial phyla abundance. The authors described the species alpha diversity and beta diversity analysis and difference analysis. Also, the authors reported the performance evaluation of key microbial biomarkers and diagnostic models as well as the random Forest analysis. The findings presented appears plausible and reasonable. All the Tables and Figures are complete, self-explanatory and cited in the text.
In the revised manuscript, the authors have made necessary corrections in the Results section of the manuscript by stating the actual p-values obtained as recommended. Overall, the authors have satisfactorily addressed all the other issues raised during the previous review of this section of the manuscript.
Discussion
The Discussion is well written as important studies in this area were reviewed and cited in the field by describing the relationship between gut microbiota and COPD. The authors did adequately discuss what is known in the literature and adequately compared their findings with other studies that have demonstrated the impact of gut flora had been suggested to be associated with the progression of a variety of lung diseases including COPD. Also, the authors discussed their findings highlighting that Enterococcus faecium enrichment occurred in (COPD, and in COPD&FABD), which was absent in health controls. Furthermore, the authors highlighted and discussed their observation of distinct microbiome dysbiosis along the oral-airway-gut axis in COPD patients compared to HC, with ecological perturbations exhibiting stage-dependent progression and severity-associated taxonomic shifts. Also, the authors discussed the immune-microbiota interactions linked to species diversity analysis and difference analysis. In addition, the authors did provide a well-written paragraph highlighting the limitations of the study.
Conclusion
The Conclusion paragraph is fairly well-written does align with the key findings obtained in the study that distinct gut microbiota signatures occur in COPD patients with FABD, particularly Enterococcus faecium enrichment and fungal biomarkers. In addition, the authors did provide clear implications from their findings to improve clinical practice especially as finding highlights the potential for the development of non- invasive diagnostics and microbiota-modulating therapies to improve symptom management and prognosis of COPD in underserved patient population.
Overall, the investigators have addressed my issues and clarified the work to an acceptable degree. There are some typos and also COPD+FABD and COPD&FABD are used interchangeably throughout the manuscript and it should be addressed before final acceptance. Otherwise, I commend the authors for their clarity and addressing the strengths and weaknesses of their manuscript.
as above
as above
as above
Please address all reviewers' comments.
**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
Title:
The title of the manuscript is clear, detailed and capture the content and focus of the manuscript which is to evaluate the “clinical significance of gut microbiota of chronic obstructive pulmonary disease with functional abdominal bloating and distension”
Abstract:
The abstract of the study is structured. The Abstract adequately capture the content and focus of the manuscript. The authors provided adequate background information on the growing interests on the relationship between fecal microbiota in COPD patients with functional abdominal bloating/distension (FABD) to identify precision medicine biomarkers. Also, the study has very clear study objective which is “to establish an evaluation system for identifying specific biomarkers that connect COPD-associated FABD with microbial dysregulation”
The Methods section is detailed, succinct and well-written. The authors provided a detailed description of the data sources and participants (consisting of COPD&FABD, COPD, and healthy controls) were provided. Also, next-generation sequencing (NGS) of their fecal samples was done, gut microbiota diversity/composition and immune parameters (serum IgG, CD4+/CD8+ T cells) were identified and compared, however, and the section did not indicate the study design and setting.
The Results are detailed and fairly well-written capturing the key objectives of the study including distinct fecal microbiota for each group.
Also, the Conclusion section are detailed summarizing key findings and its implications for clinical care including that gut microbiota signatures, may serve as non-invasive biomarkers for COPD progression and FABD diagnosis, warranting clinical validation.
Recommended revisions
i) Page 7, line 22-25: The authors need to clearly state the study design and setting in the Methods section of the paper
ii) Page 7, line 25-28: In the Results section, the authors need to state the actual p-values obtained rather than p <0.05 or p<0.001 or p>0,05.
Introduction
The authors provided a detailed review of the literature highlighting the pathophysiology of COPD including irreversible airflow limitation, chronic pulmonary inflammation, and small airway remodeling. Also, the authors highlighted that COPD is currently the fourth leading cause of death worldwide causing approximately 3.2 million deaths annually. Currently, studies have revealed a variation in respiratory microbial diversity of COPD patients according to various stages of the disease. However, limited studies have explored the relationship between gut microbiota and COPD despite the existence. Therefore, the authors did partly justify the need for the present study as there are limited studies that showed relationship between gut microbiota and COPD, and the study has well-written study objectives which is: “to establish an evaluation system for identifying specific biomarkers that connect COPD-associated FABD with microbial dysregulation”.
Recommended revisions
i) There is a need to mention and discuss the common risk factors for COPD and its relation with the gut -lung axis
ii) Line 91 to 93: “Concurrently, the gut microbiomes utility in non-invasive diagnosis has been validated in colorectal cancer, hepatocellular carcinoma, and alcoholic liver disease (Yu et al., 2017; Ren et al., 2019; Smirnova et al., 2020), underscoring its translational potential across diseases.”
Comment: While this information is important, I feel this would better-off in the Discussion section in situating the gut microbiome’s utility in non-invasive diagnosis of various diseases including COPD
iii) I find the review of the literature on studies on the relationship between gut microbiota and COPD to be very poor. There is a need for the authors to discuss how the gut microbiota influences COPD including its role in inflammation and immunity, gut permeability and translation and host factors like smoking. In addition, there is a need for the authors to highlight the bidirectional influence of COPD on the gut microbiota; and its implications for COPD treatment and prevention including clarifying diagnostic biomarkers, therapeutic targets and protective microbes. Please see:
• https://doi.org/10.1016/j.biopha.2023.115150
• https://doi.org/10.1016/j.heliyon.2024.e30612
**PeerJ Staff Note:** It is PeerJ policy that additional references suggested during the peer-review process should only be included if the authors are in agreement that they are relevant and useful.
Figures & Tables
All the Tables and Figures are complete, self-explanatory and cited in the text
Recommended revisions
i) “Table 1 Patients. Baseline information”
Comment: In the statistical comparison, please, use symbols to indicate the p values from Chi-square test and those from Z test. Also add a footnote on the Table describing all abbreviations on the Table.
Material and Methods
The Materials and Methods section is fairly well-written. The authors provided a clear description of the study. Also, details of the ethical approval of the study and other approvals were stated. There was a clear description of the study participants including inclusion and exclusion and data sources. COPD definition and definition of FABD. Furthermore, the authors provided adequate description of variables extracted from the database as well as definitions, study outcomes. However, there is poor description of the study design and study period.
Therefore, the Methods described are fairly repeatable and adequate level of detail has been provided to enable replication of the analysis. Also, details of the statistical methods were fairly well-written.
Recommended revisions
i) Line 141: Study design
Comment: The subheading “Study design” should be moved to line 110.
Under this section, the authors need to state the study design (e.g. descriptive or observational study) and the study period (carried out from……..).
ii) Line 141: Study design
Comment: The subheading “Study design” should be changed to “Measurements and data collection” in line 110.
iii) Line 115-116: “To avoid the impact of diet on the gut microbiota, each subject was required to maintain a stable diet within two weeks.”
Comment: The authors need to define what they meant by “stable diet”.
Iv) The authors need to clearly state how they arrived at the sample size to be used by the study in order to highlight whether the study had sufficient power to detect differences between the groups.
Results
The paper makes a meaningful contribution to the advancement of the field by describing the relationship between gut microbiota and COPD. Overall, the authors reported the Demographic Characteristics of the COPD Population. Also, the authors adequately described the Comparison of Clinical Data among COPD, COPD&FABD, and HC Groups which revealed no significant differences in most laboratory and immunological indicators. Also, the authors described the Composition of the intestinal microbiota in the COPD, COPD&FABD, and HC groups highlighting that the COPD and COPD&FABD groups have similar microbial phyla abundance. The authors described the species alpha diversity and beta diversity analysis and difference analysis. Also, the authors reported the performance Evaluation of key microbial biomarkers and diagnostic models as well as the random Forest analysis. The findings presented appears plausible and reasonable. All the Tables and Figures are complete, self-explanatory and cited in the text. Although, some of the Tables require additional clarifications.
Recommended revisions
i) In the Results section, the authors need to state the actual p-values obtained rather than p <0.05 or p<0.001 or p>0,05.
Discussion
The Discussion is well written as important studies in this area were reviewed and cited in the field by describing the relationship between gut microbiota and COPD. The authors did adequately discuss what is known in the literature and adequately compared their findings with other studies that have demonstrated the impact of gut flora had been suggested to be associated with the progression of a variety of lung diseases including COPD. Also, the authors discussed their findings highlighting that Enterococcus faecium enrichment occurred in (COPD, and in COPD&FABD), which was absent in health controls. Furthermore, the authors highlighted and discussed their observation of distinct microbiome dysbiosis along the oral-airway-gut axis in COPD patients compared to HC, with ecological perturbations exhibiting stage-dependent progression and severity-associated taxonomic shifts. Also, the authors discussed the immune-microbiota interactions linked to species diversity analysis and difference analysis. In addition, the authors did provide a well-written paragraph highlighting the limitations of the study.
Conclusion
The Conclusion paragraph is fairly well-written does align with the key findings obtained in the study that distinct gut microbiota signatures occur in COPD patients with FABD, particularly Enterococcus faecium enrichment and fungal biomarkers. In addition, the authors did provide clear implications from their findings to improve clinical practice especially as finding highlights the potential for the development of non- invasive diagnostics and microbiota-modulating therapies to improve symptom management and
Prognosis of COPD in underserved patient population.
None
I am reviewing the manuscript, "The clinical significance of gut microbiota of chronic obstructive pulmonary disease with functional abdominal bloating and distension submitted by Lu et al." Overall, their work is thorough and well described, but there is not a clear connection to COPD and COPD&FABD - this is probably the weakest part of their manuscript and needs to be better connected. Are symptoms also related to underlying GI disease or related to viral infections imparting some gastrointestinal effects? Moreover, it is also not clear if these phenotypes are associated with worsening clinical disease and I think that the authors should clarify a bit better.
1. Missing discussion on 16S? Whole genome? metatranscriptome sequencing? It's not clear how this was done and what exactly the authors did, please include this portion for review. Moreover, did the authors include any other control samples for review? If there are no other control samples I suggest that the authors include this was a weakness.
2. Most of COPD exacerbations are a result of viral infections, did the authors consider this in their analysis? If the sequencing did not include these viral infections, did the authors analyze the respiratory viral panels associated with the exacerbation events? There is thought that this can impact the gut microbiome.
3. Overall, very descriptive, it's difficult to ascertain the directionality. I think that there should be some discussion on how the authors should operationalize the findings - should gut microbiome be evaluated for gut symptoms or acute exacerbations? I think the authors should organize what is known about the gut microbiome in COPD and connect it to COPD&FABD to help the readers understand the importance of their work.
I'll be using the PDF page numbers and leftmost line numbers.
Abstract
Page 7, Line 22 "COPD&FABD" It would be good to at least define FABD first, what actually do the authors mean by functional? Does it impede pulmonary or gastrointestinal functions? The specificity could help us understand the interpretation here.
Page 7, Line 31 "Notably, Enterococcus faecium was highly abundant in patients (22.04–26.92%) but absent in HC." This is very interesting, but what's the interpretation? Even in the abstract, it would be helpful to address this presence of absence in disease.
page 7, Line 32 What exactly is the random forest model trying to do? Determine differences between COPD HC or COPD+abdominal issues? The description in the results need to be more clear.
Introduction
Page 7 Line 41 to Page 8, Line 43 These two lines are a bit repetitive, you could summarize and shorten the thoughts.
Page 8, Line 44 "COPD emerges as a major socioeconomic and public health challenge, disproportionately affecting healthcare infrastructures and resource allocation in low- and middle-income countries (LMICs) (Halpin et al., 2019)." I am not sure what this has to do with gut microbiome issues, could be removed for clarity or brevity of the introduction. I suggest that it be removed or contextualized for the study.
Page 8, Line 54 "However, most of the existing studies focus on respiratory microbiota, and the exploration of the relationship between gut microbiota and COPD is still insufficient." You could rephrase to say that clarification on the role of gut microbiome on COPD and COPD AE needs to be performed. Insufficient sounds like people are not doing enough study, there are a lot of gut-microbiome researchers, but perhaps the tone could be improved by saying that it requires further clarification.
Pag 9, Line 66 "FABD directly implicates gut dysbiosis as a potential pathophysiological link, offering a unique opportunity to explore microbiota-mediated mechanisms in COPD progression." I want to challenge this assertion, there is no citations associated with this assertion, so there as far as I know, have no gut-microbiome evidence of gut dysbiosis + FABD which is what the authors are saying. I think if there is an esoteric citation or implication from other studies that the authors should discuss functional abdominal issues associated with gut microbiomes here. The assertion in absence of evidence is not sufficient to prove their point.
Page 9, Line 81 to page 10, Line 93 - there is a mix of diagnostic studies and studies related to describing the gut microbiome. The authors should consider splitting and organizing the section a bit better. for example, the diagnostic studies could be removed. moreover, the authors also should point out that directionality for these studies have not been established.
Page 10,Line 96-97 "Given the high prevalence of FABD and its proposed link to gut dysbiosis, distinct from immune-dominated pathways in other COPD comorbidities. This study aims to characterize fecal microbiota signatures in COPD&FABD via NGS, establishing microbial biomarkers for non-invasive diagnosis." I don't think that it's been establish that the immune pathways are all that different than your typical COPD ones? I would carefully reiterate this sentence.
Page 10, Line 104 - the paragraph needs a better hypothesis to understand what the authors are exploring. Moreover, as far as I know a ot of directionality is established in COPD and gut-lung microbiome. For example, we do not know if COPD alteres the gut microbiome or the gut microbiome alters the outcomes in COPD. Unfortunately, this would leave the authors in a very descriptive manuscript unless they can establish causality.
Materials and Methods
Page 11, Line 115 - "BMI 18.5 ..." The study seemed to recruit some thin to normal BMI patients. With the underweight patients, how many were there? What was the median weight. When the authors discuss a stable diet, what exactly does that mean?
Page 11, Line 125 "(1) Chronic cough or sputum production, dyspnea, a history of recurrent lower respiratory tract infections; (2) Exposure history to COPD risk factors; (3) Post-bronchodilator 127 lung function test showing FEV1/FVC < 70%." The criteria seem very specific for the CMA - however, as far as I know that ATS guidelines do not include recurrent LRTI - this is unique for the CMA criteria. Along with recurrent infections, does that mean viral? bacterial? Did the authors take into account antibiotic usage prior to admission? These would be important to know. This also is concerning for the following comment:
Page 12, Line 139 "6. Has used drugs affecting the intestinal flora in the past 6 months (including antibiotics and probiotics); 7" If the CMA critera includes recurrent lower respiratory tract infections, doesn't that imply that a lot of these patients had been exposed to antibiotics as well? Also, there have been viral infections which can also affect gut microbiota - it would be interesting to see whom falls into which group with increased viral infections. Moreover, while antibiotics before 2 weeks, there is some evidence that antibiotics exposure may have up to8 weeks of affects on the lung microbiome - did the authors provide this data?
Page 13, Line 150 "Meanwhile, serum immunoglobulin IgG and CD4+ T-cell and CD8+ T-cell levels were detected to evaluate the correlation between the intestinal flora and the immune function o the organism." I think the 'organism' is the patient or participant. The use of organism probably should be reserved to mice.
Page 13, Line 154 to Line 168, the authors should include all of the statistical programs, tools, versions that were used - with the appropriate citations for the works that support their analysis. Listing the equation or methods is not enough for methods when discussion gut microbiome. This will also include code used to generate their conclusions, which should be hosted or uploaded for review.
Results
Page 14, Line 171 The comparison for table 1 (line 174) is missing the health group comparisons. It's strange since the authors use all three groups for comparis, but it's missing from the Table 1 (page 35). There's also some issus which the authors should address especially units for comparisons (e.g., procalcitonin). Also, what are the immunoglobulin counts. Also how exactly the CD4+ and CD8+ cells measured, is it flow? is it IHC? Probably should be more specific about these comparisons.
Page 14, Line 181 "Enterococcus faecium and Bifidobacterium longum are more abundant, with the COPD group at 22.04% and 13.24%, and the COPD&FABD group at 26.92% and 6.48%, compared to the HC group at 0% and 1.71% (Figure 2B)." The authors should consider pulling out the individual relative abundance and read counts to do a straight comparison. It is difficult to see the summation of these figures 2B - the individual comparisons would be interesting to see.
Page 15, Line 188 "The Chao1 and ACE indices showed that the COPD&FABD group had significantly higher richness than healthy individuals (P<0.05)." The finding is a little odd, since you would expect that to be lower - unless of course there are unknown mediators or confounders here.
Page 15, Line 192 "PCA and PCoA analyses revealed significant differences in fecal microbiota composition among the three groups (R2<0.2, P<0.05), with higher similarity between the COPD and COPD&FABD groups (P>0.05) and significant ³-diversity differences compared to HC group (P<0.01) (Figure 3B)." I feel overall, this would be a overall negative difference in compositional differences if you're interpreting this. I suggest some exposition here would be all right, given the context. Without explaining much, the assumption would be that there's no new differences here.
Page 15, Line 197-203 "The relative abundance ..." You know, I really like tools such as Dirichlet Multinomial Modeling in order to find differences among groups too. The LEFSE tool tends to use presumed groups HC, COPD, and COPD&FABD thus it would be interesting to see if there are other groups there. I do not have an issue with the 3-way LEFSE comparisons, but I recommend that the authors do a 1x1 comoparison across groups both with LEFSE and another tool such as EdgeR or DESEq2.
Page 15, Line 205 to Page 210 "random forest ..." This section is unclear - what exactly is the diagnostic outcome of tinerest? I recommend that this section should be written a bit more clearly - the AUC is supposed to diagnose COPD+FABD? I think that this is not clear from this portion and should be re-written.
Discussion:
Page 16, Line 220, "Building on this foundation, the present study, with the aid of NGS testing for fecal pathogenesis, further revealed significant differences in the composition of fecal microflora between patients with COPD combined with FABD and healthy populations." The discussion is a bit anemic, should be more specific for COPD vs. COPD+FABD - what are the implications of these differences? The first portion Line 212 to 220 could be shortened a bit, please let me know what is different or what the study learned from examining the fecal microbiome.
Page 17, Line 231 "In the present study, the analysis of species composition revealed that in both the COPD group and the COPD&FABD group, the top ten genera in relative abundance included Enterococcus faecalis, Bifidobacterium longum, and Clostridium baumannii, which play important roles in the gut microbial community." This section here is suggesting that COPD and COPD+FADB hasa lot of overlaop - this needs to be clarified in the context of perhaps FABD? There are significant overlaps between these two groups.
Page 17, Line 240 "For instance, Enterococcus faecium is a known gas-producing genus, and its overrepresentation could directly explain the abdominal distension symptoms in FABD patients (Wei, Palacios & Plamer, 2024). This suggests that while COPD itself drives broad gut dysbiosis, FABD comorbidity may further select for taxa exacerbating local gas accumulation or visceral hypersensitivity, offering a potential target for symptom-specific interventions." I do not necessarily think that this is the correct conclusion and is an overstatement. The manuscript does not actually mechanistically test that COPD drives broad gut dysbiosis as the authors suggest. In fact, the opposite can be true which gut dysbiosis may drive COPD. I think that there has to be careful description and careful attribution to cause and effect in microbiome data. As far as I know, no mechanism has necessarily been described by the authors in their work, so directionality or causality has not been established thus this conclusion cannot be the only one that the authors should be discussing here.
Page 18, Line 252, "Notably, this elevation in ³-diversity contrasts with studies reporting
reduced diversity in advanced COPD (GOLD III-IV) (Drossman, 2016), suggesting that FABD
comorbidity may introduce unique microbial signatures in early-to-moderate COPD" I wonder why they found these differences and I think the authors should discuss this a bit more.
Page 19, Line 273, "These findings align with emerging evidence that gut dysbiosis contributes to both respiratory and astrointestinal pathologies (Ren et al., 2019; Zheng et al., 2020; Coker et al., 2022) yet uniquely highlight FABD as a comorbidity driven by microbial functional shifts rather than taxonomic overlap with COPD alone." How about the effects of inhaled corticosteroids? What specific gut and lung pathologies are the authors discussing here, I recommend to be a bit more specific.
Minor
Page 6, Line 19 "Chronic obstructive pulmonary disease (COPD) is a high morbidity/mortality disease." I think it would be ok to say high morbidity and mortality disease. The slash implies one or the other. I think you can do away and use an "and" between high morbidity and mortality.
Page 10, Line 96-99 "Given the high prevalence of FABD and its proposed link to gut dysbiosis, distinct from immune-dominated pathways in other COPD comorbidities. This study aims to characterize fecal microbiota signatures in COPD&FABD via NGS, establishing microbial biomarkers for non- invasive diagnosis." this could be one sentence.
Please see previous section
Please see previous section
Please see previous section
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.