The Effect of Gut Microbiome, Neurotransmitters, and Digital Insights in Autism
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsDear authors,
Thank you for the interesting review, but in my opinion the aim of the study was not achieved, as the paper lacks any information on the quantitative and qualitative composition of the gut microbiome. It is necessary to revise some sections of the review and make some edits:
1. Lines 19-21 - The current study aims to investigate the interaction between the quantitative and qualitative composition of the gut flora and neurotransmission in humans, as well as their influences on the appearance and progression of the symptoms of Autism Spectrum Disorder. – In my opinion, it is not correct to write that the purpose of the review is only to study. It would probably be more correct to define the purpose as follows ‘’Research and systematic of data about the interaction between the quantitative and qualitative composition of the gut flora and neurotransmission in humans, as well as their influences on the appearance and progression of the symptoms of Autism Spectrum Disorder.’’
2. The purpose of the review should be stated in the Introduction section.
3. Line 51 -GABA - requires transcription at first mention in the text.
4. Line 103 – “2. Materials and Methods” – In my opinion it is not correct to use this title for the review section. Please revise the title of the article according to the rules of the journal.
5. Line 106 - ICT - requires transcription at first mention in the text.
6. Line 135 - CNS - requires transcription at first mention in the text.
7. Lines 231-232 -‘GABA is considered the foremost inhibitory neurotransmitter of the central nervous system’. – The following text does not explain this statement. What is the cause of inhibition? And what is its function in the human body? Lines 231-238 - in my opinion should be reworded. And it should be clarified that GABA is an inhibitory neurotransmitter in the mature brain, whereas it plays a depolarising and excitatory role in the developing brain.
(for example, Wu, C., Sun, D. GABA receptors in brain development, function, and injury. Metab Brain Dis 30, 367–379 (2015). https://doi.org/10.1007/s11011-014-9560-1;
Cellot G and Cherubini E (2013) Functional role of ambient GABA in refining neuronal circuits early in postnatal development. Front. Neural Circuits 7:136. doi: 10.3389/fncir.2013.00136).
8. In section ‘3.2 Neurotransmitters’ - it would be nice to mention the role of excitation/inhibition balance in RAS (for example, Bernardino I, Dionísio A, Violante IR, Monteiro R and Castelo-Branco M (2022) Motor Cortex Excitation/Inhibition Imbalance in Young Adults With Autism Spectrum Disorder: A MRS-TMS Approach. Front. Psychiatry 13:860448. doi: 10.3389/fpsyt.2022.860448)
9. Line 292 - 4. Results - it is necessary to rename the section according to the journal rules.
10. 10. Section ‘4.1 Gut microflora and its connection to NTs in ASD’ - the section lacks any information on the composition of the gut microbiome in people with autism (for example,Taniya MA, Chung HJ, Al Mamun A, Alam S, Aziz MA, Emon NU, Islam MM, Hong SS, Podder BR, Ara Mimi A, Aktar Suchi S, Xiao J. Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation. Front Cell Infect Microbiol. 2022 Jul 22;12:915701. doi: 10.3389/fcimb.2022.915701. PMID: 35937689; PMCID: PMC9355470.)“ Given the aims of the review and its title, this information is key. The review should include information comparing the composition of the gut microbiome of healthy people with that of people with ASD. Are there any signalling taxa present in the composition that may be associated with the development of RAS? How can this be used in therapeutic strategies for these disorders?
(for example р, Li N, Chen H, Cheng Y, Xu F, Ruan G, Ying S, Tang W, Chen L, Chen M, Lv L, Ping Y, Chen D, Wei Y. Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study. Front Cell Infect Microbiol. 2021 Oct 19;11:759435. doi: 10.3389/fcimb.2021.759435. Erratum in: Front Cell Infect Microbiol. 2021 Nov 23;11:801376. doi: 10.3389/fcimb.2021.801376. PMID: 34737978; PMCID: PMC8560686.).
11. Section ‘4.3 The Contribution of Digital Technology’ - very vague information, no specifics, a lot of general words.
12. Line 756 - 5. Discussion - need to rename the section.
13. Section 5: Discussion - contains repetition of information described above. This is acceptable in articles if the discussion mentions results, but it is redundant in a review.
14. It is also recommended that the structure of the review be revised.
Comments on the Quality of English LanguageThe English could be improved
Author Response
Dear Reviewer,
We would like to thank you for the constructive feedback and effort you put to our manuscript.
Comment 1 Lines 19-21 - The current study aims to investigate the interaction between the quantitative and qualitative composition of the gut flora and neurotransmission in humans, as well as their influences on the appearance and progression of the symptoms of Autism Spectrum Disorder. – In my opinion, it is not correct to write that the purpose of the review is only to study. It would probably be more correct to define the purpose as follows ‘’Research and systematic of data about the interaction between the quantitative and qualitative composition of the gut flora and neurotransmission in humans, as well as their influences on the appearance and progression of the symptoms of Autism Spectrum Disorder.’’
AUTHORS: We made the necessary modifications to lines 19-21
Comment 2 The purpose of the review should be stated in the Introduction section.
AUTHORS: We changed lines 98–101 as needed.
Comment 3 Line 51 -GABA - requires transcription at first mention in the text.
AUTHORS: Transcription was made at lines 66-67
Comment 4 Line 103 – “2. Materials and Methods” – In my opinion it is not correct to use this title for the review section. Please revise the title of the article according to the rules of the journal.
AUTHORS: As per the journal's guidelines the "Materials and Methods" section has been excluded from the review, so we have removed it.
Comment 5 Line 106 - ICT - requires transcription at first mention in the text.
AUTHORS: Transcription was made at line 101.
Comment 6 Line 135 - CNS - requires transcription at first mention in the text.
AUTHORS: Transcription was made at line 227.
Comment 7 Lines 231-232 -‘GABA is considered the foremost inhibitory neurotransmitter of the central nervous system’. – The following text does not explain this statement. What is the cause of inhibition? And what is its function in the human body? Lines 231-238 - in my opinion should be reworded. And it should be clarified that GABA is an inhibitory neurotransmitter in the mature brain, whereas it plays a depolarising and excitatory role in the developing brain.(for example, Wu, C., Sun, D. GABA receptors in brain development, function, and injury. Metab Brain Dis 30, 367–379 (2015). https://doi.org/10.1007/s11011-014-9560-1; Cellot G and Cherubini E (2013) Functional role of ambient GABA in refining neuronal circuits early in postnatal development. Front. Neural Circuits 7:136. doi: 10.3389/fncir.2013.00136).
AUTHORS: We have added additional information regarding your comments on lines 770-773.
Comment 8 In section ‘3.2 Neurotransmitters’ - it would be nice to mention the role of excitation/inhibition balance in RAS (for example, Bernardino I, Dionísio A, Violante IR, Monteiro R and Castelo-Branco M (2022) Motor Cortex Excitation/Inhibition Imbalance in Young Adults With Autism Spectrum Disorder: A MRS-TMS Approach. Front. Psychiatry 13:860448. doi: 10.3389/fpsyt.2022.860448)
AUTHORS: We included your suggestion in the line 770.
Comment 9 Line 292 - 4. Results - it is necessary to rename the section according to the journal rules.
AUTHORS: We renamed the section according to the journal's rules in lines 441, and 643.
Comment10. Section ‘4.1 Gut microflora and its connection to NTs in ASD’ - the section lacks any information on the composition of the gut microbiome in people with autism (for example,Taniya MA, Chung HJ, Al Mamun A, Alam S, Aziz MA, Emon NU, Islam MM, Hong SS, Podder BR, Ara Mimi A, Aktar Suchi S, Xiao J. Role of Gut Microbiome in Autism Spectrum Disorder and Its Therapeutic Regulation. Front Cell Infect Microbiol. 2022 Jul 22;12:915701. doi: 10.3389/fcimb.2022.915701. PMID: 35937689; PMCID: PMC9355470.)“ Given the aims of the review and its title, this information is key. The review should include information comparing the composition of the gut microbiome of healthy people with that of people with ASD. Are there any signalling taxa present in the composition that may be associated with the development of RAS? How can this be used in therapeutic strategies for these disorders?(for example Ñ€, Li N, Chen H, Cheng Y, Xu F, Ruan G, Ying S, Tang W, Chen L, Chen M, Lv L, Ping Y, Chen D, Wei Y. Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study. Front Cell Infect Microbiol. 2021 Oct 19;11:759435. doi: 10.3389/fcimb.2021.759435. Erratum in: Front Cell Infect Microbiol. 2021 Nov 23;11:801376. doi: 10.3389/fcimb.2021.801376. PMID: 34737978; PMCID: PMC8560686.).
AUTHORS: We have added additional information regarding your comments on lines 961-964 and 979-983.
Comment 11 Section ‘4.3 The Contribution of Digital Technology’ - very vague information, no specifics, a lot of general words.
AUTHORS: This section highlights how artificial intelligence contributes to digital health, specifically emphasizing the potential of digital tools for diagnosing and addressing ASD.
Comment 12 Line 756 - 5. Discussion - need to rename the section.
AUTHORS: We renamed the section in line 952.
Comment 13 Section 5: Discussion - contains repetition of information described above. This is acceptable in articles if the discussion mentions results, but it is redundant in a review.
AUTHORS: The section summarizes the main findings, enhancing the comprehension of the subject matter.
Comment 14 It is also recommended that the structure of the review be revised.
Comments on the Quality of English Language
The English could be improved
AUTHORS: The structure of the review was revised and some improvements were made in the use of language.
Reviewer 2 Report
Comments and Suggestions for AuthorsComments
The review manuscript titled “The Effect of Gut Microbiome, Neurotransmitters, and Digital Insights in Autism” by Bamicha et al highlights the recent developments in understanding the effects of gut microbiome on autism. Although, the manuscript has presented an interesting topic, there are some major concerns that deserve thorough attention before publication. The overall language of the manuscript is a kind of weak and has a scope for further improvements. Thus, authors are advised to improve the manuscript’s readability, merits as well as its understanding for the journal readers.
1. Line 17: his/her life...
2. Keywords: what is ICTs?
3. Line 84: what is ICTs? Mention your abbreviations in full on first use.
4. Lines 86-87 &114-115: Google scholar and ResearchGate are not yet recognized as authentic literature resources for peer-reviewed science, hence need to be removed. It also contradicts with your lines 111&112.
5. Lines 89-93: statements are very long and confusing. Revise for clarity.
6. Line 96: replace the term, “delves” with a better phrase. It is one of the terminologies that is frequently suggested by LLMs. Hence avoid it.
7. Lines 97-102: Revise, instead of discussing the review parts, authors should highlight the key scientific concepts that will highlight the novelty of the manuscript.
8. What was the criteria for restricting the search of the literature between 2005-2023 only?
9. Lines 114&115: Add the links and date of accession for PubMed, and Scopus databases.
10. Line 117: How was the categorization of retrieved literature performed?
11. Lines 121-123: Do bibliographic sources give unclear interpretations?
12. Lines 131-153: Making paragraphs of 2 or 3 sentences is very annoying. Authors should reorganize the manuscript inn a systematic order.
13. Lines 374: Authors should give a list of the microbes that are more prevalent in autism patients.
14. The potential mechanism by which gut microbiome effects the autism in humans is lacking in the manuscript. At least one figure describing the possible involvement of the gut microbes in autism is encouraged.
15. Since ether are no tables in the manuscript, authors can add a table highlighting the occurrence and relationship of different species of gut microbiota with neurotransmitters.
Comments on the Quality of English Language
Comments
The review manuscript titled “The Effect of Gut Microbiome, Neurotransmitters, and Digital Insights in Autism” by Bamicha et al highlights the recent developments in understanding the effects of gut microbiome on autism. Although, the manuscript has presented an interesting topic, there are some major concerns that deserve thorough attention before publication. The overall language of the manuscript is a kind of weak and has a scope for further improvements. Thus, authors are advised to improve the manuscript’s readability, merits as well as its understanding for the journal readers.
1. Line 17: his/her life...
2. Keywords: what is ICTs?
3. Line 84: what is ICTs? Mention your abbreviations in full on first use.
4. Lines 86-87 &114-115: Google scholar and ResearchGate are not yet recognized as authentic literature resources for peer-reviewed science, hence need to be removed. It also contradicts with your lines 111&112.
5. Lines 89-93: statements are very long and confusing. Revise for clarity.
6. Line 96: replace the term, “delves” with a better phrase. It is one of the terminologies that is frequently suggested by LLMs. Hence avoid it.
7. Lines 97-102: Revise, instead of discussing the review parts, authors should highlight the key scientific concepts that will highlight the novelty of the manuscript.
8. What was the criteria for restricting the search of the literature between 2005-2023 only?
9. Lines 114&115: Add the links and date of accession for PubMed, and Scopus databases.
10. Line 117: How was the categorization of retrieved literature performed?
11. Lines 121-123: Do bibliographic sources give unclear interpretations?
12. Lines 131-153: Making paragraphs of 2 or 3 sentences is very annoying. Authors should reorganize the manuscript inn a systematic order.
13. Lines 374: Authors should give a list of the microbes that are more prevalent in autism patients.
14. The potential mechanism by which gut microbiome effects the autism in humans is lacking in the manuscript. At least one figure describing the possible involvement of the gut microbes in autism is encouraged.
15. Since ether are no tables in the manuscript, authors can add a table highlighting the occurrence and relationship of different species of gut microbiota with neurotransmitters.
Author Response
Dear Reviewer,
We would like to thank you for the time and effort you put into improving our study while acknowledging the quality of it.
Comment 1 Line 17: his/her life...
AUTHORS: We changed lines 16-17 as needed.
Comment 2 Keywords: what is ICTs?
AUTHORS: Transcription was made at lines 33-34.
Comment 3 Line 84: what is ICTs? Mention your abbreviations in full on first use.
AUTHORS: Transcription was made at line 101.
Comment 4 Lines 86-87 &114-115: Google scholar and ResearchGate are not yet recognized as authentic literature resources for peer-reviewed science, hence need to be removed. It also contradicts with your lines 111&112.
AUTHORS: We made the modification we deemed necessary in line 104.
Comment 5 Lines 89-93: statements are very long and confusing. Revise for clarity.
AUTHORS: We also made the change required in lines 89-91.
Comment 6 Line 96: replace the term, “delves” with a better phrase. It is one of the terminologies that is frequently suggested by LLMs. Hence avoid it.
AUTHORS: We removed it.
Comment 7Lines 97-102: Revise, instead of discussing the review parts, authors should highlight the key scientific concepts that will highlight the novelty of the manuscript.
AUTHORS: We did it in lines 98-101.
Comment 8 What was the criteria for restricting the search of the literature between 2005-2023 only?
AUTHORS: As per the journal's guidelines, the "Materials and Methods" section has been excluded from the review, so we have removed it.
Comment 9 Lines 114&115: Add the links and date of accession for PubMed, and Scopus databases.
AUTHORS: The "Materials and Methods" section has been excluded from the review, so we have removed it.
Comment 10 Line 117: How was the categorization of retrieved literature performed?
AUTHORS: The "Materials and Methods" section has been eliminated because it was not included in the review, as per the journal's rules.
Comment 11 Lines 121-123: Do bibliographic sources give unclear interpretations?
AUTHORS: The "Materials and Methods" section has been eliminated because it was not included in the review, as per the journal's rules.
Comment 12 Lines 131-153: Making paragraphs of 2 or 3 sentences is very annoying. Authors should reorganize the manuscript in a systematic order.
AUTHORS: We changed lines 313-330 and 395- 399 as needed.
Comment 13 Lines 374: Authors should give a list of the microbes that are more prevalent in autism patients.
AUTHORS:
Comment 14 The potential mechanism by which gut microbiome effects the autism in humans is lacking in the manuscript. At least one figure describing the possible involvement of the gut microbes in autism is encouraged.
Comment 15 Since ether are no tables in the manuscript, authors can add a table highlighting the occurrence and relationship of different species of gut microbiota with neurotransmitters.
(13,14,15) AUTHORS: In a subsequent study, we will focus on the most important microbes, and metabolites associated with the microbiome of individuals with autism. Therefore, we will also include the corresponding tables.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe literature revealed the importance and influence of nutritional factors on neurotransmission performance and behavioral, social, and cognitive development among individuals with autism.
L23: For the manuscript is a review, so there is no need to write methods, for there is no test in the paper.
L51: “GABA” is the first time showed, please show the full name when the abbreviation was firstly used.
L103 For review was not different from article, authors should take care of this, instead using the frame for articles. The logic of the review should be modified.
L125-263 Review should not just put the previous research together. Such as part 3.1, 3.2,… should be put to the introduction. Also, the simple explanation for the concepts was no need. Please simplify.
L292 This part was the main contents for the paper. The part was not the result. Please rearrange the structure of the paper.
Author Response
Dear Reviewer,
Thank you so much for the time and effort you put into improving our study.
Comment 1 L23: For the manuscript is a review, so there is no need to write methods, for there is no test in the paper.
AUTHORS: The "Materials and Methods" section has been eliminated because it was not included in the review, as per the journal's rules.
Comment 2 L51: “GABA” is the first time showed, please show the full name when the abbreviation was firstly used.
AUTHORS: Transcription was made at lines 66-67.
Comment 3 L103 For review was not different from article, authors should take care of this, instead using the frame for articles. The logic of the review should be modified.
AUTHORS: The structure of the review was revised
Comment 4 L125-263 Review should not just put the previous research together. Such as part 3.1, 3.2,… should be put to the introduction. Also, the simple explanation for the concepts was no need. Please simplify.
AUTHORS: The necessary modifications were made in lines 229-447.
Comment 5 L292 This part was the main contents for the paper. The part was not the result. Please rearrange the structure of the paper.
AUTHORS: The structure of the review was revised
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsDear Authors,
Thank you for making changes to your publication. When I read the second version of your review, I had a small problem because the line numbering in the authors' response did not match the line numbering in the attached file, making it difficult to find the material mentioned in the response. It is likely that the shift occurred during the creation of the PDF file.
Undoubtedly, the manuscript is much better after the correction, but I still have some comments on this version of the manuscript. My main observation is that there is still a lack of information on the composition of the gut microbiome and a comparison of its major taxa in healthy individuals and individuals with autism spectrum disorders, as well as the impact of this microbiome on autism. In a manuscript with the name indicated by the authors and in a journal devoted to the use of microorganisms, this section should occupy one of the central places and be sufficiently weighty. An applied microbiology journal cannot contain publications that are not related to microbiology, and therefore this review contains mainly information on neurotransmitters and biochemical processes that affect brain function.
Without adding data of the gut microbiome, analysis of key and signalling taxa in autistic disorders, the whole review is meaningless and does not correspond to the theme of the journal, as the review in this form is more related to biochemistry and neurobiology than to applied microbiology.
Author Response
Comments and Suggestions for Authors
Dear Authors,
Thank you for making changes to your publication. When I read the second version of your review, I had a small problem because the line numbering in the authors' response did not match the line numbering in the attached file, making it difficult to find the material mentioned in the response. It is likely that the shift occurred during the creation of the PDF file.
Undoubtedly, the manuscript is much better after the correction, but I still have some comments on this version of the manuscript. My main observation is that there is still a lack of information on the composition of the gut microbiome and a comparison of its major taxa in healthy individuals and individuals with autism spectrum disorders, as well as the impact of this microbiome on autism. In a manuscript with the name indicated by the authors and in a journal devoted to the use of microorganisms, this section should occupy one of the central places and be sufficiently weighty. An applied microbiology journal cannot contain publications that are not related to microbiology, and therefore this review contains mainly information on neurotransmitters and biochemical processes that affect brain function.
Without adding data of the gut microbiome, analysis of key and signalling taxa in autistic disorders, the whole review is meaningless and does not correspond to the theme of the journal, as the review in this form is more related to biochemistry and neurobiology than to applied microbiology.
ANSWER
We greatly appreciate the time you spent reviewing the manuscript. Your insightful suggestion to include a chapter on the gut microbial composition in individuals with ASD has significantly enhanced the content of our work. The addition of the chapter is reflected in lines 650-774. Thank you for enriching our manuscript!
Reviewer 2 Report
Comments and Suggestions for AuthorsAlthough authors have made substantial improvements to the manuscript, however a table for highlighting particular microbial groups that are predominant in autism patients than normal individuals is still lacking. Since the focus of the manuscript "Effect of Gut microbiome... on autism" therefore, i suggest the authors that addition of a table highlighting relevant microbes will be appealing to journal readers.
Author Response
Comments and Suggestions for Authors
Although authors have made substantial improvements to the manuscript, however a table for highlighting particular microbial groups that are predominant in autism patients than normal individuals is still lacking. Since the focus of the manuscript "Effect of Gut microbiome... on autism" therefore, i suggest the authors that addition of a table highlighting relevant microbes will be appealing to journal readers.
ANSWER
Thank you for taking the time to review the manuscript. We opted to include a schematic figure rather than an additional table focusing on the gut's microbial composition, as we believe it is more visually appealing to readers (lines 757-774).
Reviewer 3 Report
Comments and Suggestions for AuthorsThe paper was well organised again.
Author Response
Dear Reviewer,
We would like to thank you for improving and acknowledging the quality of our study.
Round 3
Reviewer 1 Report
Comments and Suggestions for AuthorsDear authors,
Thank you for the changes that have significantly improved the manuscript and made it more complete. In this form, the manuscript conforms to the stated title, purpose and thematic direction of the journal.
And yet I still have a couple of minor comments:
1. In the section “3. Composition of the gut microbiota in ASD”, all names of bacterial types and genera should be written in italics.
2. The inscriptions with the names of bacteria in the figure “Figure 3. The composition of the gut microbiota in ASD” must also be written in italics.
Author Response
Dear reviewer,
Thank you for performing your last revision and final comments to our manuscript
Comments:
- In the section “3. Composition of the gut microbiota in ASD”, all names of bacterial types and genera should be written in italics.
- The inscriptions with the names of bacteria in the figure “Figure 3. The composition of the gut microbiota in ASD” must also be written in italics.
Answer:
In section 3 we made all the names of bacterial types in italics l.447-557
For figure 3 thank you for the proposal but in this case, italics will not help the reader to process the written information.
