The paper by Ruichen Ring et al. proposes a method to simulate realistic microbiome data. The proposed strategy is named MB-GAN and it is based on a deep learning approach, more specifically on generative adversarial networks. The proposed solution is validated experimentally on a real case-control gut microbiome study composed by 396 samples. The simulated data have similar first- and second-order properties with respect to the original ones.

The topic involved in the manuscript is suitable for publication in this journal. Although applying deep learning in the microbiome field is intriguing, I have major concerns that need to be properly addressed before a possible publication of the paper: 1. Please specify better the utility of the proposed approach in generating simulated data. I suggest adding a practical example in which the generated simulated data can be really useful to address a specific microbiome-related problem. 2. What is the advantage in applying the proposed methodology with respect to the naive case in which original taxonomic profiles are generated by a simple random perturbation? I think in this case you would get profiles very similar to the original ones, but probably it would be something not really desired? How do you evaluate that the proposed methodology is really better than a random generation process? 3. The proposed methodology is not completely clear to me. Relative abundances are constrained values in the sense that their sum must be equal to 1 (or 100%). How is this accomplished by the proposed method? 4. The proposed method is validated on a single dataset. Please add more datasets in the evaluation part of the paper in order to evaluate robustness of the proposed methodology. 5. Does the proposed methodology depend from some free parameters? How do they affect the results? 6. What in terms of computational load of the proposed solution? Please add some considerations and an empirical evaluation if possible

Declaration of competing interests Please complete a declaration of competing interests, considering the following questions: Have you in the past five years received reimbursements, fees, funding, or salary from an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold any stocks or shares in an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold or are you currently applying for any patents relating to the content of the manuscript? Have you received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript? Do you have any other financial competing interests? Do you have any non-financial competing interests in relation to this paper? If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your reply is yes to any, please give details below.

I declare that I have no competing interests.

I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published. I agree to the open peer review policy of the journal.

Authors response to reviews: (https://drive.google.com/file/d/1UmBGLCVtqx5B5JNPBPDgSEL3_aQkVT3t/view?usp=sharing)

This a resubmission of a paper that I had previously reviewed in the same journal. I feel the authors have improved their manuscript in this revised version and answered properly to my previous concerns.

Declaration of competing interests Please complete a declaration of competing interests, considering the following questions: Have you in the past five years received reimbursements, fees, funding, or salary from an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold any stocks or shares in an organisation that may in any way gain or lose financially from the publication of this manuscript, either now or in the future? Do you hold or are you currently applying for any patents relating to the content of the manuscript? Have you received reimbursements, fees, funding, or salary from an organization that holds or has applied for patents relating to the content of the manuscript? Do you have any other financial competing interests? Do you have any non-financial competing interests in relation to this paper? If you can answer no to all of the above, write 'I declare that I have no competing interests' below. If your reply is yes to any, please give details below.

I declare that I have no competing interests.

I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published. I agree to the open peer review policy of the journal.