Thank you for your interest in our work and the two question that I answer here on behalf of all authors.

a) The Authors wrote that " All eight bacterial strains making up the VSL # 3 product were provided individually by the manufacturer " and concluded that the "8 different strains present in the product" have been characterized genomically. This conclusion is not scientifically sound being flawed by a methodological point of view. To assert that the strains characterized genetically are the "8 different strains present in the product" the Authors should have isolated them from a commercially available sample of VSL#3. The Authors have just characterized 8 individual strains given to them by the manufacturer and have no evidence that the individual strains given to them for testing are identical to the strains utilized for manufacturing and present in the VSL#3 sachets.

ANSWER: The work described in the article was intended to thoroughly analyse the predicted function and safety of the strains present in the VSL#3 product by characterizing these genetically by whole genome sequencing. As we indicated clearly, we separately obtained all eight bacterial strains making up the VSL#3 product from the manufacturer (Actial Farmaceutical SRL, Rome, Italy) and we determined the individual genomes of these strains as to provide a baseline for future work. A next step could be the isolation of strains from the VSL#3 product formulation itself as suggested. We and others have reported this approach for several other single strain probiotic products such as Lactobacillus casei, Lactobacillus rhamnosus or Lactobacillus acidophilus (please see URLs below). However, for a complex multispecies product, this may not be the most appropriate approach and hence we rather would determine its metagenomic sequence and compare that with the individual genomic sequences we report in this publication - these studies are ongoing.
>
> http://onlinelibrary.wile...
> https://www.nature.com/ar...
> https://www.ncbi.nlm.nih....
>
>
> b) The Authors omitted to mention that many properties of the VSL#3 are not only strain-specific, but depend also from whom, where and how the product is manufactured. The strains grown with different media and methods have a different biochemical and immunological profile. Genomic identity is inadequate to guarantee the interchageability of products manufactured at different places with different media and techniques, especially if such products, like VSL#3, are aimed at the treatment of serious mdical conditions. Accordingly, Authors should have mentioned the published data which question the safety and efficacy of the new VSL#3 Italy-made that has replaced the original VSL#3 USA-made

ANSWER: The production process was not addressed in this study since that is impacting phenotypic properties rather than the genomes that we report in this study. However, the functionality of probiotic products continues to be of great interest. In the case of this multispecies product, this is highly relevant and we are also in the process of determining the metaproteomic content of the VSL#3 product to complement the baseline information on the VSL#3 genomes that we report in this publication.