Strain dropouts reveal interactions that govern the metabolic output of the gut microbiome

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  1. Table S1

    If the species of the community can be organized into niches (within the niche network mentioned in the first comment), it could also be informative to represent them organized as such, to eventually see where the species whose abundance is impacted by the presence/absence of Cs and Ch are directly or indirectly metabolically connected to them

  2. a niche rather than an individual strain.

    If the gut microbiome can be divided into niches (or a network of niches), do the authors know how many ‘niches’ can thus be defined (in the model community used in the paper), how they are connected and how would the bile acid niche fit into such network?

  3. In light of these results,

    This work and these results are really interesting and exciting. This whole story and its conclusions could nicely be summarized into a diagram to make it even easier to navigate and understand.

  4. Figure 2D

    How do the authors controlled for the species inoculation level? Inoculation level of a given species can also impact its final relative abundance. While in the Methods it seems that the inoculations are all done from the same species pools, aliquots have been frozen and thawed before inoculation, while the metagenomic analysis of the pool has been performed before freezing. So I am wondering if this could have introduced some inoculation differences and how the authors distinguish between potential inoculation effect versus interaction effect when comparing the relative abundance of the same species in the hCom1a experiment and the double dropout for instance? Would a comparison of abundance fold change (between Cecum and Inoculum) between 2 conditions lead to the same conclusions? For instance: comparing the abundance fold change of Ruminococcus obeum between Cecum and inoculum of the hCom1a condition to Ro abundance fold change (Cecum versus inoculum) in the double dropout condition.

  5. An unexpected impact of Cs on aromatic amino acid metabolism

    Have the authors considered looking at metatranscriptome modifications and untargeted metabolites profiles? That could provide an even broader insight into the modifications following the suppression of 1 or 2 strains, that may or may not lead to such drastic changes in community composition but rather in species physiology.

  6. Ruminococcus obeum (Ro), Ruminococcus bromii (Rb), Mitsuokella multacida (Mm), Roseburia intestinalis (Ri), and Eubacterium ventriosum (Ev) decreased

    Are these species part of the same niches? Are they part of upstream or downstream niches? Replacing them in a metabolic network could be interesting to highlight potential interactions.

  7. In light of these results,

    This work and these results are really interesting and exciting. This whole story and its conclusions could nicely be summarized into a diagram to make it even easier to navigate and understand.

  8. An unexpected impact of Cs on aromatic amino acid metabolism

    Have the authors considered looking at metatranscriptome modifications and untargeted metabolites profiles? That could provide an even broader insight into the modifications following the suppression of 1 or 2 strains, that may or may not lead to such drastic changes in community composition but rather in species physiology.

  9. Ruminococcus obeum (Ro), Ruminococcus bromii (Rb), Mitsuokella multacida (Mm), Roseburia intestinalis (Ri), and Eubacterium ventriosum (Ev) decreased

    Are these species part of the same niches? Are they part of upstream or downstream niches? Replacing them in a metabolic network could be interesting to highlight potential interactions.

  10. Figure 2D

    How do the authors controlled for the species inoculation level? Inoculation level of a given species can also impact its final relative abundance. While in the Methods it seems that the inoculations are all done from the same species pools, aliquots have been frozen and thawed before inoculation, while the metagenomic analysis of the pool has been performed before freezing. So I am wondering if this could have introduced some inoculation differences and how the authors distinguish between potential inoculation effect versus interaction effect when comparing the relative abundance of the same species in the hCom1a experiment and the double dropout for instance? Would a comparison of abundance fold change (between Cecum and Inoculum) between 2 conditions lead to the same conclusions? For instance: comparing the abundance fold change of Ruminococcus obeum between Cecum and inoculum of the hCom1a condition to Ro abundance fold change (Cecum versus inoculum) in the double dropout condition.

  11. Table S1

    If the species of the community can be organized into niches (within the niche network mentioned in the first comment), it could also be informative to represent them organized as such, to eventually see where the species whose abundance is impacted by the presence/absence of Cs and Ch are directly or indirectly metabolically connected to them

  12. a niche rather than an individual strain.

    If the gut microbiome can be divided into niches (or a network of niches), do the authors know how many ‘niches’ can thus be defined (in the model community used in the paper), how they are connected and how would the bile acid niche fit into such network?