Intra- and inter-species interactions drive early phases of invasion in mice gut microbiota

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Abstract

The stability and dynamics of ecological communities are dictated by interaction networks typically quantified at the level of species. 1–10 But how such networks are influenced by intra-species variation (ISV) is poorly understood. 11–14 Here, we use ~500,000 chromosomal barcodes to track high-resolution intra-species clonal lineages of Escherichia coli invading mice gut with the increasing complexity of gut microbiome: germ-free, antibiotic-perturbed, and innate microbiota. By co-clustering the dynamics of intra-species clonal lineages and those of gut bacteria from 16S rRNA profiling, we show the emergence of complex time-dependent interactions between E. coli clones and resident gut bacteria. With a new approach, dynamic covariance mapping (DCM), we differentiate three phases of invasion in susceptible communities: 1) initial loss of community stability as E. coli enters; 2) recolonization of some gut bacteria; and 3) recovery of stability with E. coli coexisting with resident bacteria in a quasi-steady state. Comparison of the dynamics, stability and fitness from experimental replicates and different cohorts suggest that phase 1 is driven by mutations in E. coli before colonization, while phase 3 is by de novo mutations. Our results highlight the transient nature of interaction networks in microbiomes driven by the persistent coupling of ecological and evolutionary dynamics.

One-Sentence Summary

High-resolution lineage tracking and dynamic covariance mapping (DCM) define three distinct phases during early gut microbiome invasion.

Article activity feed

  1. Such high-resolution chromosomal barcoding techniques

    It could be informative to specify where the barcodes have been introduced in E. coli's genomes. While this information can be found in the paper mentioned as reference 24, this information is worth restating here to prevent confusion with barcoded gene disruption libraries (for instance RB-TNSeq libraries).

  2. successfully colonized

    To help understand the different statements and conclusions about successful and unsuccessful colonization, the authors could define clearly what they mean 'colonization'. It is clear for the im cohort that E. coli doesn't survive, however what are the criteria to differentiate between a transient population versus an established population, especially in regards to the transit time in the mice gut.

  3. One mouse

    Have the authors characterized the microbiome of all the mice at T0 before the E. coli gavage to identify any different starting points in terms of community composition that could potentially influence the outcome of the colonization (for instance the presence of a couple of specific species that could promote horizontal gene transfer)

  4. These results highlight the stochasticity of transmission kinetics through the intestinal gut’s distinct “island” niches34,

    I can see this as being one possibility, but I'm not sure based on this data that this is the only possible explanation. It may be worth rephrasing to make this more of a possible explanation rather than a claim. It may also be worth briefly defining island niches- I tried looking at reference 34 but don't see this term in there.

  5. The bacterial community dynamics are unperturbed by the entry of E. coli into the community (Fig. 1g)

    I see that the overall diversity of the community does not seem to be impacted, but does this necessarily mean that the community dynamics don't change? In other words, does the relative composition change but remain equally diverse or does the composition not change and therefore diversity doesn't change? This may be reflected in your frequency weighting/q metrics but it may be worth stating more clearly here or just having a supp figure showing the relative abundance plots from the 16s sequencing.

  6. The dominant cluster, C1, was always grouped with Lachnospiraceae, whereas two other low-frequency clusters, C7 and C8 grouped persistently with Lactobacillaceae, the canonical member of gut microbiota (Fig. 2c). Interestingly, it was previously shown in invasion studies of pathogenic strains of E. coli and Lachnospiraceae that these bacteria utilize similar sugars and thrive in the same environment37.

    It could be interesting to also know something about the species/ strain diversity of the resident bacteria, and whether these clusters interact with specific species/strains

  7. The dominant cluster, C1, was always grouped with Lachnospiraceae, whereas two other low-frequency clusters, C7 and C8 grouped persistently with Lactobacillaceae, the canonical member of gut microbiota (Fig. 2c). Interestingly, it was previously shown in invasion studies of pathogenic strains of E. coli and Lachnospiraceae that these bacteria utilize similar sugars and thrive in the same environment37.

    It could be interesting to also know something about the species/ strain diversity of the resident bacteria, and whether these clusters interact with specific species/strains

  8. These results highlight the stochasticity of transmission kinetics through the intestinal gut’s distinct “island” niches34,

    I can see this as being one possibility, but I'm not sure based on this data that this is the only possible explanation. It may be worth rephrasing to make this more of a possible explanation rather than a claim. It may also be worth briefly defining island niches- I tried looking at reference 34 but don't see this term in there.

  9. One mouse

    Have the authors characterized the microbiome of all the mice at T0 before the E. coli gavage to identify any different starting points in terms of community composition that could potentially influence the outcome of the colonization (for instance the presence of a couple of specific species that could promote horizontal gene transfer)

  10. successfully colonized

    To help understand the different statements and conclusions about successful and unsuccessful colonization, the authors could define clearly what they mean 'colonization'. It is clear for the im cohort that E. coli doesn't survive, however what are the criteria to differentiate between a transient population versus an established population, especially in regards to the transit time in the mice gut.

  11. The bacterial community dynamics are unperturbed by the entry of E. coli into the community (Fig. 1g)

    I see that the overall diversity of the community does not seem to be impacted, but does this necessarily mean that the community dynamics don't change? In other words, does the relative composition change but remain equally diverse or does the composition not change and therefore diversity doesn't change? This may be reflected in your frequency weighting/q metrics but it may be worth stating more clearly here or just having a supp figure showing the relative abundance plots from the 16s sequencing.

  12. Such high-resolution chromosomal barcoding techniques

    It could be informative to specify where the barcodes have been introduced in E. coli's genomes. While this information can be found in the paper mentioned as reference 24, this information is worth restating here to prevent confusion with barcoded gene disruption libraries (for instance RB-TNSeq libraries).