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PreprintCC BY-NC-NDbioRxiv

A strong-to-weak interaction shift during microbiome succession is coupled to colonizer-dependent antimicrobial resistance

  1. 1University of Montreal

Abstract

The outcome of ecological succession is often attributed to the characteristics of the invader or the resident community, but rarely to how the community's interaction network reorganizes during assembly. Here, we track intraspecific lineage dynamics and infer time-resolved community interaction networks using Dynamic Covariance Mapping during ecological invasion of the mouse gut by a chromosomally barcoded, spectinomycin-resistant Escherichia coli K12 colonizer. The network is initially dominated by strong, predominantly inhibitory interactions, but as community diversity recovers, the distribution of interaction strengths contracts toward zero, producing a community increasingly dominated by weak and near-neutral interactions. The dominant eigenvalue of the DCM-inferred interaction matrix moves toward marginal stability predicted for dynamically assembling ecological networks. This pattern replicates across eight independent mice in two experimental cohorts, at both inter- and intra-species resolution. The ecological transition coincides with the reproducible resurgence of Paenibacillaceae to high relative abundance and persistent coexistence with E. coli under continued spectinomycin pressure. Whole-genome sequencing of recovered Paenibacillus macerans isolates identifies recurrent mutations in ribosomal protein S5 region associated with spectinomycin binding and strongly implicating this variant in resistance. Strikingly, under antibiotic pressure but without E. coli K12 invasion, resident Paenibacillaceae never blooms, indicating that expansion of the resistant population depends on the ecological context established by the colonizer. These findings show that gut microbiome succession is accompanied by a reproducible transition from strong toward weak interactions and link this network reorganization to the colonizer-dependent ecological benefit of antimicrobial resistance.

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BibTeX
@misc{gencel2026strongtoweak,
  title = {{A strong-to-weak interaction shift during microbiome succession is coupled to colonizer-dependent antimicrobial resistance}},
  author = {M. Gencel and C. Matta and G. M. Cofino and A. Menendez and S. Ramanathan and S. Bershtein and C. Hui and A. Serohijos},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.31.748276},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748276v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - A strong-to-weak interaction shift during microbiome succession is coupled to colonizer-dependent antimicrobial resistance
AU  - M. Gencel
AU  - C. Matta
AU  - G. M. Cofino
AU  - A. Menendez
AU  - S. Ramanathan
AU  - S. Bershtein
AU  - C. Hui
AU  - A. Serohijos
PY  - 2026
DA  - 2026/08/31
PB  - bioRxiv
DO  - 10.64898/2026.08.31.748276
UR  - https://www.biorxiv.org/content/10.64898/2026.08.31.748276v1
AB  - The outcome of ecological succession is often attributed to the characteristics of the invader or the resident community, but rarely to how the community's interaction network reorganizes during assembly. Here, we track intraspecific lineage dynamics and infer time-resolved community interaction networks using Dynamic Covariance Mapping during ecological invasion of the mouse gut by a chromosomally barcoded, spectinomycin-resistant Escherichia coli K12 colonizer. The network is initially dominated by strong, predominantly inhibitory interactions, but as community diversity recovers, the distribution of interaction strengths contracts toward zero, producing a community increasingly dominated by weak and near-neutral interactions. The dominant eigenvalue of the DCM-inferred interaction matrix moves toward marginal stability predicted for dynamically assembling ecological networks. This pattern replicates across eight independent mice in two experimental cohorts, at both inter- and intra-species resolution. The ecological transition coincides with the reproducible resurgence of Paenibacillaceae to high relative abundance and persistent coexistence with E. coli under continued spectinomycin pressure. Whole-genome sequencing of recovered Paenibacillus macerans isolates identifies recurrent mutations in ribosomal protein S5 region associated with spectinomycin binding and strongly implicating this variant in resistance. Strikingly, under antibiotic pressure but without E. coli K12 invasion, resident Paenibacillaceae never blooms, indicating that expansion of the resistant population depends on the ecological context established by the colonizer. These findings show that gut microbiome succession is accompanied by a reproducible transition from strong toward weak interactions and link this network reorganization to the colonizer-dependent ecological benefit of antimicrobial resistance.
ER  -