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Metagenome-guided culturomics for the targeted enrichment of gut microbes

Author

Listed:
  • Jeremy Armetta

    (Technical University of Denmark Kgs.
    Novonesis A/S)

  • Simone S. Li

    (Technical University of Denmark Kgs.
    The University of Queensland
    Monash University
    Monash University)

  • Troels Holger Vaaben

    (Technical University of Denmark Kgs.)

  • Ruben Vazquez-Uribe

    (Technical University of Denmark Kgs.
    VIB)

  • Morten O. A. Sommer

    (Technical University of Denmark Kgs.)

Abstract

The gut microbiome significantly impacts human health, yet cultivation challenges hinder its exploration. Here, we combine deep whole-metagenome sequencing with culturomics to selectively enrich for taxa and functional capabilities of interest. Using a modified commercial base medium, 50 growth modifications were evaluated, spanning antibiotics, physico-chemical conditions, and bioactive compounds. Whole-metagenome sequencing identified medium additives, like caffeine, that enhance taxa often associated with healthier subjects (e.g., Lachnospiraceae, Oscillospiraceae, Ruminococcaceae). We also explore the impact of modifications on the composition of cultured communities and establish a link between medium preference and microbial phylogeny. Leveraging these insights, we demonstrate that combinations of media modifications can further enhance the targeted enrichment of taxa and metabolic functions, such as Collinsella aerofaciens, or strains harboring biochemical pathways involved in dopamine metabolism. This streamlined, scalable approach unlocks the potential for selective enrichment, advancing microbiome research by understanding the impact of different cultivation parameters on gut microbes.

Suggested Citation

  • Jeremy Armetta & Simone S. Li & Troels Holger Vaaben & Ruben Vazquez-Uribe & Morten O. A. Sommer, 2025. "Metagenome-guided culturomics for the targeted enrichment of gut microbes," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55668-y
    DOI: 10.1038/s41467-024-55668-y
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    References listed on IDEAS

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    1. Michael Zimmermann & Maria Zimmermann-Kogadeeva & Rebekka Wegmann & Andrew L. Goodman, 2019. "Mapping human microbiome drug metabolism by gut bacteria and their genes," Nature, Nature, vol. 570(7762), pages 462-467, June.
    2. Stephen Nayfach & Zhou Jason Shi & Rekha Seshadri & Katherine S. Pollard & Nikos C. Kyrpides, 2019. "New insights from uncultivated genomes of the global human gut microbiome," Nature, Nature, vol. 568(7753), pages 505-510, April.
    3. Lisa Maier & Camille V. Goemans & Jakob Wirbel & Michael Kuhn & Claudia Eberl & Mihaela Pruteanu & Patrick Müller & Sarela Garcia-Santamarina & Elisabetta Cacace & Boyao Zhang & Cordula Gekeler & Tisy, 2021. "Unravelling the collateral damage of antibiotics on gut bacteria," Nature, Nature, vol. 599(7883), pages 120-124, November.
    4. Elizabeth A. Rettedal & Heidi Gumpert & Morten O.A. Sommer, 2014. "Cultivation-based multiplex phenotyping of human gut microbiota allows targeted recovery of previously uncultured bacteria," Nature Communications, Nature, vol. 5(1), pages 1-9, December.
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