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Cell. 2025 Mar 7:S0092-8674(25)00195-3. doi: 10.1016/j.cell.2025.02.010 Q145.62024

Genome-scale resources in the infant gut symbiont Bifidobacterium breve reveal genetic determinants of colonization and host-microbe interactions

婴儿肠道共生菌布氏嗜粘短链细菌的基因组规模资源揭示了定植和宿主-微生物相互作用的遗传决定因素 翻译改进

Anthony L Shiver  1, Jiawei Sun  1, Rebecca Culver  2, Arvie Violette  1, Char Wynter  1, Marta Nieckarz  3, Samara Paula Mattiello  4, Prabhjot Kaur Sekhon  5, Francesca Bottacini  6, Lisa Friess  7, Hans K Carlson  8, Daniel P G H Wong  9, Steven Higginbottom  10, Meredith Weglarz  11, Weigao Wang  12, Benjamin D Knapp  13, Emma Guiberson  14, Juan Sanchez  15, Po-Hsun Huang  16, Paulo A Garcia  16, Cullen R Buie  16, Benjamin H Good  17, Brian DeFelice  15, Felipe Cava  3, Joy Scaria  18, Justin L Sonnenburg  10, Douwe Van Sinderen  7, Adam M Deutschbauer  19, Kerwyn Casey Huang  20

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作者单位

  • 1 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • 2 Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • 3 Department of Molecular Biology and Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Science for Life Laboratory (SciLifeLab), Umeå University, Umeå 90187, Sweden.
  • 4 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA; College of Mathematics and Science, The University of Tennessee Southern, Pulaski, TN 38478, USA.
  • 5 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA; Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, OK 74074, USA; Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
  • 6 School of Microbiology, University College Cork, Cork, Ireland; Department of Biological Sciences, Munster Technological University, Cork, Ireland.
  • 7 School of Microbiology, University College Cork, Cork, Ireland; APC Microbiome Ireland, University College Cork, Cork, Ireland.
  • 8 Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • 9 Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
  • 10 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 11 Stanford Shared FACS Facility, Center for Molecular and Genetic Medicine, Stanford University, Stanford, CA 94305, USA.
  • 12 Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
  • 13 Biophysics Program, Stanford University, Stanford, CA 94305, USA.
  • 14 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Chemistry and Biochemistry, Middlebury College, Middlebury, VT 05753, USA.
  • 15 Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • 16 Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
  • 17 Department of Applied Physics, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • 18 Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, SD 57007, USA; Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, OK 74074, USA.
  • 19 Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
  • 20 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: kchuang@stanford.edu.

    • DOI: 10.1016/j.cell.2025.02.010 PMID: 40068681

    摘要 Ai翻译

    Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve. First, we generated a high-density randomly barcoded transposon insertion pool and used it to determine fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. Second, to enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1,462 genes. We leveraged these tools to reveal community- and diet-specific requirements for colonization and to connect the production of immunomodulatory molecules to growth benefits. These resources will catalyze future investigations of this important beneficial microbe.

    Keywords: RB-TnSeq; bifidobacteria; functional genomics; genome-scale metabolic reconstruction; genome-scale ordered mutant collection; glucose-phosphate stress; indole-3-lactic acid; infant microbiome; metabolomics; microbiome assembly.

    Keywords：genome-scale resources; genetic determinants; host-microbe interactions; infant gut symbiont

    关键词：基因组规模资源; 遗传决定因素; 宿主-微生物相互作用; 婴儿肠道共生菌

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    期刊名：Cell

    缩写：CELL

    ISSN：0092-8674

    e-ISSN：1097-4172

    IF/分区：45.6/Q1

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    Genome-scale resources in the infant gut symbiont Bifidobacterium breve reveal genetic determinants of colonization and host-microbe interactions