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Depletion of microbiome-derived molecules in the host using Clostridium genetics.
Guo, Chun-Jun; Allen, Breanna M; Hiam, Kamir J; Dodd, Dylan; Van Treuren, Will; Higginbottom, Steven; Nagashima, Kazuki; Fischer, Curt R; Sonnenburg, Justin L; Spitzer, Matthew H; Fischbach, Michael A.
Afiliación
  • Guo CJ; Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA.
  • Allen BM; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Department of Medicine, Weill Cornell Medicine, NY 10021, USA.
  • Hiam KJ; Graduate Program in Biomedical Sciences, Departments of Otolaryngology and Microbiology and Immunology, Helen Diller Family Comprehensive Cancer Center, Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Dodd D; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Van Treuren W; Graduate Program in Biomedical Sciences, Departments of Otolaryngology and Microbiology and Immunology, Helen Diller Family Comprehensive Cancer Center, Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Higginbottom S; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Nagashima K; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Fischer CR; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Sonnenburg JL; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Spitzer MH; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Fischbach MA; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science ; 366(6471)2019 12 13.
Article en En | MEDLINE | ID: mdl-31831639
The gut microbiota produce hundreds of molecules that are present at high concentrations in the host circulation. Unraveling the contribution of each molecule to host biology remains difficult. We developed a system for constructing clean deletions in Clostridium spp., the source of many molecules from the gut microbiome. By applying this method to the model commensal organism Clostridium sporogenes, we knocked out genes for 10 C. sporogenes-derived molecules that accumulate in host tissues. In mice colonized by a C. sporogenes for which the production of branched short-chain fatty acids was knocked out, we discovered that these microbial products have immunoglobulin A-modulatory activity.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clostridium / Redes y Vías Metabólicas / Microbioma Gastrointestinal / Edición Génica / Interacciones Microbiota-Huesped Límite: Animals Idioma: En Revista: Science Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clostridium / Redes y Vías Metabólicas / Microbioma Gastrointestinal / Edición Génica / Interacciones Microbiota-Huesped Límite: Animals Idioma: En Revista: Science Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos