| Autor: |
Tejada JN; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA., Walters WA; Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany., Wang Y; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA., Kordahi M; INSERM Team 'Mucosal Microbiota in Chronic Inflammatory Diseases', CNRS UMR 8104, Université Paris Cité, Paris, France.; Institut Pasteur, Université Paris Cité, INSERM, Microbiome-Host Interaction Group, Paris, France., Chassaing B; INSERM Team 'Mucosal Microbiota in Chronic Inflammatory Diseases', CNRS UMR 8104, Université Paris Cité, Paris, France.; Institut Pasteur, Université Paris Cité, INSERM, Microbiome-Host Interaction Group, Paris, France., Pickard J; Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA., Nunez G; Department of Pathology and Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA., Ley R; Department of Microbiome Science, Max Planck Institute for Biology, Tübingen, Germany., Gewirtz AT; Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. |
| Abstrakt: |
We sought to better understand how intestinal microbiota confer protection against Clostridioides difficile ( C. difficile ) infection (CDI). We utilized gnotobiotic altered Schaedler flora (ASF) mice, which lack the abnormalities of germfree (GF) mice as well as the complexity and heterogeneity of antibiotic-treated mice. Like GF mice, ASF mice were highly prone to rapid lethal CDI, without antibiotics, while very low infectious doses resulted in chronic CDI. Administering such chronic CDI mice an undefined preparation of Clostridia lowered C. difficile levels by several logs. Importantly, such resolution of CDI was associated with colonization of Lachnospiraceae. Fractionation of the Clostridia population to enrich for Lachnospiraceae led to the appreciation that its CDI-impeding property strongly associated with a specific Lachnospiraceae strain, namely uncultured bacteria and archaea (UBA) 3401. UBA3401 was recalcitrant to being propagated as a pure culture but could be maintained in ASF mice, wherein it comprised up to about 50% of the intestinal microbiota, which was sufficient to generate a high-quality genomic sequence of this bacterium. Sequence analysis and ex vivo study of UBA3401 indicated that it had the ability to secrete substance(s) that directly impeded C. difficile growth. Moreover, in vivo administration of UBA3401/ASF feces provided strong protection to C. difficile challenge. Thus, UBA3401 may contribute to and/or provide a means to study microbiota-mediated CDI resistance. |
