Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes
Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes
ABSTRACT The human gut pathogen Clostridioides difficile displays extreme genetic variability and confronts a changeable nutrient landscape in the gut. We mapped gut microbiota inter-species interactions impacting the growth and toxin production of diverse C. difficile strains in different nutrient environments. Although negative interactions impacting C. difficile are prevalent in environments promoting resource competition, they are sparse in an environment containing C. difficile-preferred carbohydrates. C. difficile strains display differences in interactions with Clostridium scindens and the ability to compete for proline. C. difficile toxin production displays substantial community-context dependent variation and does not trend with growth-mediated inter-species interactions. C. difficile shows substantial differences in transcriptional profiles in the presence of the closely related species C. hiranonis or C. scindens. In co-culture with C. hiranonis, C. difficile exhibits massive alterations in metabolism and other cellular processes, consistent with their high metabolic overlap. Further, Clostridium hiranonis inhibits the growth and toxin production of diverse C. difficile strains across different nutrient environments and ameliorates the disease severity of a C. difficile challenge in a murine model. In sum, strain-level variability and nutrient environments are major variables shaping gut microbiota interactions with C. difficile.
Vivas Eugenio I.、Diener Christian、Sulaiman Jordy Evan、Venturelli Ophelia S.、Qian Yili、Safdar Nasia、Thompson Jaron、Gibbons Sean M.
Gnotobiotic Animal Core Facility, University of Wisconsin-Madison||Department of Bacteriology, University of Wisconsin-MadisonInstitute for Systems BiologyDepartment of Biochemistry, University of Wisconsin-MadisonDepartment of Biochemistry, University of Wisconsin-Madison||Department of Chemical & Biological Engineering, University of Wisconsin-Madison||Department of Bacteriology, University of Wisconsin-Madison||Department of Biomedical Engineering, University of Wisconsin-MadisonDepartment of Biochemistry, University of Wisconsin-MadisonDivision of Infectious Disease, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison||Department of Medicine, William S. Middleton Veterans Hospital MadisonDepartment of Biochemistry, University of Wisconsin-Madison||Department of Chemical & Biological Engineering, University of Wisconsin-MadisonInstitute for Systems Biology||Department of Bioengineering, University of Washington||Department of Genome Sciences, University of Washington||eScience Institute, University of Washington
微生物学生物科学研究方法、生物科学研究技术基础医学
Vivas Eugenio I.,Diener Christian,Sulaiman Jordy Evan,Venturelli Ophelia S.,Qian Yili,Safdar Nasia,Thompson Jaron,Gibbons Sean M..Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes[EB/OL].(2025-03-28)[2025-05-23].https://www.biorxiv.org/content/10.1101/2024.04.13.589383.点此复制
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