Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes

Jordy Evan Sulaiman, Jaron Thompson, Yili Qian, Eugenio I. Vivas, Christian Diener, Sean M. Gibbons, Nasia Safdar and Ophelia S. Venturelli ()
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Jordy Evan Sulaiman: University of Wisconsin-Madison
Jaron Thompson: University of Wisconsin-Madison
Yili Qian: University of Wisconsin-Madison
Eugenio I. Vivas: University of Wisconsin-Madison
Christian Diener: Institute for Systems Biology
Sean M. Gibbons: Institute for Systems Biology
Nasia Safdar: University of Wisconsin-Madison
Ophelia S. Venturelli: University of Wisconsin-Madison

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract The human gut pathogen Clostridioides difficile displays substantial inter-strain genetic variability and confronts a changeable nutrient landscape in the gut. We examined how human gut microbiota inter-species interactions influence the growth and toxin production of various C. difficile strains across different nutrient environments. Negative interactions influencing C. difficile growth are prevalent in an environment containing a single highly accessible resource and sparse in an environment containing C. difficile-preferred carbohydrates. C. difficile toxin production displays significant community-context dependent variation and does not trend with growth-mediated inter-species interactions. C. difficile strains exhibit differences in interactions with Clostridium scindens and the ability to compete for proline. Further, C. difficile shows substantial differences in transcriptional profiles in co-culture with C. scindens or Clostridium hiranonis. C. difficile exhibits massive alterations in metabolism and other cellular processes in co-culture with C. hiranonis, reflecting their similar metabolic niches. C. hiranonis uniquely inhibits the growth and toxin production of diverse C. difficile strains across different nutrient environments and robustly ameliorates disease severity in mice. In sum, understanding the impact of C. difficile strain variability and nutrient environments on inter-species interactions could help improve the effectiveness of anti-C. difficile strategies.

Date: 2024
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DOI: 10.1038/s41467-024-51062-w

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