Phocaeicola vulgatus shapes the long-term growth dynamics and evolutionary adaptations of Clostridioides difficile

Jordy Evan Sulaiman; Jaron Thompson; Pak Lun Kevin Cheung; Yili Qian; Jericha Mill; Isabella James; Hanhyeok Im; Eugenio I Vivas; Judith Simcox; Ophelia S Venturelli

doi:10.1016/j.chom.2024.12.001

Phocaeicola vulgatus shapes the long-term growth dynamics and evolutionary adaptations of Clostridioides difficile

Cell Host Microbe. 2024 Dec 23:S1931-3128(24)00446-3. doi: 10.1016/j.chom.2024.12.001. Online ahead of print.

Authors

Affiliations

¹ Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
² Department of Chemical & Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA.
³ Department of Electrical and Computer Engineering, University of Wisconsin-Madison, Madison, WI, USA.
⁴ Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
⁵ Department of Biomedical Engineering, Duke University, Durham, NC, USA.
⁶ Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA; Gnotobiotic Animal Core Facility, University of Wisconsin-Madison, Madison, WI, USA.
⁷ Howard Hughes Medical Institute, Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA.
⁸ Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USA; Department of Chemical & Biological Engineering, University of Wisconsin-Madison, Madison, WI, USA; Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA; Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: [email protected].

PMID: 39730002
DOI: 10.1016/j.chom.2024.12.001

Abstract

Clostridioides difficile can transiently or persistently colonize the human gut, posing a risk for infections. This colonization is influenced by complex molecular and ecological interactions with the human gut microbiota. By investigating C. difficile dynamics in human gut communities over hundreds of generations, we show patterns of stable coexistence, instability, or competitive exclusion. Lowering carbohydrate concentrations shifted a community containing C. difficile and the prevalent human gut symbiont Phocaeicola vulgatus from competitive exclusion to coexistence, facilitated by increased cross-feeding. In this environment, two key mutations in C. difficile altered its metabolic niche from proline to glucose utilization. These metabolic changes in C. difficile substantially impacted gut microbiota inter-species interactions and reduced disease severity in mice. In sum, interactions with P. vulgatus are crucial in shaping the long-term growth dynamics and evolutionary adaptations of C. difficile, offering key insights for developing anti-C. difficile strategies.

Keywords: Clostridioides difficile; Phocaeicola vulgatus; community assembly; computational modeling; cross-feeding; evolutionary adaptations; human gut microbiome; inter-species interactions.