A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response

Huan Yang, Xiaoxiao Wu, Xiao Li, Wanqing Zang, Zhou Zhou, Yuan Zhou, Wenwen Cui, Yanbo Kou, Liang Wang, Ankang Hu, Lianlian Wu, Zhinan Yin, Quangang Chen, Ying Chen, Zhutao Huang, Yugang Wang () and Bing Gu ()
Additional contact information
Huan Yang: Xuzhou Medical University
Xiaoxiao Wu: Xuzhou Medical University
Xiao Li: Xuzhou Medical University
Wanqing Zang: Xuzhou Medical University
Zhou Zhou: Xuzhou Medical University
Yuan Zhou: Xuzhou Medical University
Wenwen Cui: Xuzhou Center for Disease Control and Prevention
Yanbo Kou: Xuzhou Medical University
Liang Wang: Southern Medical University
Ankang Hu: Xuzhou Medical University
Lianlian Wu: Xuzhou Medical University
Zhinan Yin: Jinan University
Quangang Chen: Xuzhou Medical University
Ying Chen: Xuzhou Medical University
Zhutao Huang: Xuzhou Medical University
Yugang Wang: Xuzhou Medical University
Bing Gu: Xuzhou Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Antibiotic-induced dysbiosis is a major risk factor for Clostridioides difficile infection (CDI), and fecal microbiota transplantation (FMT) is recommended for treating CDI. However, the underlying mechanisms remain unclear. Here, we show that Tritrichomonas musculis (T.mu), an integral member of the mouse gut commensal microbiota, reduces CDI-induced intestinal damage by inhibiting neutrophil recruitment and IL-1β secretion, while promoting Th1 cell differentiation and IFN-γ secretion, which in turn enhances goblet cell production and mucin secretion to protect the intestinal mucosa. T.mu can actively metabolize arginine, not only influencing the host’s arginine-ornithine metabolic pathway, but also shaping the metabolic environment for the microbial community in the host’s intestinal lumen. This leads to a relatively low ornithine state in the intestinal lumen in C. difficile-infected mice. These changes modulate C. difficile’s virulence and the host intestinal immune response, and thus collectively alleviating CDI. These findings strongly suggest interactions between an intestinal commensal eukaryote, a pathogenic bacterium, and the host immune system via inter-related arginine-ornithine metabolism in the regulation of pathogenesis and provide further insights for treating CDI.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47075-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47075-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47075-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().