2. Academic Validation
  3. A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response

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

  • Nat Commun. 2024 Apr 2;15(1):2842. doi: 10.1038/s41467-024-47075-0.
Huan Yang # 1,  Xiaoxiao Wu # 1,  Xiao Li # 1,  Wanqing Zang 1,  Zhou Zhou 1,  Yuan Zhou 1,  Wenwen Cui 2,  Yanbo Kou 3,  Liang Wang 4,  Ankang Hu 5,  Lianlian Wu 5,  Zhinan Yin 6,  Quangang Chen 5,  Ying Chen 1,  Zhutao Huang 5,  Yugang Wang 7,  Bing Gu 8 9
Affiliations

Affiliations

  • 1 Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 2 Xuzhou Center for Disease Control and Prevention, Xuzhou, Jiangsu, China.
  • 3 Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 4 Department of Clinical Laboratory Medicine, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 5 Center of Animal Laboratory, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 6 The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, Guangdong, China.
  • 7 Laboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China. wangyg@xzhmu.edu.cn.
  • 8 Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, China. gb20031129@163.com.
  • 9 Department of Clinical Laboratory Medicine, Guangdong Provincial People's Hospital, Southern Medical University, Guangzhou, Guangdong, China. gb20031129@163.com.
  • # Contributed equally.
PMID: 38565558 DOI: 10.1038/s41467-024-47075-0
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.

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