A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response
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 mem...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-04-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47075-0 |
| _version_ | 1797219725686603776 |
|---|---|
| author | 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 Bing Gu |
| author_facet | 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 Bing Gu |
| author_sort | Huan Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T12:38:13Z |
| format | Article |
| id | doaj.art-463da6c679d241269bd0a0f658e564b4 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:38:13Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-463da6c679d241269bd0a0f658e564b42024-04-07T11:24:25ZengNature PortfolioNature Communications2041-17232024-04-0115111810.1038/s41467-024-47075-0A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune responseHuan Yang0Xiaoxiao Wu1Xiao Li2Wanqing Zang3Zhou Zhou4Yuan Zhou5Wenwen Cui6Yanbo Kou7Liang Wang8Ankang Hu9Lianlian Wu10Zhinan Yin11Quangang Chen12Ying Chen13Zhutao Huang14Yugang Wang15Bing Gu16Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityXuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityXuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityXuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityXuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityXuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityXuzhou Center for Disease Control and PreventionLaboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical UniversityDepartment of Clinical Laboratory Medicine, Guangdong Provincial People’s Hospital, Southern Medical UniversityCenter of Animal Laboratory, Xuzhou Medical UniversityCenter of Animal Laboratory, Xuzhou Medical UniversityThe Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan UniversityCenter of Animal Laboratory, Xuzhou Medical UniversityXuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityCenter of Animal Laboratory, Xuzhou Medical UniversityLaboratory of Infection and Immunity, Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical UniversityXuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical UniversityAbstract 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.https://doi.org/10.1038/s41467-024-47075-0 |
| spellingShingle | 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 Bing Gu A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response Nature Communications |
| title | A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response |
| title_full | A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response |
| title_fullStr | A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response |
| title_full_unstemmed | A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response |
| title_short | A commensal protozoan attenuates Clostridioides difficile pathogenesis in mice via arginine-ornithine metabolism and host intestinal immune response |
| title_sort | commensal protozoan attenuates clostridioides difficile pathogenesis in mice via arginine ornithine metabolism and host intestinal immune response |
| url | https://doi.org/10.1038/s41467-024-47075-0 |
| work_keys_str_mv | AT huanyang acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT xiaoxiaowu acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT xiaoli acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT wanqingzang acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT zhouzhou acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yuanzhou acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT wenwencui acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yanbokou acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT liangwang acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT ankanghu acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT lianlianwu acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT zhinanyin acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT quangangchen acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yingchen acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT zhutaohuang acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yugangwang acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT binggu acommensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT huanyang commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT xiaoxiaowu commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT xiaoli commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT wanqingzang commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT zhouzhou commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yuanzhou commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT wenwencui commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yanbokou commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT liangwang commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT ankanghu commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT lianlianwu commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT zhinanyin commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT quangangchen commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yingchen commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT zhutaohuang commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT yugangwang commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse AT binggu commensalprotozoanattenuatesclostridioidesdifficilepathogenesisinmiceviaarginineornithinemetabolismandhostintestinalimmuneresponse |