Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge

Shuangshuang Wan; Peijun You; Qikai Shi; Hui Hu; Lu Zhang; Leyang Chen; Ziyi Wu; Shan Lin; Xiaojun Song; Yongneng Luo; Yaxuan Wang; Feng Ju; Dazhi Jin; Yu Chen

doi:10.3389/fmicb.2024.1368194

Gut microbiome changes in mouse, Mongolian gerbil, and hamster models following Clostridioides difficile challenge

Front Microbiol. 2024 Apr 4:15:1368194. doi: 10.3389/fmicb.2024.1368194. eCollection 2024.

Authors

Shuangshuang Wan^{1

2}, Peijun You¹, Qikai Shi¹, Hui Hu^{1

2}, Lu Zhang³, Leyang Chen⁴, Ziyi Wu⁴, Shan Lin^{1

5}, Xiaojun Song⁶, Yongneng Luo^{1

2}, Yaxuan Wang⁷, Feng Ju³, Dazhi Jin^#^{1

2}, Yu Chen^#^{1

2}

Affiliations

¹ School of Laboratory Medicine, Hangzhou Medical College, Hangzhou, China.
² Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province, Hangzhou, China.
³ Environmental Microbiome and Biotechnology Laboratory, School of Engineering, Westlake University, Hangzhou, China.
⁴ School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China.
⁵ TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China.
⁶ Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, China.
⁷ National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, China.

^# Contributed equally.

Abstract

Introduction: Clostridioides difficile infection (CDI), as well as its etiology and pathogenesis, have been extensively investigated. However, the absence of suitable CDI animal models that reflect CDI symptoms and the associated gut microbiome changes in humans has limited research progress in this field. Thus, we aimed to investigate whether Mongolian gerbils, which present a range of human pathological conditions, can been used in studies on CDI. Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.

Methods: In this study, we infected Mongolian gerbils and two existing CDI model animals, mice and hamsters, with the hypervirulent ribotype 027 C. difficile strain, and comparatively analyzed changes in their gut microbiome composition via 16S rRNA gene sequencing.

Results: The results obtained showed that C. difficile colonized the gastrointestinal tracts of the three rodents, and after the C. difficile challenge, C57BL/6J mice did not manifest CDI symptoms and their intestines showed no significant pathological changes. However, the hamsters showed explosive intestinal bleeding and inflammation and the Mongolian gerbils presented diarrhea as well as increased infiltration of inflammatory cells, mucus secretion, and epithelial cell shedding in their intestinal tissue. Further, intestinal microbiome analysis revealed significant differences with respect to intestinal flora abundance and diversity. Specifically, after C. difficile challenge, the Firmicutes/Bacteroidetes ratio decreased for C57BL/6J mice, but increased significantly for Mongolian gerbils and hamsters. Furthermore, the abundance of Proteobacteria increased in all three models, especially in hamsters, while that of Verrucomicrobia only increased significantly in C57BL/6J mice and Mongolian gerbils. Our results also indicated that differences in the relative abundances of Lactobacillaceae and Akkermansia were primarily responsible for the observed differences in response to C. difficile challenge.

Conclusion: Based on the observed responses to C. difficile challenge, we concluded for the first time that the Mongolian gerbil could be used as an animal model for CDI. Additionally, the taxa identified in this study may be used as biomarkers for further studies on CDI and to improve understanding regarding changes in gut microbiome in CDI-related diseases.

Keywords: Akkermansia; Clostridioides difficile; Lactobacillaceae; Mongolian gerbils; gut microbiome; rodent models.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Medical Science and Technology Project of Zhejiang Province (2021KY639), the Natural Science Foundation of Zhejiang Province (LQ20H280002 and LXZ22H300001), the National Natural Science Foundation of China (82372299), the Scientific Research Fund of Zhejiang Provincial Education Department (Y201942763 and Y202045376), and the Basic Research Projects of Hangzhou Medical College (KYZD202004, KYQN202002, and KYYB2023003).