Veillonella intestinal colonization promotes C. difficile infection in Crohn’s disease
Crohn's disease is a severe inflammatory disorder of the intestine for which there is no cure. Individuals suffering from Crohn's disease are at an increased risk of developing Clostridioides difficile infection (CDI), which considerably exacerbates symptoms. Using a prospective observational clinical study combined with animal models of intestinal inflammation, we show that intestinal colonization by Veillonella, an oral commensal, promotes CDI in Crohn's disease. In mice, Veillonella parvula suppresses expression of the main bile acid transporter, ASBT, thus preventing bile acid reabsorption. Similarly, Veillonella abundance is associated with increased bile acid metabolism in Crohn's disease patients. This increase in bile acid availability within the intestinal lumen triggers C. difficile germination. V. parvula expresses a highly pro-inflammatory lipopolysaccharide that triggers the transcription factors c-Jun and c-Fos regulating ASBT expression. These findings highlight that oral commensals can exacerbate intestinal disease, providing pathways to design therapeutics to treat CDI in Crohn's disease patients.
Authors
- Yulin Song (ORCID: https://orcid.org/0000-0002-2391-7466)
- Jilin Wang (ORCID: https://orcid.org/0000-0001-8385-253X)
- Yanan Wang (ORCID: https://orcid.org/0000-0002-8864-5609)
- Guoxiu Xiang
- Juanxiu Qin
- Bisheng Shi
- Zhijun Cao (ORCID: https://orcid.org/0000-0001-5429-484X)
- Michaël Otto (ORCID: https://orcid.org/0000-0002-2222-4115)
- Wenlong Yang (ORCID: https://orcid.org/0000-0003-3139-2767)
- Qian Liu (ORCID: https://orcid.org/0000-0001-8897-5117)
- Min Li (ORCID: https://orcid.org/0000-0003-2606-5315)
- Yifan Chen (ORCID: https://orcid.org/0000-0003-2080-843X)
- Ying Jian (ORCID: https://orcid.org/0000-0001-5185-2455)
- Na Zhao (ORCID: https://orcid.org/0000-0002-8417-7895)
- Xiaowei Ma (ORCID: https://orcid.org/0000-0003-3245-0930)
- Zhen Shen (ORCID: https://orcid.org/0000-0002-4056-3583)
- Tianchi Chen
Institutions
- Shanghai Jiao Tong University (CN)
- Renji Hospital (CN)
- Shanghai Cancer Institute (CN)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- Cell Host & Microbe
- Published
- 2025-08-22
- DOI
- https://doi.org/10.1016/j.chom.2025.07.019
- Citations
- 12
- Primary Topic
- Clostridium difficile and Clostridium perfringens research
- Type
- article
- Field-Weighted Citation Impact
- 16.75
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- National Natural Science Foundation of China
- Key Technologies Research and Development Program
- National Key Research and Development Program of China
- National Institute of Allergy and Infectious Diseases