2. Academic Validation
  3. Veillonella intestinal colonization promotes C. difficile infection in Crohn's disease

Veillonella intestinal colonization promotes C. difficile infection in Crohn's disease

  • Cell Host Microbe. 2025 Aug 19:S1931-3128(25)00291-4. doi: 10.1016/j.chom.2025.07.019.
Ziyu Yang 1,  Jilin Wang 2,  Yifan Chen 3,  Tianchi Chen 4,  Zhen Shen 4,  Yanan Wang 4,  Ying Jian 4,  Guoxiu Xiang 4,  Xiaowei Ma 4,  Na Zhao 4,  Yan Song 4,  Bisheng Shi 4,  Juanxiu Qin 4,  Qian Liu 4,  Zhijun Cao 5,  Michael Otto 6,  Min Li 7
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; School of Nursing, Shanghai Jiao Tong University, Shanghai 200025, China.
  • 2 Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
  • 3 Division of Cardiology, State Key Laboratory for Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
  • 4 Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
  • 5 Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China. Electronic address: caozj_renji@163.com.
  • 6 Pathogen Molecular Genetics Section, Laboratory of Bacteriology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: motto@niaid.nih.gov.
  • 7 Department of Laboratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China; School of Nursing, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: rjlimin@shsmu.edu.cn.
PMID: 40848719 DOI: 10.1016/j.chom.2025.07.019
Abstract

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.

Keywords

ASBT; Clostridioides difficile; Crohn's disease; Veillonella parvula; pathogenesis; spore germination.

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