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Fusobacterium varium Exacerbates Neutrophil-driven Intestinal Inflammation Associated with Succinate-SUCNR1-NF-κB
Qian Wang1, Han Xiao1, Wenxiu Liu1
1Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, 730030, China.
Inflammation
|June 19, 2026
Summary
Fusobacterium varium, a gut bacterium, worsens colitis by producing succinate. This metabolite recruits neutrophils, increasing intestinal inflammation in ulcerative colitis (UC) patients.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Ulcerative colitis (UC) involves gut microbial imbalance, but specific drivers of inflammation are unknown.
- Identifying bacterial pathobionts and their molecules is crucial for understanding UC pathogenesis.
Purpose of the Study:
- To identify bacterial species enriched in UC patients.
- To investigate the role of Fusobacterium varium (F. varium) and its metabolites in driving intestinal inflammation.
Main Methods:
- Metagenomic sequencing of fecal samples from UC patients and healthy controls.
- Colonization of germ-free mice with F. varium and induction of colitis.
- Analysis of bacterial culture supernatants and metabolite identification using mass spectrometry.
- In vitro studies on neutrophil activation and signaling pathways.
Main Results:
- F. varium was significantly enriched in UC patients.
- F. varium colonization exacerbated DSS-induced colitis in mice.
- Bacterial metabolite succinate was identified and found to promote colonic inflammation and neutrophil recruitment.
- Succinate activated NF-κB signaling in neutrophils via SUCNR1, inducing CXCL8 production.
Conclusions:
- F. varium contributes to intestinal inflammation in colitis.
- Succinate produced by F. varium exacerbates colitis, partly by recruiting neutrophils.
- Targeting succinate-mediated neutrophil recruitment may offer a therapeutic strategy for UC.
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