Back to Search
Start Over
Bacteroides fragilis restricts colitis-associated cancer via negative regulation of the NLRP3 axis
- Source :
- Cancer Letters. 523:170-181
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Patients with persistent ulcerative colitis (UC) are at a higher risk of developing colitis-associated cancer (CAC). Previous studies have reported that intestinal microbiota disturbance plays an important role in the process of CAC development in patients with UC, indicating that targeted intervention of intestinal microbiota and its metabolites may be a potential therapeutic strategy. Gut microbiota in the process of colorectal cancer development in UC patients was analyzed using the gutMEGA database and verified in fecal samples. The abundance of Bacteroides fragilis reduced significantly in the process of colitis associated cancer development. Broad-spectrum antibiotics (BSAB) intervene with the intestinal microbiota of mice and accelerate the process of colon cancer development. However, gavage transplantation with B. fragilis can effectively reverse the effects of BSAB. In the intestinal tract, B. fragilis promotes the secretion of short-chain fatty acids (SCFAs). Subsequently, SCFAs, especially butyrate, negatively regulate the inflammatory signaling pathway mediated by NLRP3 to inhibit the activation of macrophages and the secretion of proinflammatory mediators such as IL-18 and IL-1β, reducing the level of intestinal inflammation and restricting CAC development. In conclusion, colonization with B. fragilis has been shown to be effective in ameliorating intestinal epithelial damage caused by chronic inflammation and preventing the development of colonic tumors. Thus, it can be a therapeutic intervention strategy with good clinical application prospects.
- Subjects :
- Male
Cancer Research
Colorectal cancer
Butyrate
Gut flora
Proinflammatory cytokine
Bacteroides fragilis
Mice
NLR Family, Pyrin Domain-Containing 3 Protein
Animals
Humans
Medicine
biology
business.industry
Macrophages
Cancer
Fatty Acids, Volatile
biology.organism_classification
medicine.disease
Ulcerative colitis
Gastrointestinal Microbiome
Mice, Inbred C57BL
Transplantation
Butyrates
Oncology
Immunology
Dysbiosis
Colitis, Ulcerative
Colitis-Associated Neoplasms
business
Subjects
Details
- ISSN :
- 03043835
- Volume :
- 523
- Database :
- OpenAIRE
- Journal :
- Cancer Letters
- Accession number :
- edsair.doi.dedup.....ec40feda3fa338d4c3a58966dcd5fa9b