Bacteroides fragilis restricts colitis-associated cancer via negative regulation of the NLRP3 axis. (28th December 2021)

• Record Type: Journal Article
• Authors: Shao, Xinyu; Sun, Shishuo; Zhou, Yuqing; Wang, Huiyu; Yu, Yang; Hu, Tong; Yao, Yizhou; Zhou, Chunli
• Is Part Of: Cancer letters. Volume 523(2021)
• Page Start: 170
• Page End: 181
• Publication Date: 2021-12-28
• Subjects: Bacteroides fragilis -- Ulcerative colitis -- Colitis-associated cancer -- Butyrate -- Proinflammatory mediators; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2021.10.002
• Languages: English
• ISSNs: 0304-3835

Abstract

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. Highlights: Colonization with B. fragilis relieves intestinal inflammation, maintains intestinal homeostasis via regulating SCFAs. B. fragilis transplantation is effective in preventing intestinal epithelial damage and the development of CAC. B. fragilis FMT may be an intervention therapy strategy with good clinical application prospect. Butyrate negatively regulates the NLRP3 inflammatory pathway, to inhibit the secretion of proinflammatory mediators.