Abstract
Background Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. Methods C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. Results The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. Conclusion Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.
Highlights
Colorectal cancer (CRC) is one of the most common cancers worldwide [1] and can be identified as sporadic, hereditary colorectal cancer (CRC), or colitis-associated cancer (CAC) [2, 3]
Mice in the control group grew well, while two mice in the azoxymethane/dextran sodium sulfate (AOM/dextran sodium sulfate (DSS)) group died while receiving DSS
Substantial evidence has demonstrated that gut dysbiosis and abnormal bile acid metabolism exist in many diseases such as CRC, nonalcoholic fatty liver disease, and diabetes
Summary
Colorectal cancer (CRC) is one of the most common cancers worldwide [1] and can be identified as sporadic, hereditary CRC, or colitis-associated cancer (CAC) [2, 3]. Patients with long-term inflammatory bowel disease (IBD), especially ulcerative colitis, can develop into intestinal cancer, known as CAC. Factors involving CAC development include immune response, epigenetic modification, intestinal inflammatory response, and gut dysbiosis [7, 8]. Previous studies have indicated the relevance between altered gut microbiota and risk of gastrointestinal diseases (such as IBD, CRC, and irritable bowel syndrome) [6, 9, 10]. Previous literature has shown that gut dysbiosis and bile acid metabolism disorder can promote CRC [10, 16]. Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
