Abstract
Colorectal cancer (CRC) is the third most common form of cancer and poses a critical public health threat due to the global spread of westernized diets high in meat, cholesterol, and fat. Although the link between diet and colorectal cancer has been well established, the mediating role of the gut microbiota remains elusive. In this study, we sought to elucidate the connection between the gut microbiota, diet, and CRC through metagenomic analysis of bacteria isolated from the stool of CRC (n = 89) and healthy (n = 161) subjects. This analysis yielded a dozen genera that were significantly altered in CRC patients, including increased Bacteroides, Fusobacterium, Dorea, and Porphyromonas prevalence and diminished Pseudomonas, Prevotella, Acinetobacter, and Catenibacterium carriage. Based on these altered genera, we developed two novel CRC diagnostic models through stepwise selection and a simplified model using two increased and two decreased genera. As both models yielded strong AUC values above 0.8, the simplified model was applied to assess diet-based CRC risk in mice. Mice fed a westernized high-fat diet (HFD) showed greater CRC risk than mice fed a regular chow diet. Furthermore, we found that nonglutinous rice, glutinous rice, and sorghum consumption reduced CRC risk in HFD-fed mice. Collectively, these findings support the critical mediating role of the gut microbiota in diet-induced CRC risk as well as the potential of dietary grain intake to reduce microbiota-associated CRC risk. Further study is required to validate the diagnostic prediction models developed in this study as well as the preventive potential of grain consumption to reduce CRC risk.
Highlights
Colorectal cancer (CRC) is the third most common cancer with the fourth highest cancer mortality in the world
The amount and composition of secreted extracellular vesicles is not static, and we have shown through metagenomic analysis that alterations in gut microbiota EVs are associated with a variety of conditions, such as inflammatory bowel disease and tight junction permeability[17,18]
Carriage of Gammaproteobacteria and Betaproteobacteria affiliated with Proteobacteria was significantly lower in the CRC patient group than in the healthy control group, while Bacilli and Fusobacteriia were significantly higher (p < 0.05) (Fig. 2a)
Summary
Colorectal cancer (CRC) is the third most common cancer with the fourth highest cancer mortality in the world. Yang et al Experimental & Molecular Medicine (2019) 51:117 are characterized by higher Prevotella abundance than African American counterparts with an increased risk of CRC development and diets high in red meat and fat, suggesting that gut bacteria play a role in dietary CRC risk[7]. An HFD is known to increase intestinal permeability, which in turn raises the level of gut microbiota-associated lipopolysaccharide (LPS)-induced local inflammation, and both phenomena that have been independently associated with CRC9,10. Leptin has been demonstrated to induce carcinogenesis by increasing the proliferation of colon cancer cells in vitro[13]. These findings demonstrate one example of the complex network of the interactions among diet, the gut microbiota, and CRC and highlight the mediating role of the gut microbiota
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.
