Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy

• Published in: Journal of cellular physiology Vol. 234; no. 10; pp. 17023 - 17049
• Main Authors: Wang, Gang, Yu, Yang, Wang, Yu‐Zhu, Wang, Jun‐Jie, Guan, Rui, Sun, Yan, Shi, Feng, Gao, Jing, Fu, Xing‐Li
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2019
• Subjects: Acetic acid; Animals; Anticancer properties; Cancer therapies; Chemical compounds; Colon; Colorectal cancer; colorectal cancers; Colorectal carcinoma; Colorectal Neoplasms - metabolism; Digestive system; Ecological effects; Energy sources; Fatty acids; Fatty Acids, Volatile - metabolism; Gastrointestinal Microbiome - physiology; Gastrointestinal tract; Glucose metabolism; Glycolysis; Glycolysis - physiology; Gut microbiota; Humans; Intestinal microflora; Intestine; Lactic acid; Metabolism; Microbiomes; Microbiota; Pharmacology; Propionic acid; SCFAs; Therapy; Transformed cells; Tumorigenesis; SCFAs; colorectal cancers; therapy; gut microbiota; glycolysis
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.28436

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short‐chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs‐mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy. Short‐chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch that escape absorption in the small intestine, and serve as a major source of energy for colonocytes. SCFAs are microbial‐derived metabolites, which are readily absorbed and used as an energy source by colonocytes. Several mechanisms have been proposed to underlie the anticancerous mechanisms of SCFAs. SCFAs reduce epithelial inflammation and trigger cancer cell apoptosis via p21 activity, providing an important defensive capacity against colorectal carcinogenesis.