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

Abstract

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.

Gut Microbes and Microbial Metabolites in Colorectal Cancer Complicated with Different Serum Albumin Levels

“…There are multiple studies on the microbial metabolites short chain fatty acids (SCFAs) in relation to CRC and nutrition [9,[39][40][41] . The metabolomics method including 124 microbial metabolites allows for a more comprehensive assessment of stool samples from CRC patients.…”

“…Many studies supported that gut microbes [5][6][7] and microbial metabolites [8,9] are involved in the occurrence and development of CRC. The main clinical symptoms of malnutrition include fatigue, emaciation, and edema, and it is caused by the consumption of carbohydrates, fats, and proteins.…”

A review of current and future food applications of natural hydrocolloids

“…The physiological roles of the SCFAs have been recently elucidated in in vivo studies. SCFAs influence immunity (D'Souza et al ., ) and cancer (Wang et al ., ) via cytokine production and controlling cell growth rate, respectively. A high‐fat diet with high butyrate showed increased energy expenditure and reduces obesity risk in mice (Lu et al ., ).…”

A Tool for the Treatment of Gastrointestinal Tumors: Micro- Ecological Immunotherapy

“…This is because colorectal cancer cells can use the glycolysis pathway to create an acidic environment in the gastrointestinal tract, which results in the production of high SCFAs by Propionibacterium freudenreichii [53][54][55][56]. SCFAs block the proliferation of colorectal cancer cells primarily in the G1 phase of cell division [57]. Bifidobacteria can also inhibit the growth of colorectal cancer cells by stopping the cell cycle and increasing alkaline phosphatase activity during G0/G1.…”