Secondary Bile Acids and Tumorigenesis in Colorectal Cancer

Abstract

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world and is a typical inflammatory tumor. In recent years, the incidence of CRC has been increasing year by year. There is evidence that the intake of high-fat diet and overweight are associated with the incidence of CRC, among which bile acids play a key role in the pathogenesis of the disease. Studies on the relationship between bile acid metabolism and the occurrence of CRC have gradually become a hot topic, improving the understanding of metabolic factors in the etiology of colorectal cancer. Meanwhile, intestinal flora also plays an important role in the occurrence and development of CRC In this review, the classification of bile acids and their role in promoting the occurrence of CRC are discussed, and we highlights how a high-fat diet affects bile acid metabolism and destroys the integrity of the intestinal barrier and the effects of gut bacteria.

Cholecystectomy promotes the development of colorectal cancer by the alternation of bile acid metabolism and the gut microbiota

“…In addition, these bacteria is able to establish a biological barrier in the gut via space-occupying effect, nutrient competition, and some secreted metabolites (113), which can decrease low-grade inflammatory response in the body and maintain the integrity of the intestinal wall. Motivating the intestine to create an effective immune defense system can modulate the absorption and conversion of sugar and fat in the intestinal tract, subsequently ameliorate glucose tolerance and oxidative stress, and lower blood glucose (114). Therefore, the homeostasis of gut microbiota plays significant roles in maintaining human health (115)(116)(117)(118).…”

Research on Gut Microbiota-Derived Secondary Bile Acids in Cancer Progression

“…Dietary fibers (from vegetables and fruits) can bind to LCA and aid in its excretion in stool. 16 More importantly, a variety of factors can regulate the absorption and synthesis of secondary BA by influencing gut bacteria levels, 23 such as dietary changes and antibiotics. The details will be described in section 4.1.3.…”

“…The FXR-mediated signaling pathways can regulate the metabolism of BAs, sugar and lipid and regulate inflammatory response. 23 …”

Effect of gut microbiota on colorectal cancer progression and treatment

“…Both the secondary bile acid products LCA and (deoxycholic acid) have been shown to promote CRC progression by activating the MAPK pathway through upregulation of urokinase-type plasminogen activator receptors and calcium signaling. 84 In addition, DCA has been shown to induce cancer via multiple processes, such as through the stimulation of ERK1/2, poly-ADP-ribose polymerase, and caspase-3 signaling. As a result, mechanisms such as DNA damage, ROS generation, and disruption of retinoblastoma protein levels cause cancer progression.…”

“…As a result, mechanisms such as DNA damage, ROS generation, and disruption of retinoblastoma protein levels cause cancer progression. 84 Lactate is a metabolite produced by gut microbiota and has an essential role in controlling angiogenic effect and TME. 85 Lactate has been shown to stimulate TME by creating an acidification environment, stimulating angiogenic responses to oxygen transfer, glucose delivery, and nutrition delivery, thereby promoting CRC invasion, proliferation, and migration.…”