Ocvirk Sören, O'Keefe Stephen Jd
Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, S853 Scaife Hall, 3550 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
Curr Nutr Rep. 2017 Dec;6(4):315-322. doi: 10.1007/s13668-017-0219-5. Epub 2017 Nov 3.
To review the evidence for the tumorigenic effects of food-stimulated bile acids on the colon and interaction with the gut microbiota.
High-fat diets promote the hepatic synthesis of bile acids and increase their delivery to the colonic lumen. Here, they stimulate the growth and activity of 7α-dehydroxylating bacteria, which convert primary into secondary bile acids that show tumorigenic activity, especially deoxycholic acid (DCA). Fecal levels of secondary bile acids correlate with mucosal and metabolic markers of colorectal cancer (CRC) risk in high and low risk adult individuals and can be modified within a few weeks by dietary change. While gut bacteria regulate the bile acid pool via complex microbial biotransformation, bile acids alter the gut microbiota composition due to their antimicrobial properties. This mutual reaction induces altered bile acid pools and dysbiotic compositions of the gut microbiota that may show tumor-promoting activity of bile acids beyond their conversion to DCA.
Bile acids act as tumor promoters in the colon. Diet and the gut microbiota are most likely the key drivers that mediate and confer bile acid-associated tumorigenic activity. Bacterial conversion of bile acids in the colon has a significant impact on their tumorigenic activity, substantiating the hypothesis that diet affects CRC risk through its effects on colonic microbial metabolism.
综述食物刺激产生的胆汁酸对结肠的致癌作用以及与肠道微生物群相互作用的证据。
高脂饮食会促进肝脏胆汁酸的合成,并增加其向结肠腔的输送。在结肠中,它们会刺激7α-脱羟基化细菌的生长和活性,这些细菌将初级胆汁酸转化为具有致癌活性的次级胆汁酸,尤其是脱氧胆酸(DCA)。在高风险和低风险成年个体中,粪便中次级胆汁酸的水平与结直肠癌(CRC)风险的黏膜和代谢标志物相关,并且可以通过饮食改变在几周内得到改善。虽然肠道细菌通过复杂的微生物生物转化调节胆汁酸池,但胆汁酸因其抗菌特性会改变肠道微生物群的组成。这种相互作用会导致胆汁酸池改变和肠道微生物群的生态失调,这可能表明胆汁酸除了转化为DCA之外还具有促肿瘤活性。
胆汁酸在结肠中起到肿瘤促进剂的作用。饮食和肠道微生物群很可能是介导和赋予胆汁酸相关致癌活性的关键驱动因素。结肠中胆汁酸的细菌转化对其致癌活性有重大影响,证实了饮食通过影响结肠微生物代谢来影响CRC风险的假说。