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Dietary fat, bile acid metabolism and colorectal cancer
Seminars in Cancer Biology ( IF 14.5 ) Pub Date : 2020-10-16 , DOI: 10.1016/j.semcancer.2020.10.003
Soeren Ocvirk 1 , Stephen J D O'Keefe 2
Affiliation  

Colorectal cancer (CRC) risk is predominantly driven by environmental factors, in particular diet. A high intake of dietary fat has been implicated as a risk factor inducing the formation of pre-neoplastic lesions (e.g., adenomatous polyps) and/or exacerbating colonic tumorigenesis. Recent data attributed the tumor-promoting activity of high-fat diets to their effects on gut microbiota composition and metabolism, in particular with regard to bile acids. Bile acids are synthesized in the liver in response to dietary fat and facilitate lipid absorption in the small intestine. The majority of bile acids is re-absorbed during small intestinal transit and subjected to enterohepatic circulation. Bile acids entering the colon undergo complex biotransformation performed by gut bacteria, resulting in secondary bile acids that show tumor-promoting activity. Excessive dietary fat leads to high levels of secondary bile acids in feces and primes the gut microbiota to bile acid metabolism. This promotes an altered overall bile acid pool, which activates or restricts intestinal and hepatic cross-signaling of the bile acid receptor, farnesoid X receptor (FXR). Recent studies provided evidence that FXR is a main regulator of bile acid-mediated effects on intestinal tumorigenesis integrating dietary, microbial and genetic risk factors for CRC. Selective FXR agonist or antagonist activity by specific bile acids depends on additional factors (e.g., bile acid concentration, composition of bile acid pool, genetic instability of cells) and, thus, may differ in healthy and tumorigenic conditions in the intestine. In conclusion, fat-mediated alterations of the gut microbiota link bile acid metabolism to CRC risk and colonic tumorigenesis, exemplifying how gut microbial co-metabolism affects colon health.



中文翻译:

膳食脂肪、胆汁酸代谢与结直肠癌

结直肠癌 (CRC) 风险主要受环境因素驱动,尤其是饮食。膳食脂肪的高摄入量被认为是诱导形成前肿瘤病变(例如,腺瘤性息肉)和/或加剧结肠肿瘤发生的危险因素。最近的数据将高脂饮食的促肿瘤活性归因于它们对肠道微生物群组成和代谢的影响,特别是在胆汁酸方面。胆汁酸在肝脏中合成以响应膳食脂肪并促进小肠中的脂质吸收。大多数胆汁酸在小肠运输过程中被重新吸收并进入肝肠循环。进入结肠的胆汁酸经历肠道细菌进行的复杂生物转化,产生具有促肿瘤活性的次级胆汁酸。过多的膳食脂肪会导致粪便中的次级胆汁酸含量升高,并促使肠道微生物群进行胆汁酸代谢。这促进了整体胆汁酸池的改变,从而激活或限制了胆汁酸受体法尼醇 X 受体 (FXR) 的肠道和肝脏交叉信号传导。最近的研究提供的证据表明,FXR 是胆汁酸介导的肠道肿瘤发生作用的主要调节因子,整合了 CRC 的饮食、微生物和遗传风险因素。特定胆汁酸的选择性 FXR 激动剂或拮抗剂活性取决于其他因素(例如,胆汁酸浓度、胆汁酸库的组成、细胞的遗传不稳定性),因此,在肠道的健康和致瘤条件下可能会有所不同。综上所述,

更新日期:2020-10-16
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