• 长期吃富含可溶纤维的饲料(ICD),可使肠道菌群失调的T5KO等免疫缺陷小鼠发生胆汁淤积、肝脏炎症和黄疸型肝癌(HCC),而不可溶纤维无此作用;
  • ICD诱导的HCC依赖于肠道菌群,可通过菌群转移令野生型小鼠发病;
  • 长期吃富含菊粉的高脂饲料,可使野生型小鼠发生菌群失调和HCC,增加T5KO小鼠HCC发病率,伴随肠道中纤维发酵菌和变形菌门增多;
  • 抑制肠内发酵生成SCFA、削减发酵细菌、不吃可溶纤维,或抑制胆汁酸再吸收,可预防上述HCC。
Cell [IF:36.216]

Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer



2018-10-18, Article

Abstract & Authors:展开

Dietary soluble fibers are fermented by gut bacteria into short-chain fatty acids (SCFA), which are considered broadly health-promoting. Accordingly, consumption of such fibers ameliorates metabolic syndrome. However, incorporating soluble fiber inulin, but not insoluble fiber, into a compositionally defined diet, induced icteric hepatocellular carcinoma (HCC). Such HCC was microbiota-dependent and observed in multiple strains of dysbiotic mice but not in germ-free nor antibiotics-treated mice. Furthermore, consumption of an inulin-enriched high-fat diet induced both dysbiosis and HCC in wild-type (WT) mice. Inulin-induced HCC progressed via early onset of cholestasis, hepatocyte death, followed by neutrophilic inflammation in liver. Pharmacologic inhibition of fermentation or depletion of fermenting bacteria markedly reduced intestinal SCFA and prevented HCC. Intervening with cholestyramine to prevent reabsorption of bile acids also conferred protection against such HCC. Thus, its benefits notwithstanding, enrichment of foods with fermentable fiber should be approached with great caution as it may increase risk of HCC.

First Authors:
Vishal Singh,Beng San Yeoh,Benoit Chassaing

Correspondence Authors:
Matam Vijay-Kumar

All Authors:
Vishal Singh,Beng San Yeoh,Benoit Chassaing,Xia Xiao,Piu Saha,Rodrigo Aguilera Olvera,John D Lapek Jr,Limin Zhang,Wei-Bei Wang,Sijie Hao,Michael D Flythe,David J Gonzalez,Patrice D Cani,Jose R Conejo-Garcia,Na Xiong,Mary J Kennett,Bina Joe,Andrew D Patterson,Andrew T Gewirtz,Matam Vijay-Kumar