Cell:可溶性膳食纤维+坏菌群,可引发小鼠肝癌!
  • 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。
主编推荐语
mildbreeze
菊粉、果胶和低聚果糖等可溶膳食纤维,经肠道菌群发酵为短链脂肪酸(SCFA),被认为有广泛的促进健康功效,比如缓解代谢综合征等疾病。然而Cell发表的最新研究再次敲响警钟,提醒人们这类有益纤维,在特定情况下(比如肠道生态失调),可能对健康有害。该研究发现,在肠道菌群失调的小鼠中,长期吃大量可溶性纤维,可诱导小鼠发生胆汁淤积、肝脏炎症和肝癌,这种作用一定程度上由SCFA介导。未来需对可溶纤维的健康功效进行更全面的分析,不仅关注其有益的一面,也要注意特定条件下的潜在害处,充分检测不同情况下的安全用量,为个性化使用膳食纤维以改善健康,铺平道路。
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延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
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Cell [IF:36.216]

Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer

可溶纤维的失调微生物发酵诱导胆汁淤积性肝癌

10.1016/j.cell.2018.09.004

2018-10-18, Article

Abstract & Authors:展开

Abstract:收起
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

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