Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.
Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.
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DOI：
10.1016/j.cell.2018.09.004
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发表时间：
2018-10-18
期刊：
影响因子：
64.5
通讯作者：
Vijay-Kumar M
中科院分区：
文献类型：
--
作者：
Singh V;Yeoh BS;Chassaing B;Xiao X;Saha P;Aguilera Olvera R;Lapek JD Jr;Zhang L;Wang WB;Hao S;Flythe MD;Gonzalez DJ;Cani PD;Conejo-Garcia JR;Xiong N;Kennett MJ;Joe B;Patterson AD;Gewirtz AT;Vijay-Kumar M
膳食可溶性纤维被肠道细菌发酵成短链脂肪酸（SCFA），被认为是广泛的健康促进。因此，这种纤维的消耗改善代谢综合征。然而，将可溶性纤维菊粉，而不是不溶性纤维，到一个组成定义的饮食，诱导黄疸型肝细胞癌（HCC）。这种HCC是微生物群依赖性的，并且在多个菌株的生态失调小鼠中观察到，但在无菌或抗微生物药物治疗的小鼠中没有观察到。此外，在野生型（WT）小鼠中，食用富含菊粉的高脂肪饮食诱导了生态失调和HCC。菊粉诱导的HCC通过早期胆汁淤积、肝细胞死亡、随后肝脏嗜酸性炎症进展。药理学抑制发酵或消耗发酵细菌显着降低肠道SCFA和预防HCC。用消胆胺干预以防止胆汁酸的重吸收也可以预防此类HCC。因此，尽管它的好处，丰富的食物与发酵纤维应非常谨慎，因为它可能会增加肝癌的风险。肠道微生物群对膳食可溶性纤维的发酵失调诱导小鼠胆汁淤积、肝脏炎症和肝癌。
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. Dysregulated fermentation of dietary soluble fibers by gut microbiota induces cholestasis, hepatic inflammation, and liver cancer in mice.
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DOI：
10.1136/bmj.k322
发表时间：
2018-02-14
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Fiolet T;Srour B;Sellem L;Kesse-Guyot E;Allès B;Méjean C;Deschasaux M;Fassier P;Latino-Martel P;Beslay M;Hercberg S;Lavalette C;Monteiro CA;Julia C;Touvier M
通讯作者：
Touvier M
影响因子：
64.8
作者：
Chassaing B;Koren O;Goodrich JK;Poole AC;Srinivasan S;Ley RE;Gewirtz AT
通讯作者：
Gewirtz AT
Warburg效应决定了丁酸酯介导的组蛋白乙酰化和细胞增殖的机制。
影响因子：
16
作者：
Donohoe, Dallas R.;Collins, Leonard B.;Wali, Aminah;Bigler, Rebecca;Sun, Wei;Bultman, Scott J.
通讯作者：
Bultman, Scott J.
影响因子：
29
作者：
Donohoe DR;Garge N;Zhang X;Sun W;O'Connell TM;Bunger MK;Bultman SJ
通讯作者：
Bultman SJ
影响因子：
64.5
作者：
Kaiko GE;Ryu SH;Koues OI;Collins PL;Solnica-Krezel L;Pearce EJ;Pearce EL;Oltz EM;Stappenbeck TS
通讯作者：
Stappenbeck TS