UT-Microbiome Consortium, Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
Graduate Program in Immunology and Infectious Diseases, Pennsylvania State University, State College, PA 16802, USA.
Cell. 2018 Oct 18;175(3):679-694.e22. doi: 10.1016/j.cell.2018.09.004.
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.
膳食纤维可被肠道细菌发酵为短链脂肪酸（SCFA），这些脂肪酸被认为广泛具有促进健康的作用。因此，摄入此类膳食纤维可改善代谢综合征。然而，将可溶膳食纤维菊粉而非不可溶膳食纤维纳入成分明确的饮食中，会诱发黄疸型肝细胞癌（HCC）。这种 HCC 依赖于肠道微生物群，在多种肠道失调的小鼠中观察到，但在无菌或抗生素处理的小鼠中则没有观察到。此外，富含菊粉的高脂肪饮食可诱导野生型（WT）小鼠发生肠道菌群失调和 HCC。菊粉诱导的 HCC 通过胆汁淤积、肝细胞死亡的早期发生，随后在肝脏中发生中性粒细胞炎症而进展。发酵的药理学抑制或发酵细菌的耗竭可显著减少肠道中的 SCFA 并预防 HCC。用考来烯胺预防胆汁酸重吸收也可预防此类 HCC。因此，尽管有其益处，但应谨慎地在食物中添加可发酵纤维，因为它可能会增加 HCC 的风险。
