Food and Behaviour Research

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Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer

Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Olvera RA, Lapek Jr JD., Zhang L, Wang W-B, Hao S, Flythe MD, Gonzalez DJ, Cani PD, Conejo-Garcia JR, Xiong N, Kennett MJ, Joe B, Patterson AD, Gewirtz AT, Vijay-Kumar M (2018) Cell 2018 Oct, 175, Issue 3:  679-694. 

Web URL: Read the abstract on Cell.com here

Abstract:

Highlights

  • Diet enriched with soluble, but not insoluble, fiber induced HCC in dysbiotic mice
  • Fiber-induced HCC displayed early onset of cholemia and hyperbilirubinemia
  • Soluble fiber-induced HCC was microbiota-dependent and transmissible to WT mice
  • Inhibition of gut fermentation and exclusion of dietary soluble fiber prevented HCC

Summary

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.

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