Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Singh, V; Yeoh, BS; Chassaing, B; Xiao, X; Saha, P; Aguilera Olvera, R; Lapek, 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

Published Date

  • October 18, 2018

Published In

Volume / Issue

  • 175 / 3

Start / End Page

  • 679 - 694.e22

PubMed ID

  • 30340040

Pubmed Central ID

  • PMC6232850

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2018.09.004


  • eng

Conference Location

  • United States