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Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.

Publication ,  Journal Article
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 ...
Published in: Cell
October 18, 2018

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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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

October 18, 2018

Volume

175

Issue

3

Start / End Page

679 / 694.e22

Location

United States

Related Subject Headings

  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver Neoplasms
  • Inulin
  • Gastrointestinal Microbiome
  • Fermentation
  • Dysbiosis
  • Dietary Fiber
  • Diet, High-Fat
 

Citation

APA
Chicago
ICMJE
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Singh, V., Yeoh, B. S., Chassaing, B., Xiao, X., Saha, P., Aguilera Olvera, R., … Vijay-Kumar, M. (2018). Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell, 175(3), 679-694.e22. https://doi.org/10.1016/j.cell.2018.09.004
Singh, Vishal, Beng San Yeoh, Benoit Chassaing, Xia Xiao, Piu Saha, Rodrigo Aguilera Olvera, John D. Lapek, et al. “Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.Cell 175, no. 3 (October 18, 2018): 679-694.e22. https://doi.org/10.1016/j.cell.2018.09.004.
Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, et al. Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell. 2018 Oct 18;175(3):679-694.e22.
Singh, Vishal, et al. “Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.Cell, vol. 175, no. 3, Oct. 2018, pp. 679-694.e22. Pubmed, doi:10.1016/j.cell.2018.09.004.
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. Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer. Cell. 2018 Oct 18;175(3):679-694.e22.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

October 18, 2018

Volume

175

Issue

3

Start / End Page

679 / 694.e22

Location

United States

Related Subject Headings

  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver Neoplasms
  • Inulin
  • Gastrointestinal Microbiome
  • Fermentation
  • Dysbiosis
  • Dietary Fiber
  • Diet, High-Fat