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Inulin / Chicory root causes liver cancer in mice?


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That URL did not work, although https://www.bioportfolio.com/news/article/3786455/Gut-Bacteria-Link-Dietary-Fiber-with-Liver-Cancer.html referred to it and referred to:

Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer.
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.
Cell. 2018 Oct 18;175(3):679-694.e22. doi: 10.1016/j.cell.2018.09.004.
PMID: 30340040
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.
bile acids


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Disturbing, as I've been consuming around a tablespoon of inulin per day in hot chocolate. I wonder if the dysbiosis would be ameliorated by something as simple as consumption of polyphenols. Selectively modulating gut bacteria seems easy enough to do for humans who consume a range of plants, but not for chow fed mice.

Edited by tea
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  • 1 year later...


On 11/20/2018 at 11:57 PM, BrianA said:

I eat some foods like Kind Bars that have a bit of chicory root added, now I'm questioning if that's a good idea?


Here's an important passage from the study cited by Al Pater above:


Consumption of a plant-based diet naturally abundant in fiber has been customarily associated with numerous health benefits. As such, it is presumed that enriching foods with fermentable fibers might be a practical means to improve the health of persons who consume highly refined foods that typically lack such fibers. Indeed, our published observations support this long and widely held notion. Specifically, we reported that mice consuming purified, compositionally defined diets (CDD) that lack fermentable fiber display gut atrophy, which is corrected by enrichment of such diets with inulin (Chassaing et al., 2015b). The administration of inulin to mice also improves metabolic parameters and protects against obesity (Zou et al., 2018).

However, further study has led us to appreciate that consumption of processed foods enriched with purified fibers may have dire consequences in certain contexts. For instance, we observed that mice consuming inulin-enriched CDD develop severe colitis upon exposure to the chemical colitogen DSS (Miles et al., 2017). We herein report that prolonged feeding of fermentable fiber-enriched CDD to mice with pre-existing microbiota dysbiosis such as, but by no means limited to, T5KO mice, resulted in development of cholestatic HCC.

In contrast, there were no indications of liver disease in T5KO mice, that consumed similar amounts of inulin added to grain-based rodent chow (data not shown), which is a relatively unrefined conglomerate of food scraps that has classically served as the standard diet for rodents used in research. These results suggest that the dietary context (i.e., refined or unrefined diet) in which a fermentable fiber is consumed is of great importance and, in particular, caution against enriching highly refined foods with fermentable fibers.     https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232850/

( On T5KO mice, see  https://www.sciencedirect.com/science/article/pii/S155041311500515X )

(Also note that according to the study's authors,  "the adverse effects of fermentable fiber [are] not restricted to inulin alone, but broadly applicable to other types of soluble fibers, including pectin and FOS.")

I'm  highly skeptical that in a normal healthy human dietary context (WFPB),  consuming a moderate amount of chicory is going to be carcinogenic.

Edited by Sibiriak
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