The health benefits of dietary soluble fiber are well established, but according to researchers at the University of Toledo, the source of that fiber makes all the difference: artificially enriching a diet with soluble fiber can cause liver cancer if insoluble fiber is not also consumed.
Dietary soluble fiber promotes good health because it is fermented by gut bacteria into short-chain fatty acids. These acids reduce the symptoms of metabolic syndrome, a co-occurring constellation of conditions—excess abdominal fat and high blood pressure, blood sugar, and cholesterol—that increase an individual's risk of diabetes, heart disease, and stroke.
To investigate whether soluble fiber would ameliorate symptoms of metabolic syndrome in mice, the researchers fed the mice a high-fat diet enriched with inulin, a highly refined soluble fiber which is FDA-approved as a pre-biotic supplement and is commonly added to processed foods. The inulin's effectiveness was confirmed when 40% of the mice lost weight. However, it also had an unexpected side effect: many of those same mice developed hepatocellular carcinoma (HCC), a cancer of the liver, by the end of the six-month study.
"The findings shook us, but at the same time we recognized their potential importance and accepted the challenge of exploring how processed dietary soluble fiber was inducing liver cancer," commented Matam Vijay-Kumar, PhD, senior author of the study published in the journal Cell. Dr. Vijay-Kumar is the director of The University of Toledo Microbiome Consortium and an associate professor in the university's Department of Physiology and Pharmacology.
The mice that developed HCC had dysbiosis, an imbalance of bacteria in the gut. The progression of HCC involved early onset of cholestasis—a reduction or stoppage of bile flow—and death of hepatocytes, followed by neutrophilic inflammation in the liver. Development of HCC was dependent on the microbiota; it did not occur in mice that were free of germs or that were treated with antibiotics. Pharmacologically inhibiting the inulin's fermentation process or depleting the fermenting bacteria significantly reduced intestinal short-chain fatty acids, preventing HCC. Preventing reabsorption of bile acids with cholestyramine also protected against the development of HCC.
"Strikingly, feeding beta-acids to inulin-fed mice averted liver cancer, which further reinforces our hypothesis that gut bacterial dysmetabolism [is] primarily driving liver cancer in these mice," commented co-lead author Vishal Singh, PhD, a Crohn's and Colitis Foundation Fellow at The University of Toledo.
Replacing inulin with cellulose, an insoluble fiber, also halted the formation of HCC. The fact that cellulose could not be fermented by gut bacteria, noted co-lead author Beng San Yeoh, a graduate student in Dr. Vijay-Kumar's lab, is a finding that "again highlights the link between bacterial fermentation of soluble fiber and liver cancer development in these mice."
Overall, the researchers remark in their study, despite the benefits of soluble fiber, the use of fermentable fiber to enrich food "should be approached with great caution" due to the increased risk of HCC.
"We fully appreciate that the fibers present in whole foods like fruits and vegetables are healthy," stated Dr. Vijay-Kumar. "Because of that, fortifying or adding purified fiber to processed food sounds logical. However, our results suggest it may in fact be dangerous." Noting that the soluble fibers added to foods are chemically processed and have been extracted from sources such as chicory root—the source of the inulin used in this experiment—that are not part of a natural meal, he said, "We don't know how the body responds to these processed fibers."
"Our study is going against the conventional wisdom of what people think, that fiber is good, no matter how they get it," Dr. Vijay-Kumar concluded. "We do not want to promote that fiber is bad. Rather, we highlight that fortifying processed foods with refined soluble fiber may not be safe or advisable to certain individuals with gut bacterial overgrowth or dysbiosis, whose abnormal fermentation of this fiber could increase the susceptibly to liver cancer."
For More Information
Singh V, Yeoh BS, Chassaing B, et al (2018). Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell, 175(3):679-694.E22. DOI:10.1016/j.cell.2018.09.004