Diets High in Processed Fiber May Increase Cancer Risk

The study found that men who had a high fiber intake and high levels of bile acids in their blood had a 40% increased risk of liver cancer.

Many people use fiber-enriched foods to promote weight loss and prevent chronic diseases such as cancer and diabetes.

However, consuming highly refined fiber may increase the risk of liver cancer in certain people, especially those with a silent vascular deformity, according to a recent study from The University of Toledo.

The finding, described in a report published in the journal gastroenterologyadds to UToledo’s growing body of knowledge about the underappreciated role our gut plays in causing disease.

“We have worked for a long time on this idea that all diseases start in the gut,” said Dr. Matam Vijay-Kumar, a professor in the Department of Physiology and Pharmacology in the College of Medicine and Life Sciences and lead author of the study. Article. . “This study is a remarkable advance of that concept. It also provides clues that may help identify people at increased risk of liver cancer and potentially allow us to reduce that risk with simple dietary modifications.”

Expanding Research

Vijay-Kumar’s team published an important article in the journal Cell in 2018 that revealed that a large proportion of mice with defective immune systems developed liver cancer after receiving an inulin-fortified diet.

Inulin is a refined fermentable fiber of plant origin that is sold in supermarkets as a health-promoting prebiotic. Also, it is often found in processed foods.

Vijay-Kumar and colleagues found that about one in 10 normal, otherwise healthy laboratory mice developed liver cancer after consuming the inulin-containing diet, despite the fact that inulin promotes metabolic health in most of those who consume it.

“That was very surprising, given how infrequently liver cancer is seen in mice,” said Vijay-Kumar, who is also director of the UToledo Microbiome Consortium. “The findings raised real questions about the potential risks of certain refined fibers, but we only now understand why the mice were developing such aggressive cancer.”

The new study offers a clear explanation and may have implications that go beyond laboratory animals.

a missing link

As the team progressed in their research, the researchers discovered that all of the mice that developed malignant tumors had high concentrations of bile acids in their blood caused by a previously unrecognized birth defect called a portosystemic shunt.

Normally, blood leaving the intestines goes to the liver where it is filtered before returning to the rest of the body. When there is a portosystemic shunt, blood from the intestine bypasses the liver and returns to the body’s general blood supply.

The vascular defect also allows the liver to continuously synthesize bile acids. Those bile acids eventually spill out and go into circulation instead of going to the intestine.

The blood that is diverted from the liver contains high levels of microbial products that can stimulate the immune system and cause inflammation.

To control this inflammation, which can be damaging to the liver, the mice react by developing a compensatory anti-inflammatory response that dampens the immune response and reduces its ability to detect and kill cancer cells.

While all mice with excess bile acids in their blood were predisposed to liver injury, only those fed inulin progressed to hepatocellular carcinoma, a deadly primary liver cancer.

Surprisingly, 100% of the mice with high levels of bile acids in their blood developed cancer when fed inulin. None of the mice with low bile acid levels developed cancer when fed the same diet.

“Dietary inulin is good at reducing inflammation, but it can be subverted and cause immunosuppression, which is not good for the liver,” said Dr. Beng San Yeoh, a postdoctoral fellow and first author of the new paper.

Dr. Bina Joe, Distinguished University Professor and Chair of the Department of Physiology and Pharmacology, and co-author of the study, said the high-impact publication demonstrates the pioneering research being done at UToledo.

“The role of the gut and gut bacteria in health and disease is an exciting and important area of ​​research, and our team is providing new insights at the cutting edge of this field,” he said.

Transcendence

Beyond the laboratory, UToledo’s research could provide information that could help doctors identify people who are at increased risk of liver cancer years before tumors form.

Portosystemic shunts in humans are relatively rare: the documented incidence is only one in 30,000 people at birth. However, since they usually do not cause noticeable symptoms, the true incidence can be many times higher. Portosystemic shunt also commonly develops after liver cirrhosis.

Theorizing that high bile[{” attribute=””>acid levels might serve as a viable marker for liver cancer risk, Vijay-Kumar’s team tested bile acid levels in serum samples collected between 1985 and 1988 as part of a large-scale cancer prevention study.

In the 224 men who went on to develop liver cancer, their baseline blood bile acid levels were twice as high as men who did not develop liver cancer. Statistical analysis also found individuals with the highest blood bile acid levels had a more than four-fold increase in the risk of liver cancer.

The research team also sought to examine the relationship between fiber consumption, bile acid levels, and liver cancer in humans.

While existing epidemiological studies don’t differentiate between soluble and non-soluble fiber, researchers could look at fiber consumption in concert with blood bile acids.

There are two basic types of naturally occurring dietary fiber, soluble and insoluble. Soluble fibers are fermented by gut bacteria into short-chain fatty acids. Insoluble fibers pass through the digestive system unchanged.

Intriguingly, researchers found high total fiber intake reduced the risk of liver cancer by 29% in those whose serum bile acid levels were in the lowest quartile of their sample.

However, in men whose blood bile acid levels placed them in the top quarter of the sample, high fiber intake conferred a 40% increased risk of liver cancer.

Taken together, Yeoh and Vijay-Kumar say the findings suggest both the need for regular blood bile acid level testing and a cautious approach to fiber intake in individuals who know they have higher-than-normal levels of bile acids in their blood.

“Serum bile acids can be measured by a simple blood test developed over 50 years ago. However, the test is usually only performed in some pregnant women,” Vijay-Kumar said. “Based on our findings, we believe this simple blood test should be incorporated into the screening measurements that are routinely performed to monitor health.”

And while the researchers are not arguing broadly against the health-promoting benefits of fiber, they are urging attention to what kind of fiber certain individuals eat, underscoring the importance of personalized nutrition.

“All fibers are not made equal, and all fibers are not universally beneficial for everyone. People with liver problems associated with increased bile acids should be cautious about refined, fermentable fiber,” Yeoh said. “If you have a leaky gut liver, you need to be careful of what you eat, because what you eat will be handled in a different way.”

References: “Enterohepatic Shunt-Driven Cholemia Predisposes to Liver Cancer” by Beng San Yeoh, Piu Saha, Rachel M. Golonka, Jun Zou, Jessica L. Petrick, Ahmed A. Abokor, Xia Xiao, Venugopal R. Bovilla, Alexis C.A. Bretin, Jesús Rivera-Esteban, Dominick Parisi, Andrea A. Florio, Stephanie J. Weinstein, Demetrius Albanes, Gordon J. Freeman, Amira F. Gohara, Andreea Ciudin, Juan M. Pericàs, Bina Joe, Robert F. Schwabe, Katherine A. McGlynn, Andrew T. Gewirtz and Matam Vijay-Kumar, 18 August 2022, Gastroenterology.
DOI: 10.1053/j.gastro.2022.08.033

“Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer” by Vishal Singh, Beng San Yeoh, Benoit Chassaing, Xia Xiao, Piu Saha, Rodrigo Aguilera Olvera, John D. Lapek Jr., Limin Zhang, Wei-Bei Wang, Sijie Hao, Michael D. Flythe, David J. Gonzalez, Patrice D. Cani, Jose R. Conejo-Garcia, Na Xiong, Mary J. Kennett, Bina Joe, Andrew D. Patterson, Andrew T. Gewirtz and Matam Vijay-Kumar, 18 October 2018, Cell.
DOI: 10.1016/j.cell.2018.09.004