Cancer Cells Dividing

Diets high in processed fibers may increase the risk of cancer

The findings highlight the need for routine testing of serum bile acid levels as well as caution when individuals with elevated blood bile acid levels consume fibre.

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

Many people often consume foods rich in fiber to promote weight loss and protect against chronic diseases such as cancer and diabetes.

However, consuming high-purity fiber may increase the risk of liver cancer in some people, especially those with silent vascular malformations, according to a recent study from the University of Toledo.

The result described in a report published in the journal Gastrointestinal Diseasesadds to UToledo’s expanding body of knowledge about the underappreciated role our gut plays in the origin of disease.

“We have been working for a long time on the idea that all diseases begin in the gut,” said Dr. Matam Vijay Kumar, professor in the Department of Physiology and Pharmacology at the College of Medicine and Life Sciences and senior author of the research paper. . This study makes a notable advance for this concept. It also provides clues that may help identify individuals at risk of developing liver cancer and potentially enable us to reduce this risk through simple dietary modifications.”

Matam Vijay Kumar and Bing San Yoh

From left, Dr. Matam Vijay Kumar, Professor in the Department of Physiology and Pharmacology, and Dr. Peng San Yeoh, Postdoctoral Fellow. Credit: University of Toledo

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Vijay Kumar’s team has published a major paper in the journal cell In 2018, it revealed that a large proportion of mice with defects in the immune system developed liver cancer after eating a diet fortified with inulin.

Inulin is a fermentable, refined vegetable fiber sold in supermarkets as a health-promoting prebiotic. In addition, it is often found in processed foods.

Vijay Kumar and colleagues found that about one in ten healthy, normal laboratory rats developed liver cancer after eating the insulin-containing diet, despite the fact that insulin promotes metabolic health in the majority of those who consume it.

“This was very surprising, given the rarity of observation of liver cancer in mice,” said Vijay Kumar, who is also director of the UToledo Microbiome Consortium. “The results raised real questions about the potential risks of some of the refined fibres, but we are only now understanding why mice develop such an aggressive cancer.”

The new study offers an obvious explanation — and it may have implications beyond lab animals.

missing link

As the team continued their investigations, the researchers discovered that all of the mice that developed malignant tumors had high concentrations of bile acids in their blood due to a previously unnoticed birth defect called mitral portal shunt.

Normally, the blood leaving the intestines goes to the liver where it is filtered before returning to the rest of the body. When a portal shunt is present, blood is shunted from the gastrointestinal tract away from the liver and back to the body’s general blood supply.

The vascular dysfunction of the liver also allows the synthesis of bile acids continuously. These bile acids eventually leak out and enter the circulatory system instead of in the gut.

Blood diverted away from the liver contains high levels of microbial products that can stimulate the immune system and cause inflammation.

To check for this inflammation, which can be harmful to the liver, the mice react by developing a compensatory anti-inflammatory response that suppresses the immune response and reduces their ability to detect and kill cancer cells.

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

Remarkably, 100% of the mice with a high level of bile acids in their blood developed cancer when fed insulin. None of the mice with low bile acids developed cancer when fed the same diet.

“Dietary insulin is good at subduing inflammation, but it can be disrupted to cause immunosuppression, which is not good for the liver,” said Dr. Bing San Yu, a postdoctoral fellow and first author of the new research paper.

The high-impact publication demonstrates the groundbreaking research being conducted at UToledo, said Dr. Bina Gu, Distinguished University Professor and Chair of the Department of Physiology and Pharmacology, and co-author of the study.

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

Ramifications

Outside of the lab, UToledo’s research can provide insight that may help doctors identify people at risk of developing liver cancer years before any tumors form.

Portemological conversions in humans are relatively rare – the documented occurrence is only 1 in 30,000 people at birth. However, because they generally do not cause any noticeable symptoms, the true infection rate may be several times greater. Portal shunts also commonly develop after cirrhosis.

Endoscopy that elevated bile

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Any substance that when dissolved in water gives a pH of less than 7.0 or donates a hydrogen ion.

“data-gt-translate-attributes=”[{” 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


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