Many people commonly consume foods rich in fiber to promote weight loss and prevent chronic diseases such as diabetes and cancer.
However, in some individuals — especially those with a silent vascular malformation — high-purity fiber consumption may increase the risk of liver cancer, according to new research from the University of Toledo.
This discovery is detailed in a research paper published in the journal Gastrointestinal Diseasesbuilding on UToledo’s growing area of research expertise, where our gut plays an underappreciated role in the origin of disease.
“We have been working for a long time on the idea that all diseases start 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 advances this concept. It also provides clues that may help identify individuals at risk of developing liver cancer and may enable us to reduce this risk through simple dietary modifications.”
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Four years ago, Vijay Kumar’s team published a major research paper in the journal cell which found that a high percentage of mice with defects in the immune system developed liver cancer after being fed a diet fortified with inulin.
Inulin, a fermentable plant fiber, is available in supermarkets as a health-promoting prebiotic. It is also a common ingredient in processed foods.
While inulin boosts the metabolic health of most who consume it, Vijay Kumar and colleagues discovered that one in 10 apparently healthy standard test mice developed liver cancer after eating the insulin-containing diet.
“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 fibers, but we only now understand why mice were developing such an aggressive cancer.”
The new study offers an obvious explanation — and it may have implications beyond lab animals.
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.
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.
Portemic remittances in humans are relatively rare – the documented incidence 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.
Theorizing that elevated bile acid levels might serve as a viable marker of 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 developed liver cancer, their blood levels of bile acid were twice as high as in the men who did not develop liver cancer. A statistical analysis also found that individuals with the highest levels of bile acid in their blood had a more than fourfold increase in the risk of developing liver cancer.
The research team also sought to examine the relationship between fiber consumption, bile acid levels, and liver cancer in humans.
While current epidemiological studies do not differentiate between soluble and insoluble fiber, researchers can consider fiber consumption in concert with blood bile acids.
There are two main types of natural dietary fiber, soluble and insoluble. Soluble fiber is fermented by gut bacteria into short-chain fatty acids. Insoluble fiber passes through the digestive system unchanged.
Interestingly, the researchers found that high fiber intake reduced the risk of liver cancer by 29% in those whose serum bile acid levels were in the lowest quartile of the sample.
However, in men whose blood bile acid levels placed them in the top quartile of the sample, high fiber intake increased the risk of liver cancer by 40%.
Taken together, Yeoh and Vijay-Kumar say the results point to 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.
“Bile acids in the blood can be measured by a simple blood test that was developed over 50 years ago. However, the test is usually only done in some pregnant women,” said Vijay Kumar. “Based on our findings, we believe this simple blood test should be incorporated into routinely performed health monitoring screening measurements.”
And while researchers don’t widely argue against the health-promoting benefits of fiber, they do urge attention to the type of fiber some individuals eat, underscoring the importance of personalized nutrition.
“Not all fiber is created equal, and not all fiber is good for everyone in general,” Yeoh said. “People with liver problems associated with excess bile acids should be careful about refined, fermentable fiber.” “If you have a leaky liver, you have to be careful about what you eat, because what you eat will be treated differently.”
The interruption of liver cells from absorbing bile acid after a paracetamol overdose reduces liver damage
Beng San Yue et al., Shunt-induced hepatocellular cholestasis et al., Gastrointestinal Diseases (2022). DOI: 10.1053 / j.gastro.2022.08.033
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