A new study led by Salk Institute scientists is revealing the danger of high-fat diets in driving colorectal cancer growth. The novel research is finding that these all too common diets upset the balance of bile acids in the intestine, triggering a hormonal effect that allows cancerous cells to thrive.
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Upsetting bile acid balance
The researchers are hoping the findings will help to avoid such dire conditions.
"This study provides a new way to lower inflammation, restore intestinal health and to dramatically reduced tumor progression," said Professor Ronald Evans, director of the Gene Expression Laboratory, Howard Hughes Medical Institute investigator and holder of Salk's March of Dimes Chair in Molecular and Developmental Biology.
The work was conducted in mouse test subjects and found that animals with an APC mutation saw their cancer develop faster when fed a high-fat diet. Carriers of APC mutations have a very high risk of colorectal cancer and researchers are saying that an unhealthy diet could be the second hit.
"It could be that when you're genetically prone to get colon cancer, something like a high-fat diet is the second hit," said study co-author Ruth Yu, a staff researcher in the Gene Expression Laboratory at Salk.
The culprit for this effect, argue the researchers, are the bile acids in the stomach. More specifically the problem lies with bile acids that hinder the activity of a protein called the Farnesoid X receptor (FXR).
This protein allows bile acids to send hormonal signals to intestinal stem cells. What the researchers uncovered was that types of bile acids known to interact with FXR increased at the same time as cancer did and that, furthermore, the presence of additional bile acids also accelerated cancer progression.
"We knew that high-fat diets and bile acids were both risk factors for cancer, but we weren't expecting to find they were both affecting FXR in intestinal stem cells," said Annette Atkins, a staff researcher at Salk and co-author of the study.
This is because the gut naturally seeks to repair itself with the aid of FXR. FXR is what ensures that that process remains steady and safe. However, when bile acids mess with FXR, stem cells start growing chaotically and accumulating DNA damage.
FexD to the rescue
"We saw a very dramatic increase in cancer growth correlated to bile acid,” said Michael Downes, a senior staff scientist at Salk and co-corresponding author of the study.
“Our experiments showed that maintaining a balance of bile acids is key to reducing cancer growth.”
Thanks to these results, the researchers were able to test a new potential cancer treatment: a molecule called FexD. Developed at Salk, this molecule seeks to activate FXR in intestinal stem cells.
So far, FexD seems to counteract the damage done by unbalanced bile acids in both mouse organ models and human colon cancer cell lines. More tests need to be done before the drug can be tested on humans but researchers say it is a promising option.
The study is published in the journal Cell.