A new study led by Francis Crick Institute researchers shows that mice fed on a diet rich in indole-3-carbinol (I3C) — a secondary plant metabolite produced in vegetables of the Brassica genus, including cabbage, cauliflower, and brussels sprouts — were protected from gut inflammation and colon cancer. The findings appear in the journal Immunity.
“We studied genetically modified mice that cannot produce or activate a protein called the aryl hydrocarbon receptor (AhR) — which acts as an environmental sensor, passing signals to immune cells and epithelial cells in the gut lining to protect us from inflammatory responses to the trillions of gut bacteria — in their guts, and found that they readily developed gut inflammation which progressed to colon cancer,” said study first author Dr. Amina Metidji, from the Francis Crick Institute.
“However, when we fed them a diet enriched with I3C, they did not develop inflammation or cancer. Interestingly, when mice whose cancer was already developing were switched to the I3C-enriched diet, they ended up with significantly fewer tumors which were also more benign.”
By studying both mice and mouse gut organoids (‘mini guts’ made from stem cells), Dr. Metidji and colleagues found that AhR is vital for repairing damaged epithelial cells.
Without AhR, intestinal stem cells fail to differentiate into specialized epithelial cells that absorb nutrients or generate protective mucus. Instead, they divide uncontrollably which can ultimately lead to colon cancer.
“Seeing the profound effect of diet on gut inflammation and colon cancer was very striking,” said study co-lead author Dr. Gitta Stockinger, also from the Francis Crick Institute.
“We often think of colon cancer as a disease promoted by a Western diet rich in fat and poor in vegetable content, and our results suggest a mechanism behind this observation. Many vegetables produce chemicals that keep AhR stimulated in the gut.”
“We found that AhR-promoting chemicals in the diet can correct defects caused by insufficient AhR stimulation. This can restore epithelial cell differentiation, offering resistance to intestinal infections and preventing colon cancer.”
“These findings are a cause for optimism; while we can’t change the genetic factors that increase our risk of cancer, we can probably mitigate these risks by adopting an appropriate diet with plenty of vegetables.”
As well as correcting altered AhR dependent gene expression, dietary I3C also had a surprising effect on unmodified mice with normal AhR expression.
While normal mice fed on standard or I3C-enriched food did not develop tumors during the study, those fed on a ‘purified control diet’ did.
“Normal mice on the purified control diet developed colon tumors within 10 weeks, whereas mice on the standard chow didn’t develop any,” said study co-lead author Dr. Chris Schiering, of Imperial College London.
“This suggests that even without genetic risk factors, a diet devoid of vegetable matter can lead to colon cancer.”
“This study in mice suggests that it’s not just the fiber contained in vegetables like broccoli and cabbage that help reduce the risk of bowel cancer, but also molecules found in these vegetables too. This adds to the evidence that a healthy diet, rich in vegetables, is important,” said Cancer Research UK’s Professor Tim Key, who was not involved in the study.
“Further studies will help find out whether the molecules in these vegetables have the same effect in people, but in the meantime there are already plenty of good reasons to eat more vegetables.”
Amina Metidji et al. The Environmental Sensor AHR Protects from Inflammatory Damage by Maintaining Intestinal Stem Cell Homeostasis and Barrier Integrity. Immunity, published online August 14,2018; doi: 10.1016/j.immuni.2018.07.010