The research, published in the journal Immunity, shows that mice fed on a diet rich in indole-3-carbinol – which is produced when we digest vegetables from the Brassica genus – were protected from gut inflammation and colon cancer.
While the health benefits of vegetables are well-established, many of the mechanisms behind them remain unknown.
This study offers the first concrete evidence of how I3C in the diet can prevent colon inflammation and cancer, by activating a protein called the aryl hydrocarbon receptor (AhR). AhR 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 bacteria that live in the gut.
“We studied genetically modified mice that cannot produce or activate AhR in their guts, and found that they readily developed gut inflammation which progressed to colon cancer,” said 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 tumours which were also more benign,” said Metidji.
By studying both mice and mouse gut organoids – ‘mini guts’ made from stem cells – the researchers found that AhR is vital for repairing damaged epithelial cells. Without AhR, intestinal stem cells fail to differentiate into specialised 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 Gitta Stockinger, Group Leader at the Francis Crick Institute in the UK. “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,” said Stockinger.
“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,” she said. “This can restore epithelial cell differentiation, offering resistance to intestinal infections and preventing colon cancer,” Stockinger said.
“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,” she said.