Researchers from the Francis Crick Institute in London, United Kingdom, found that keeping mice on a diet rich in a compound known as indole-3-carbinol (I3C) — which comes from such vegetables — prevented the animals’ intestines from becoming inflamed and developing colon cancer.
They report the study in a paper now published in the journal Immunity.
“Seeing the profound effect,” says study senior author Dr. Brigitta Stockinger, a group leader at the Francis Crick Institute, “of diet on gut inflammation and colon cancer was very striking.”
Our digestive system produces I3C when we eat vegetables from a “large and diverse group” of plants known as brassicas.
Brassicas include, but are not limited to: broccoli, cabbage, collards, Brussels sprouts, cauliflower, kale, kohlrabi, swede, turnip, bok choi, and mizuna.
Colon cancer typically starts as a growth, or polyp, in the lining of the colon or large intestine. It can take many years for the cancer to develop from a polyp and not all polyps become cancerous.
Cancer of the colon or rectum is the third most commonly diagnosed in both women and men in the United States, not counting skin cancer.
The American Cancer Society (ACS) estimate that there will be 97,220 new cases of diagnosed colon cancer in the U.S. in 2018.
‘Concrete evidence’ of hidden mechanism
Despite a lot of evidence about the benefits to our digestive system of a diet rich in vegetables, much of the underlying cell biology remains unknown.
The new findings are the first to give “concrete evidence” of how dietary I3C — through its effect on a cell protein known as aryl hydrocarbon receptor (AhR) — protects the gut from inflammation and cancer.
AhR has several roles, and for it to work properly, it has to be activated by a compound that binds to it uniquely. I3C is such a compound.
One of AhR’s jobs in the gut is to pick up environmental signals and pass them on to immune cells and other cells in the lining. These signals are important for protecting the digestive tract from inflammation-promoting signals that come from the “trillions of bacteria” that live in it.
Another important role that AhR plays is helping stem cells convert into specialized gut lining cells that produce protective mucus and help extract nutrients from food.
When AhR is absent or does not work properly, the stem cells do not convert into working cells in the gut lining but “divide uncontrollably.” Uncontrolled cell division may lead to abnormal growths that can become malignant, or cancerous.
Importance of ‘plant matter’ in diet
Dr. Stockinger and her colleagues saw that normal laboratory mice that ate “purified control diets” developed colon tumors within 10 weeks, while those that ate standard “chow” containing grains and other ingredients did not develop any.
Purified control diets are tightly controlled to include precise amounts of protein, fat, carbohydrate, fiber, minerals, and vitamins. They are designed to exactly match nutritional requirements without including germs, allergens, and other substances that might introduce spurious variables in experiments.
The new study suggests that because purified control diets contain less plant matter, they have fewer compounds that activate AhR, compared with standard chow diets or diets enriched with I3C.
Dr. Chris Schiering, of Imperial College London, remarks that “even without genetic risk factors,” it would seem that “a diet devoid of vegetable matter can lead to colon cancer.”
‘Significantly fewer tumors’
The researchers used mice and organoids, or “mini guts,” grown from mouse stem cells, in their experiments. These revealed that the ability of intestinal epithelial cells to replenish themselves and repair the gut lining after infection or chemical damage was “profoundly influenced” by AhR.
The team also found that genetically engineered mice whose intestinal epithelial cells had no AhR — or could not activate the protein — failed to control an infection from a gut bacterium called Citrobacter rodentium. The animals developed gut inflammation and then colon cancer.
“However, when we fed them a diet enriched with I3C, they did not develop inflammation or cancer,” remarks first author Dr. Amina Metidji, also of the Francis Crick Institute.
Additionally, notes Dr. Metidji, when they switched mice that were already developing colon cancer to a diet rich in I3C, they found that those animals developed “significantly fewer tumors” and that those tumors were less likely to be malignant.
In discussing their results, the researchers raise the issue of whether it is the high fat content or the low consumption of vegetables in high-fat diets that explains the link to colon cancer.
The scientists now expect to continue the work on I3C and AhR with organoids grown from human gut tissue extracted in biopsies. Eventually, they expect the work to lead to human trials.
“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.”
Dr. Brigitta Stockinger
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