Diets ‘devoid of vegetable matter’ may cause colon cancer

A new study emphasizes the importance to gut health of eating plenty of vegetables such as cabbage, broccoli, and kale.
selection of greens
Eating brassicas such as collards, kale, and broccoli may protect against colon cancer.
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.

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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.