A study in mice shows that eating cruciferous vegetables -
including broccoli, kale and cauliflower - helps the immune system
to fight intestinal pathogens. The research might have implications
for people with inflammatory bowel diseases.
A protein called the aryl hydrocarbon receptor (AhR) plays a
crucial role in protecting us from external pollutants, toxins and
pathogens at barrier sites in our body such as the skin, lungs and
Studying the role of AhR in the gut, scientists at the Francis
Crick Institute have discovered that another protein, known as
Cyp1a1, regulates immunity in the gut by providing feedback on AhR
signalling by degrading the molecules that activate AhR - known as
However, too much Cyp1a1 can deplete AhR ligands altogether.
This could result in susceptibility to bacteria like pathogenicE. Coli and might play a role in conditions such as
inflammatory bowel disease.
Dr Stockinger, who led the work, says: "We already knew that AhR
deficiency causes many problems for the intestinal barrier. This is
because the immune cells that protect us from our trillions of
intestinal bacteria as well as from incoming intestinal pathogens
require signals through AhR for their survival.
"Molecules that activate AhR can come from our diet, but also
from our intestinal bacteria. Activation of AhR turns on enzymes
such as Cyp1a1. Normally the function of these enzymes is to
degrade the molecules that originally activated AhR and turn it
The researchers created mice with overactive Cyp1a1 - this
depleted their AhR ligands and resulted in less of the immune cells
that depend on AhR ligands. Unlike normal healthy mice, these mice
were unable to fight off an infection with Citrobacter bacteria -
the mouse version of human pathogenic E. Colibacteria.
Importantly, the increased activity of Cyp1a1 could be
controlled by adding nutrients found in cruciferous vegetables to
the food the mice were fed. This worked in two ways - by inhibiting
Cyp1a1 and by providing extra AhR-activating molecules.
Dr Stockinger says: "Previous work has mostly focused on the
consequences of complete absence of AhR itself in various cell
types, but this is not a scenario that will apply to humans as AhR
deficiency would not be compatible with life.
"However, as indicated in our study it is entirely conceivable
that some people have mutant Cyp1a1 enzymes that have abnormally
high activity. In humans, this could play a role in inflammatory
intestinal diseases where people with genetically determined
overactive Cyp1a1 would be particularly sensitive to infections.
Such people could potentially improve their intestinal immune
function by eating cruciferous vegetables such as broccoli, kale
and cauliflower, which are high in such Cyp1a1 inhibitors and
molecules that activate AhR."
The paper, Feedback control of AHR signalling regulates
intestinal immunity, is published in Nature.