“Be sure to eat dark leafy greens” is a common refrain from nutritionists, smug diet gurus, and – for many of us – our mothers. And while it may be well-known that this category of vegetables is excellent for one’s health, the molecular machinations behind these protective effects remained mysterious.
But now, a team of researchers from the Francis Crick Institute in London have shown how indole-3-carbinol (I3C) – a chemical produced in large concentrations in plants of the mustard genus Brassica (such as kale, broccoli, cabbage, and brussels sprouts) – helps prevent the intestinal inflammation that leads to colon cancer.
Past research in mice has revealed that blocking the activity of a type of cellular protein called the aryl hydrocarbon receptor (AhR) causes the animals to develop deadly infections and intestinal tumors. In both mice and humans, AhRs act as environmental sensors, and are thus found on cells that get exposed to elements to the outside world: the skin, lung, and gut. In the layer of the intestinal lining that separates the body’s own cells from the trillions of bacteria that colonize the internal surface, the receptor mediates signaling pathways involved in repairing damaged tissue, preventing infection by pathogenic bacteria, and suppressing an immune response against the many species of beneficial bacteria that constitute our microbiome.
In a series of experiments in genetically engineered live mice and mouse cell cultures, the Francis Crick team not only discovered how AhR oversees these essential intestinal functions – through the regulation of the stem cells that differentiate into intestine-lining cells – but they determined that I3C, which is one of many molecules that can bind to AhR, can activate AhR pathways when the receptor itself is absent or impaired. The results are published in the journal Immunity.
“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,” first author Dr Amina Metidji said in a statement. “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.”
Dr Metidji and her colleagues also noted that normal, non-modified lab mice who were fed a basic mouse chow went on to develop colon tumors within just 10 weeks, whereas those receiving either I3C-rich food or simply one with more vegetables did not. This suggests that I3C and other plant-based chemicals are essential for colon health – at least, in mice.
The next step will be to investigate whether these mechanisms work the same in humans.
“In the meantime, there’s certainly no harm in eating more vegetables!” added senior author Dr Gitta Stockinger.