Breakthrough Could Lead to More Effective Treatments for Colon Cancer, Other Gut Diseases

Colon cancer, Crohn’s disease, and other gut diseases could be better treated — or even prevented — thanks to a newly-discovered link between a cellular process called autophagy and inflammation. The findings of a research team at the University of Warwick are published in the journal Nature Communications.

Tusco et al find a link between inflammation and a common cellular process called autophagy. Image credit: University of Warwick.

Autophagy is an essential process whereby cells break down and recycle harmful or damaged elements within themselves to keep our bodies healthy.

According to the study, this process causes tissue inflammation when dysfunctional, which in turn leaves us susceptible to harmful diseases, particularly in the gut.

Understanding this link could lead to more effective treatments for gut diseases — such as colon cancer, irritable bowel syndrome, Crohn’s disease and ulcerative colitis — giving healthcare professionals the ability to target the root cause of these diseases, by regulating and controlling autophagy.

In the new study, Dr. Ioannis Nezis from the University of Warwick’s School of Life Sciences and co-authors identified a protein which is regulated by autophagy.

This protein, called Kenny, contains a motif of amino acids that causes itself to be broken down by autophagy.

When autophagy is dysfunctional, Kenny accumulates and causes inflammation.

The team identified this phenomenon in fruit flies (Drosophila melanogaster), by turning Kenny fluorescent — so it would be visible — and observing at a microscopic level that the protein was present in the cell where autophagy was occurring.

The scientists also noted that dysfunctional autophagy causes serious inflammation in fruit flies — particularly in the gut — which makes tissue inflamed, causing disease, and making the lifespan of a fruit fly half that of other flies.

“To prevent serious diseases of the gut caused by inflammation, it is necessary to find ways to control and regulate autophagy,” they said.

“Humans are in even more danger from the link between autophagy, inflammation, and a dysfunctional or diseased gut — because our bodies lack the regular motif of amino acids which Kenny uses in fruit flies, making its breakdown by autophagy difficult to control or regulate.”

“Understanding the molecular mechanisms of selective autophagy and inflammation will help to use interventions to activate the autophagic pathway to prevent inflammation and promote healthy well-being during the life course,” Dr. Nezis said.

“Natural compounds contained in fruits and vegetables like pomegranates, red grapes, pears, mushrooms, lentils, soybeans and green peas have been shown to activate autophagy, therefore inclusion of the above in our diet would help to prevent inflammation and alleviate the symptoms of gut diseases.”

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Radu Tusco et al. 2017. Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses. Nature Communications 8, article number: 1264; doi: 10.1038/s41467-017-01287-9