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Gut inflammation linked to broken cellular ‘recycling’

Gut inflammation may be linked to a common cellular process, researchers report.

The new research demonstrates that autophagy—an essential process whereby cells break down and recycle harmful or damaged elements within themselves to keep our bodies healthy—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.

autophagy gif
An animation showing autophagy. (Credit: U. Warwick)

“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,” says Ioannis Nezis, leader of the research and an assistant professor at the School of Life Sciences at the University of Warwick.

Nezis and colleagues have also identified a protein that autophagy regulates. Called Kenny, the protein 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 researchers identified this phenomenon in fruit flies, 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.

They also note 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.

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To prevent serious diseases of the gut that inflammation causes, Nezis and his colleagues say it is necessary to find ways to control and regulate autophagy.

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

In addition to the link between autophagy and inflammation, the researchers also found that certain foods contain natural compounds which can kickstart autophagy.

“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,” Nezis says.

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The research appears in the journal Nature Communications.

The Biotechnology and Biological Sciences Research Council funded the research.

Source: University of Warwick

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