Starvation signals control intestinal inflammation in mice

Intestinal inflammation in mice can be dampened by giving them a diet restricted in amino acids, the building blocks of proteins, researchers have found. The results were published online by Nature on Wednesday, March 16.

The findings highlight an ancient connection between nutrient availability and control of inflammation. They also suggest that a low protein diet — or drugs that mimic its effects on immune cells — could be tools for the treatment of inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis.

The research team, led by Emory Vaccine Center immunologist Bali Pulendran, discovered that mice lacking the amino acid sensor GCN2 are more sensitive to the chemical irritant DSS (dextran sodium sulfate), often used to model colitis in animals. This line of research grew out of the discovery by Pulendran and colleagues that GCN2 is pivotal for induction of immunity to the yellow fever vaccine.

“It is well known that the immune system can detect and respond to pathogens, but these results highlight its capacity to sense and adapt to environmental changes, such as nutritional starvation, which cause cellular stress,” he says.

Mice fed a low protein diet (2 percent, compared to 16 percent in a standard diet) or a diet lacking only the amino acid leucine were protected from signs of colitis induced by DSS consumption, such as weight loss and bloody diarrhea. Mice lacking GCN2 were not protected from colitis when fed a low protein diet, which demonstrates that GCN2 is necessary for the protective effect.

More investigation is needed before applying the findings to human disease. The experiments with mice lasted roughly a week, but it is not clear how long a human would need to consume a low-protein diet to have the desired effect, or how low it is necessary to go. A low protein diet is not advisable for long periods, although such a diet is sometimes recommended for people with kidney disease to postpone the need for dialysis.

Posted on by Quinn Eastman in Immunology Leave a comment

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Quinn Eastman

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