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Gut immune system may play a role in nutrition

The gut’s immune system not only defends against pathogens but also regulates the intake of nutrients, research in mice finds.


April 13, 2021
By Yale University

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The small intestine is ground zero for survival of animals. It is responsible for absorbing the nutrients crucial to life, and it wards off toxic chemicals and life-threatening bacteria.

In a new study in the journal Science, researchers report the critical role that the gut’s immune system plays in these key processes. The findings may provide insights into origins of metabolic disease and malnutrition that are common in some regions of the world.

“We were surprised that the immune system was so involved in nutrition,” says first author Zuri Sullivan, a former graduate student in the immunology department at Yale University and now a postdoctoral fellow at Harvard University. “And the study lays the groundwork for understanding how this reciprocal interaction works.”

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Working in the lab of senior author Ruslan Medzhitov, professor of immunobiology at Yale and an investigator at the Howard Hughes Medical Institute, Sullivan became interested in how the diets of humans and other animals can dramatically change the organization of their digestive tracts. For instance, the digestive systems of carnivores and herbivores are organized differently to accommodate their specialized diets. Omnivores have the most complex system, which must adapt to a diverse diet of proteins, fats, and carbohydrates depending upon what’s available in the environment.

Sullivan, Medzhitov, and a group of colleagues decided to study how the large numbers of immune cells present inside intestinal tracts might influence nutrition. For instance, a specific immune system signaling molecule, known as interleukin-22 (IL-22), plays a key role in combatting bacterial pathogens such as those that cause food poisoning. The presence of IL-22 also seems to prevent the uptake of certain nutrients in the digestive system when pathogens are present.

In a series of experiments, the researchers discovered that a specific group of immune system cells—gamma delta T cells—can suppress expression of interleukin-22 in mice and allow the cells on the intestinal wall to activate digestive enzymes and nutrient transporters.

In addition to providing insights into malnutrition in some parts of the world—where bacterial infections lead to chronic expression of IL-22 and suppress the uptake of nutrients, the findings might also eventually help researchers develop ways to combat high rates of metabolic diseases, such as type 2 diabetes and obesity in the developed world, Sullivan says.


Original Study DOI: 10.1126/science.aba8310