Scientists cast new light on how fasting impacts the immune system

New research from The University of Manchester may reshape our understanding of what happens to the immune system when we fast.

Funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the study on mice shows that the brain’s hypothalamus controls how the immune system adapts during fasting, through a handful of highly specialized neurons responsible for making animals hungry.

Published today (04/04/25) in Science Immunology—one of the world’s leading immunology journals—the study shows the brain’s perception of hunger or fullness, rather than actual eating or caloric restriction, is enough to drive changes in the body’s immune cells.

The findings cast doubt on the current view that a lack of nutrients alone controls how the immune system responds to fasting, indicating the brain has a critical role, beyond the simple absence of food.

By artificially switching on specific brain neurons in mice—which typically signal low energy levels—scientists induced a synthetic sense of hunger. Remarkably, within hours, they saw a fast reorganization of immune cells in the blood, with a noticeable drop in inflammatory monocytes. These artificially hungry mice looked, from an immune perspective, just like mice that had fasted for real.

This discovery could have important implications for developing new therapies to treat a range of inflammatory diseases as well as for treating wasting syndromes seen in cancer, in which individuals lose weight despite eating normally.

It may also explain why obesity often accompanies inflammatory conditions and why malnourished individuals are more prone to infections and inflammation.

The lead senior researcher, Dr Giuseppe D’Agostino, who coordinated the study, said: “Our perceptions can shape our bodies in ways we don’t always notice. It’s easy to see how thoughts guide our actions, but this study reminds us that even our internal body adjustments that are not under conscious control respond to the brain’s signals.

“This study underlines how important the brain is in regulating the immune system. But if internal or external factors alter the brain’s perception, these processes can go awry, reminding us how deeply the mind and body are—and should remain—connected.

"In addition to BBSRC who funded the work, we are grateful to the Medical Research Council for providing early-stage seed funding that helped the lab explore completely novel areas — a small but truly visionary contribution that still resonates today."

This work challenges the long-standing view that fasting’s immunological impact is driven purely by nutrient levels. It highlights the nervous system’s profound influence on how the immune system adapts during fasting.”

Professor Matt Hepworth, Collaborator and Manchester immunologist, The University of Manchester

Lead author Dr Cavalcanti de Albuquerque said: “By showing how the brain exerts top-down control over immune cells, we can further explore when and how fasting might deliver health benefits. It also opens up potential ways to treat infectious, inflammatory, metabolic, and psychiatric conditions.”