The brain alone can trigger immune changes associated with fasting, reshaping how we understand the mind-body connection in immune health.
New research from the University of Manchester is challenging long-held beliefs about how the immune system behaves during periods of fasting.
Supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC), the study was conducted in mice and identifies a central role for the hypothalamus in regulating immune system responses. Specifically, a small group of specialized neurons in the hypothalamus, those responsible for triggering the sensation of hunger, were found to control how the immune system adapts when food is withheld.
The study, published in Science Immunology, reveals that the brain’s perception of hunger or satiety alone can alter immune cell behavior. This means that changes in the immune system are not solely driven by actual food intake or caloric restriction.
These findings challenge the traditional view that nutrient deprivation is the primary factor influencing immune function during fasting. Instead, the results highlight the brain’s active role in shaping immune responses, suggesting that neural signals may be just as important as nutritional signals in this process.
Mimicking Fasting Through Neural Stimulation
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 Brain-Body Connection
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.”
Collaborator and Manchester immunologist Professor Matt Hepworth added: “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.”
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.”
Reference: “Brain sensing of metabolic state regulates circulating monocytes” by Joao Paulo Cavalcanti de Albuquerque, Jenna Hunter, Rita G. Domingues, Erika Harno, Amy A. Worth, Fabrizio Maria Liguori, Aurora D’Alessio, Gabriella Aviello, David Bechtold, Anne White, Simon M. Luckman, Matthew R. Hepworth and Giuseppe D’Agostino, 4 April 2025, Science Immunology.
DOI: 10.1126/sciimmunol.adr3226
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