A natural supplement strengthened lasting anticancer immune responses in obese mice.
Weight loss can improve many aspects of health, but the immune system may not recover as quickly. Obesity can leave behind long-lasting changes in the bone marrow, where immune cells are formed, potentially weakening the body’s ability to respond to cancer even after excess weight is lost.
New experiments in mice suggest that a dietary supplement derived from yeast may help undo part of that damage. The supplement contains yeast beta-glucan, a naturally occurring compound already used in commercial food products. When obese mice consumed it, stem cells in their bone marrow were reprogrammed to produce immune cells with stronger anti-tumor activity.
The effect involved innate immunity, the body’s rapid, broad defense system and an important first line of protection against abnormal cells. Researchers from Trinity College Dublin and University College Dublin tested the resulting immune responses against colorectal, skin, and breast cancer cells.
The findings do not establish that yeast beta-glucan can prevent or treat cancer in people, since the study was conducted in mice. They do, however, reveal a potentially important biological pathway and raise the possibility that a widely available dietary compound could one day help restore immune functions disrupted by obesity.
The study appeared in Cell Reports and was led by Frederick Sheedy, Associate Professor in Immunology in Trinity’s School of Biochemistry and Immunology, and Helen Roche, Professor in Nutrigenomics at the UCD School of Public Health, Physiotherapy and Sports Science and Director of the UCD Conway Institute.
A supplement retrains immune development
The central question was whether a supplement taken through food could produce lasting changes in the immune system rather than briefly stimulating cells that were already mature. To investigate that possibility, the researchers focused on the bone marrow, where stem cells generate many of the body’s immune cells.
Dr Anna Ledwith, postdoctoral researcher in Prof. Roche’s group and first author of the research paper, said: “We wanted to investigate whether a common dietary supplement, yeast beta-glucan, could reprogram early-stage immune cells in the bone marrow to produce long-lasting, enhanced anti-tumor immune responses.
“Mice were fed a standard or high-fat diet supplemented with yeast beta-glucan for 4-12 weeks, and then their immune system was challenged by different types of cancer cells: colorectal, skin, and breast cancer. The study also tested whether yeast supplementation could overcome immune dysfunction caused by obesity and whether protective effects persist after weight loss.”
This approach helped distinguish a temporary immune boost from a deeper biological change. After several weeks of supplementation, the researchers exposed the animals’ immune systems to cancer cells and examined whether the newly produced immune cells responded differently.
The experiment also allowed them to ask whether the benefits would remain after weight loss. That question matters because obesity can alter immune memory and cell development in ways that do not necessarily disappear when a person or animal becomes leaner.
Immune benefits persisted after weight loss
The supplement changed stem cells inside the bone marrow, influencing the immune cells they later produced. This created a lasting form of innate immune memory through diet alone, rather than through the injections used in previous experiments.
Commenting on the significance of the findings, Prof. Roche added: “This is the first demonstration that dietary delivery of yeast beta-glucan is sufficient to induce trained immunity through reprogramming of bone marrow stem cells. Previous research required injections.
“Crucially, this dietary intervention restores anti-tumor innate immunity in obese mice and reverses long-term immune memory defects that persist even after weight loss, a major unmet clinical challenge.”
The results suggest that yeast beta-glucan may help reset part of the immune system after obesity has altered it. In the mice, the stronger response continued even after weight loss, indicating that the supplement affected how immune cells were produced rather than only changing body weight or briefly activating existing cells.
Obesity is associated with impaired immune defenses and increased risks of infection and cancer. These effects can persist after weight loss, leaving researchers searching for ways to restore immune function more completely.
The mouse findings raise the possibility that dietary compounds could support that recovery. Human trials would still be necessary to determine whether yeast beta-glucan produces the same immune changes in people, what dose would be appropriate, and whether the approach is safe for patients receiving cancer treatment.
An existing supplement could speed testing
Yeast beta-glucan is already commercially available and has a history of use as a food supplement. That could make it easier to begin carefully controlled human studies than it would be for an entirely new experimental drug.
Researchers are particularly interested in whether dietary supplementation could benefit people living with obesity, chronic infections, or other conditions that weaken immune defenses. Future trials would need to establish who is most likely to benefit and whether the supplement can strengthen immunity without interfering with chemotherapy, immunotherapy, or other treatments.
Looking to the future, Professor Sheedy said: “This research paves the way for dietary intervention studies in people living with obesity, chronic infections and other immunocompromised populations. The yeast beta-glucan used, WellmuneTM, from Kerry Group, is already food-grade and commercially available, facilitating rapid clinical trials.
“Ultimately, a simple dietary supplement could help boost the immune system’s cancer-fighting ability, complementing existing treatments such as chemotherapy and immunotherapy, with the potential to improve vaccine responses and resistance to infection.”
The next step is to determine whether trained immunity can be induced in humans through the same dietary route. Researchers will also need to test how long any benefits last, whether they improve meaningful health outcomes, and whether the supplement can be used safely alongside established cancer therapies.
Reference: “Yeast β-glucan supplementation supports immunometabolic anti-tumor responses and reverses obesity-induced dysfunction via trained hematopoiesis” by Anna E. Ledwith, Hannah Prendeville, Cian JH. Horneck Johnston, Stephen P. Cunningham, John P. McGrath, Carrie Corkish, Aaron M. Walsh, Fatma Koc, Hugo Charles-Messance, Vasile Mihai Sularea, Caitlín Ní Chasaide, Heike C. Hawerkamp, David K. Finlay, Lydia Lynch, Kingston H.G. Mills, Catherine Stanton, Helen M. Roche and Frederick J. Sheedy, 3 July 2026, Cell Reports.
DOI: 10.1016/j.celrep.2026.117648
Support for this work came from Science Foundation Ireland Frontiers for the future awards (19/FFP/6625) to H.M.R. and F.J.S. and Research Ireland Strategic Partnership Precision Oncology Ireland 2 (23/SPP/12064) to H.M.R. It was also supported by Irish Research Council Government of Ireland Postdoctoral Fellowship (GOIPD/2019/807) to H.C.-M., Postgraduate Scholar Award (GOIPG/2021/446) to C.J.H.H.J. and Enterprise Postdoctoral Fellowship (EPSPD/2023/294) to A.M.W.
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