The gut microbiome might be a crucial factor in how the body responds to cancer.
A recent study has unveiled the significant role that gut bacteria play in influencing whether the amino acid asparagine, found in our diets, will promote tumor growth or rather stimulate immune cells to combat cancer. Researchers from Weill Cornell Medicine have highlighted the importance of the gut microbiome, which consists of trillions of microorganisms residing in our intestines, emphasizing its central role in the body’s cancer response and its interaction with contemporary cancer treatments such as immunotherapy.
Published on January 2 in Cell Host & Microbe, these findings could pave the way for innovative cancer treatment methods and monitoring techniques. Rather than merely targeting tumors directly, physicians might one day reshape the gut microbiome or adjust dietary intake to deprive tumors of necessary nutrients while enhancing the activity of immune cells.
Dr. Chunjun (CJ) Guo, an associate professor of immunology at Weill Cornell and co-lead author of the study, stated, "Our research indicates that we need to consider how the synergy between diet, gut microbiota, and immune cells infiltrating tumors can influence cancer progression and therapeutic responses. This critical level of regulation should not be ignored."
This research stems from a close collaboration with co-corresponding authors Dr. David Artis, who leads the Jill Roberts Institute for Research in Inflammatory Bowel Disease and serves as a Michael Kors Professor in Immunology, and Dr. Nicholas Collins, an assistant professor of immunology affiliated with the Friedman Center for Nutrition, both at Weill Cornell.
The Role of Microbes in Asparagine Depletion
Initially, the researchers conducted experiments using mouse models that were implanted with human gut microbiota to demonstrate that specific bacteria can deplete amino acids, thereby impacting tumor progression. They specifically examined asparagine, an amino acid that plays a vital role in protein synthesis and supports cell survival. Both the cancer cells, which exist in a nutrient-deficient environment within tumors, and CD8+ T cells—immune cells responsible for directly attacking and destroying tumor cells—require asparagine to function effectively.
To delve into the effects of microbiota on asparagine metabolism, the team worked with a common gut bacterium known as Bacteroides ovatus, which possesses a gene called bo-ansB. This gene encodes an enzyme capable of breaking down asparagine. In their mouse model experiments, the researchers found that when the bo-ansB gene was present, B. ovatus consumed more asparagine in the gut, resulting in less of it being absorbed into the bloodstream and consequently reaching the tumors.
Conversely, when the bo-ansB gene was disabled, the bacteria could not deplete asparagine in the intestine, leading to increased levels of the amino acid in the bloodstream and, ultimately, at the tumor site. This finding illustrates that bacteria regulate the amount of asparagine that exits the gut, thus shaping the environment where tumors and immune cells interact.
In mouse models of colorectal cancer that were given additional dietary asparagine, the presence of bacteria with the bo-ansB gene resulted in tumor growth. However, in mice lacking the bo-ansB bacteria, the same asparagine-rich diet yielded a contrasting outcome: greater amounts of asparagine reached the tumor and were taken up by CD8+ T cells, triggering these immune cells to enter a “stem-like” state associated with prolonged and effective anti-tumor responses. In stark contrast, a deficiency in asparagine diminished the ability of CD8+ T cells to inhibit tumor growth.
A Nutrient Switch for Cancer-Fighting Cells
The study illustrated that elevated levels of asparagine within the tumor microenvironment—when the bo-ansB was absent—prompted CD8+ T cells to express higher quantities of a protein transporter (SLC1A5) on their surface, which is crucial for combating cancer cells. Stem-like CD8+ T cells can serve as a renewable source of immune cells that can mature into effective cancer-fighting T cells. Once activated, these T cells attack tumors by producing potent immune factors that assist in destroying cancer cells. Notably, blocking the function of SLC1A5 negated the benefits observed from the increased asparagine levels.
Looking Beyond Asparagine
Beyond the focus on asparagine, the Guo lab is eager to investigate other biological pathways that may influence tumor burden by either suppressing growth or enhancing anti-tumor activity. Dr. Guo noted, "Numerous studies suggest that enzymes produced by our microbiota, as well as metabolites such as small molecules and proteins, could serve as potential biomarkers for cancer progression."
This opens the door to the possibility that future cancer treatments could integrate immunotherapy with customized diets and microbiome-targeted strategies. These might include designing probiotics, engineering native gut bacteria, or creating personalized dietary plans that optimize amino acid availability.
"It’s imperative to continue exploring the interactions between diet, the microbiota, and the immune system, as different diets may enhance the immune response in some individuals but not in others based on their unique microbiota composition. Our aim is to develop personalized therapy, allowing us to tailor specific diets that synergize with each individual’s microbiota to strengthen their immune system against cancer," emphasized Dr. Nicholas Collins, an assistant professor of immunology at Weill Cornell.
Source Information:
Journal Reference: Qiao, S., et al. (2026). "Microbiota utilization of intestinal amino acids modulates cancer progression and anticancer immunity." Cell Host & Microbe. doi: 10.1016/j.chom.2025.12.003.
