Safety testing

Intestinal bacteria can be the deciding factor between promoting tumors and strengthening the immune system

According to researchers at Weill Cornell Medicine, new research reveals how the bacteria in the gut can help determine whether the amino acid asparagine in food will stimulate tumor growth or stimulate cells to fight cancer.He casts the gut microbiome, which consists of trillions of microorganisms that live in the gut, as a player in the body's response to cancer and modern cancer treatments such as immunotherapy.

The results of the study, published in Cell Microbe and Host, could lead to new cancer treatment and monitoring strategies: Instead of targeting tumors directly, doctors can reshape the gut microbiota or reduce food intake to tumors while the immune system is in overdrive.

"Our research tells us that we need to consider how the relationship between food, gut microbiota and tumor-infiltration affects the development of cancer and the response to treatment. We cannot lose sight of this basic principle," said Dr. Chunjun (CJ) Guo, Halvorsen Family Research Scientist, Metabolic Health and Assistant Professor of Immunology at Weill Cornell.

The research is the result of close collaboration with co-authors Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease and the Michael Kors Professor of Immunology, and Dr. Nicholas Collins, assistant professor of immunology and member of the Friedman Center for Nutrition, both at Weill Cornell.

Microbes destroy asparagine in the gut

Scientists found for the first time in mouse models with human gut microbiota that certain bacteria can deplete amino acids and influence cancer progression.They then focused on asparagine, an amino acid that supports protein synthesis and promotes cell survival.Both cancer cells in the nutrient-poor environment within the tumor and CD8+ T cells, cytotoxic immune cells that directly attack and destroy cancer cells, require amino acid activity.

To understand the impact of microbial asparagine metabolism, the team worked with Bacteroides ovatus, a common gut bacterium with a gene called bo-ansB, which encodes an enzyme that breaks down asparagine.Using a mouse model, the researchers showed that when the bo‑ansB gene is present, B. ovatus consumes more asparagine in the gut, so that less is absorbed into the bloodstream and sent to tumors.

When the bo-ansB gene was deleted, the bacteria were unable to remove asparagine, so more of the amino acid reached the bloodstream and intestines.This showed that bacteria control the overall level of asparagine that exits the gut and shapes the battleground between cancer and immune cells.

In mouse models of colorectal cancer fed extra asparagine, bacteria with bo-ansB helped tumors grow.In mice with the bacteria knocked out with bo-ansB, the same asparagine-rich diet had the opposite effect: more asparagine reached the tumor and was taken up by CD8+ T cells.This resulted in immune cells having a "stem-like" state associated with effective and long-lasting antitumor responses.Conversely, without sufficient asparagine, CD8+ T cells were less effective at suppressing tumor growth.

A nutrient switch for cancer-killing cells

Studies have shown that when bo-ansB is removed, asparagine levels are higher in the tumor microenvironment, causing CD8+ T cells to express more of a protein transporter (SLC1A5) on their cell surface, which is important in fighting cancer cells.Stem-like CD8⁺ T cells are a renewable source of immune cells that can mature into cancer-fighting T cells.Once activated, these killer cells help destroy cancer cells by producing powerful immune factors that attack tumors.Blocking SLC1A5 eliminated the benefits of high levels of asparagine.

Besides asparagine, Guo's laboratory is interested in exploring other methods that can influence tumor weight by inhibiting growth or enhancing antitumor activity.

Dr. Guo, who is also a member of the Jill Roberts Institute for Inflammatory Bowel Disease, said: "Many studies show that enzymes produced by our microbiota, as well as metabolites such as small molecules and proteins, can be potential biomarkers for cancer development."

This raises the possibility that future cancer care may combine immunotherapy with tailored diet and strategies targeting the microbiome, such as designing probiotics, native gut bacteria, or personalized nutritional plans that adjust amino acid availability.

"We think it's important to continue to study the interaction between diet, microbiota and the immune system, because different diets can improve one individual's immune system but not another, depending on what type of microbiota they have," said Dr.Collins.

Shanshan Qiao et al.Gut amino acid microbiota utilization modulates tumor progression and antitumor immunity Cell Host & Microbe (2026) doi: 10.1016/j.chom.2025.12.003

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