New research shows the trillions of microbes in the human gut play a central role in how the body responds to cancer and its treatments. Scientists are finding that the gut microbiome can improve the effectiveness of immunotherapies and chemotherapy, while also reducing harsh side effects for patients. This understanding is opening new avenues for personalized cancer care.[mdpi+2]
Microbiome's Impact on Immunotherapy and Chemotherapy
The gut microbiome, a complex ecosystem of bacteria, fungi, and other microbes, directly influences the immune system. This interaction is crucial for how well cancer treatments work. For example, certain gut bacteria can make immune checkpoint inhibitors (a type of immunotherapy) more effective at fighting tumors. These drugs "release the brakes" on immune cells, allowing them to attack cancer. However, only a fraction of patients respond to these powerful therapies.[mdpi+4]
"Recent research has implicated the microbiome in the metabolism, absorption and even mechanism-of-action of both chemotherapy and immunotherapy," said Dr. Peter Turnbaugh, a professor of microbiology and immunology at UC San Francisco. "While much of the data comes from cell culture or animal models, compelling associations are now emerging in human patients as well."[technologynetworks]
Chemotherapy also interacts with gut microbes. Some bacteria can break down chemotherapy drugs, making them less toxic or even enhancing their anti-cancer effects. For instance, researchers at UC San Francisco found that some gut bacteria can "gobble up" chemotherapy drugs like fluoropyrimidines and turn them into harmless byproducts. This process can significantly reduce severe side effects such as nausea and vomiting.[oncologynews]
Fecal Transplants Show Promise
Fecal microbiota transplantation (FMT), often called "poop pills," is emerging as a promising strategy to improve cancer treatment outcomes. FMT involves transferring stool from healthy donors to cancer patients to restore a balanced gut microbiome.[cancer+2]
Recent Canadian clinical trials, published in the journal Nature Medicine, showed dramatic improvements. One study found that FMT eliminated toxic side effects of drugs used to treat kidney cancer. Another study revealed that 80% of lung cancer patients responded to immunotherapy after FMT, compared to only 39-45% who typically benefit from immunotherapy alone. Similarly, 75% of melanoma patients who received FMT responded positively to treatment, compared to 50-58% with immunotherapy alone.[lhscri]
Dr. Arielle Elkrief, a co-principal investigator from Université de Montréal, noted that their clinical trial showed FMT could improve immunotherapy efficacy in lung cancer and melanoma patients. She also said the results suggested a mechanism where FMT eliminates harmful bacteria after the transplant.
In an earlier study from February 2021, researchers at the National Cancer Institute (NCI) and UPMC Hillman Cancer Center found that some advanced melanoma patients who initially did not respond to immunotherapy started responding after receiving FMT from patients who had responded well to the treatment.[lhscri]
Dr. Giorgio Trinchieri, chief of the Laboratory of Integrative Cancer Immunology in NCI's Center for Cancer Research, stated, "Our study is one of the first to demonstrate in patients that altering the composition of the gut microbiome can improve the response to immunotherapy." He added that the data proves the gut microbiome can be a therapeutic target in cancer.[cancer]
How Gut Microbes Influence Immune Response and Drug Metabolism
The gut microbiome modulates immune activity by affecting immune cells like T cells, which are vital for targeting tumors. Specific microbial species can boost the effectiveness of immune checkpoint inhibitors. For example, some studies found that Bacteroides fragilis or Bifidobacterium species could enhance the efficacy of these therapies in mouse models.
Microbial metabolites also play a key role. A natural compound from gut bacteria, Bac429, slashed lung tumor growth by 50% when combined with immunotherapy in mice, according to UF Health Cancer Institute scientists. This compound is now "drug-ready" for human trials. Dr. Christian Jobin, one of the researchers, said Bac429 works like the six "superstar" bacteria they identified, but as a simple drug, avoiding fecal transplants.[mdpi+1]
Chemotherapy drugs can also be affected by microbial enzymes. Certain bacterial enzymes, like β-glucuronidases, can reactivate inactive chemotherapy metabolites, potentially increasing their therapeutic effect. However, these same enzymes can also lead to severe gastrointestinal toxicities, such as diarrhea, by reactivating drugs like irinotecan. Inhibiting these microbial enzymes in preclinical studies reduced toxicity.[youtube]
Conversely, some bacteria can inactivate chemotherapy agents. For instance, Gammaproteobacteria-derived cytidine deaminase can inactivate gemcitabine, reducing its efficacy. Preclinical models showed that inhibiting this bacterial enzyme with ciprofloxacin restored gemcitabine's anti-cancer activity.[mdpi]
Beyond Treatment Efficacy: Reducing Side Effects and Preventing Metastasis
The gut microbiome also significantly contributes to chemotherapy-induced toxicity. Researchers at UC San Francisco found that measuring the abundance of helpful bacteria could predict if a patient would develop severe side effects from chemotherapy. When these drug-processing microbes were given to mice experiencing severe side effects, their symptoms greatly improved. This suggests these bacteria could be used as probiotics for humans.
Chemotherapy can also reshape gut bacteria in ways that influence metastasis, the spread of cancer. A study published January 22, 2026, found that chemotherapy alters gut microbiota, sending signals that reprogram immune cells. This can make organs like the liver more resistant to metastatic cancer. Ludivine Bersier, the study's first author, said they were surprised how a chemotherapy side effect could trigger such a structured systemic response, making the body less hospitable to metastasis.[oncologynews]
Probiotics and prebiotics, which are beneficial bacteria and the food that feeds them, may help maintain gut health, reduce inflammation, and mitigate side effects like diarrhea and fatigue during cancer treatment. They can also activate immune cells that target abnormal cancer cells and enhance the effectiveness of immunotherapies. However, patients should consult their care team before taking probiotic or prebiotic supplements, as they can sometimes interact with cancer treatments.[scitechdaily+2]
Future of Personalized Cancer Care
The growing understanding of the gut microbiome's role is paving the way for personalized cancer treatments. Scientists are looking into modifying patients' microbiomes to improve treatment responses and reduce toxicity. This includes approaches like tailored diets, engineered probiotics, and even personalized dietary plans that fine-tune amino acid availability.
Dr. Chunjun (CJ) Guo, an associate professor of immunology at Weill Cornell Medicine, said their study suggests that the interplay of diet, gut microbiota, and tumor-infiltrating immune cells affects cancer growth and treatment response.[news]
"Our goal is personalized therapy, where we can tailor a specific diet that will synergize with the microbiota of an individual to boost the immune system against cancer," said Dr. Nicholas Collins, assistant professor of immunology at Weill Cornell.[news+1]
While significant progress has been made, experts caution that there is currently no direct evidence that the human commensal microbiome is a key determinant in the initial development of cancer. However, they agree it is a crucial factor interacting with environmental factors and a patient's genetic vulnerability to cause cancer. The field is rapidly expanding, with new discoveries about bacterial species, metabolites, and their impact on various cancers emerging yearly.[news+1]
