Gut bacteria may hold clues to cancer survival and chemotherapy side effects before treatment even begins.
A tumor can produce large amounts of lactate, a molecule that certain intestinal bacteria consume as food. Mayo Clinic researchers found higher levels of lactate and one of these bacteria, Veillonella parvulain adults diagnosed with colorectal cancer at age 50 or younger than in patients diagnosed later in life.
The incidence of colorectal cancer is increasing about 3% per year among adults ages 20 to 49, according to the American Cancer Society. The incidence of breast cancer is also increasing, increasing by 1.4% per year among women under 50. Mayo’s findings identify specific microbial differences to study as researchers work to understand cancers diagnosed at younger ages.
Mayo Clinic researchers analyzed stool samples from 1,364 cancer patients, examining the billions of microbes living in their digestive tracts. Patients represented 40 states and provided samples before beginning treatment at the Mayo Clinic in Arizona, Florida and Minnesota. The team linked these samples to clinical records covering cancer types, stages, treatments, side effects and outcomes, allowing researchers to examine both patients’ diagnoses and what happened during their care. The study, part of the Mayo Clinic Cancer Microbiome cohort, appears in Cell.
Intestinal characteristics of breast cancer differ by age
Younger breast cancer patients also had a different microbial profile than those diagnosed later in life, with changes in 64 bacterial species. One was Clostridium scindenswhich helps process bile acids and steroid molecules. These patients also had lower levels of primary bile acids, substances made by the liver that help digest fats.
Patients with brain cancer, the third cancer examined in the age analysis, showed no comparable differences between younger and older adults. The age-related patterns in colorectal and breast cancers therefore do not extend to all cancers examined by the team, and the study did not establish that these patterns cause early-onset disease.
341 species linked to five cancer groups
Comparing cancer patients with 287 people without cancer helped researchers identify broader differences in gut microbes. They then compared patients of different cancer types to distinguish changes associated with particular cancers. After accounting for other health issues, the team identified 341 bacterial species associated with five cancer groups.
Patients with neuroendocrine tumors had significant loss of common gut bacteria associated with health, while those with liver and intrahepatic bile duct cancers had higher levels of several bacteria, including Enterococcus faecalis. Esophageal cancer was associated with higher levels of six species, including Streptococcus bacteria. Researchers also found distinct associations in lymphocytic leukemia, multiple myeloma, and related plasma cell cancers.
“We can now narrow the search down to the microbial changes most specific to individual cancers,” says co-corresponding author Ruben Mars, Ph.D., a microbiome researcher at the Mayo Clinic in Minnesota. “These are the signals we need to first understand if we are to determine whether the microbiome plays a causal role in cancer and ultimately develop targeted interventions.” »
Matching microbial profiles with patients’ clinical findings extended the analysis beyond differences at diagnosis. Researchers have identified gut bacteria associated with survival in colorectal, hepatic, and intrahepatic bile duct, ovarian, and prostate cancers, as well as melanoma. In liver and intrahepatic bile duct cancers, Bifidobacterium longum was associated with longer survival, while Blautia A massiliensis was associated with shorter survival.
Bacterial genes linked to diarrhea due to chemotherapy
Samples collected before treatment also allowed researchers to look for links between gut bacteria and how patients tolerated chemotherapy. Among patients receiving 5-fluorouracil, or 5-FU, those who later developed diarrhea had lower levels of bacterial genes capable of breaking down the drug. Much of this drug processing capacity came from Anaerostipes hadrusa common intestinal bacteria.
Patients receiving carboplatin, another chemotherapy drug, did not show the same link between these genes and diarrhea. This contrast suggests that the finding was specific to 5-FU, which is used to treat many types of cancer, rather than a general association with diarrhea during chemotherapy.
“This gives us a proof of concept that allows us to begin to understand why some patients experience a particular side effect and identify a target that can be acted upon,” says co-corresponding author Purna Kashyap, MBBS, director of the Mayo Clinic Microbiome Program. “The microbiome is not the sole driver of cancer or treatment outcomes, but it is an underappreciated element that has not traditionally been considered in therapeutic approaches. »
The team will now test whether microbial signals can predict treatment side effects in larger groups of patients. They will also study whether specific cancer microbes contribute to the disease, including V. parvula the ability to feed on lactate in the gut plays a role in colorectal cancer in young adults.
Reference: “Microbiome Signatures Linked to Cancer and Adverse Treatment Events in a Real-World Cohort” by Lu Yang, Vaidhvi Singh, Brent J. Gawey, Jason P. Sinnwell, Stephen Johnson, Elle C. Billings, Trena M. Van Gorp, Jonathan J. Harrington, Michael Q. Slama, Lisa M. Till, Manavjot Singh, Thoshik R. Samineni, Mojun Zhu, Krishna R. Kalari, Gianrico Farrugia, Jun Chen, Ruben AT Mars and Purna C. Kashyap, September 29, 2026, Cell.
DOI: 10.1016/j.cell.2026.09.009
The research was supported in part by the National Institutes of Health and by philanthropic gifts from the Valhalla Foundation, the Maxine & Jack Zarrow Family Foundation, and other benefactors from the Mayo Clinic Microbiome Program and the Center for Individualized Medicine.
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