Younger adults with colorectal, breast cancer show distinct gut bacteria

Clinical takeaway: Younger patients with colorectal or breast cancer carry measurably different gut bacteria than older patients, an association that gives the search for early-onset drivers a concrete place to start. 

Colorectal and breast cancers are turning up in patients their physicians once considered too young for them. Colorectal cancer incidence is rising about 3% per year among US adults ages 20 to 49 and breast cancer is climbing among women younger than 50, with no explanation yet for either trend. 

Whether the bacteria living in the gut have any part in that shift, or in how patients fare once treatment starts, has been hard to establish. Gut microbes number in the trillions, and studies tying them to cancer have struggled to say which changes belong to which disease. A new analysis from Mayo Clinic takes the question on directly by profiling patients' gut microbiomes across cancer types before treatment began and mapping where the differences lie. 

Patients diagnosed with colorectal cancer at age 50 or younger carried higher lactate levels and more Veillonella parvula, a gut bacterium that feeds on lactate, than patients diagnosed later. Early-onset breast cancer showed shifts across 64 bacterial species and lower levels of primary bile acids. Brain cancer, the third cancer examined for age-related differences, showed none. Researchers noted that colorectal tumors can generate substantial amounts of lactate, potentially creating conditions that favor V parvula growth, although the significance of this association is unknown.

Many microbiome changes shared across cancers traced to comorbidities rather than the cancers themselves; after accounting for them, the analysis linked 341 bacterial species to five cancer groups. Neuroendocrine tumors showed a broad loss of health-associated gut bacteria, liver and intrahepatic bile duct cancers carried higher levels of several species including Enterococcus faecalis, and esophageal cancer ran higher in six species including Streptococcus species. Specific bacteria also tracked with survival in colorectal, ovarian, and prostate cancers, melanoma, and liver and intrahepatic bile duct cancer, where Bifidobacterium longum accompanied longer survival and Blautia A massiliensis shorter. 

The pretreatment microbiome also pointed toward who would struggle with chemotherapy. Patients who later developed diarrhea on 5-fluorouracil (5-FU) carried lower levels of bacterial genes capable of breaking down the drug, much of that capacity residing in the common gut bacterium Anaerostipes hadrus. The same pattern did not appear in patients receiving carboplatin, which suggests the finding is specific to 5-FU. 

The Mayo Clinic Cancer Microbiome cohort recruited 1,364 patients with cancer at Mayo sites in Arizona, Florida, and Minnesota, drawing from 40 states, along with 287 people without cancer for comparison. Stool samples were collected before treatment began and linked to clinical data on side effects and outcomes. 

The Mayo team plans to probe whether the cancer-specific microbial signals play any causal role in disease and to check the toxicity prediction in larger patient groups, the step that would determine whether a pretreatment stool sample can tell an oncologist which patients need closer monitoring on 5-FU. For now, the study's main value is in guiding future research: rather than searching across trillions of microbes, investigators can focus on a defined set of microbial candidates linked to specific cancer types.

"The microbiome is not the sole driver of cancer or treatment outcomes, but it is an underappreciated component that has not traditionally been considered in therapeutic approaches," says co-corresponding author Purna Kashyap, M.B.B.S., director of the Mayo Clinic Microbiome Program at the Mayo Clinic Center for Individualized Medicine. "This gives us a proof of concept that we can begin to understand why some patients experience a particular side effect and identify a target that could potentially be acted upon." 

Source: Yang L, et al. (2026 Sep 29) Cell. Microbiome signatures linked to cancer and treatment adverse events in a real-world cohort