ROCHESTER, Minn. — Mayo Clinic researchers discovered distinct gut microbiome patterns in adults 50 or younger with colorectal and breast cancers compared with those diagnosed later in life — one of several findings from an analysis of stool samples from 1,364 patients with cancer across cancer types, stages and treatments. The study is published in Cell.
Among younger patients, those with colorectal cancer had higher lactate levels and more Veillonella parvula, a gut bacterium that feeds on lactate. Early-onset breast cancer showed changes across 64 bacterial species and lower levels of primary bile acids.
The findings come from the Mayo Clinic Cancer Microbiome cohort, a real-world study that recruited cancer patients at Mayo Clinic in Arizona, Florida and Minnesota, representing 40 states. Stool samples were collected before treatment began and linked to detailed clinical data on side effects and outcomes. The samples provide a window into the gut microbiome, trillions of microbes living in the digestive tract.
Cancer-specific microbiome patterns emerge
Researchers compared patients with cancer with 287 people without it to identify broad microbiome differences. Comparisons across cancers then revealed more specific signals. After accounting for other health conditions, researchers pinpointed 341 bacterial species associated with five cancer groups.
Among those, neuroendocrine tumors showed a broad loss of common health-associated gut bacteria. Liver and intrahepatic bile duct cancers had higher levels of several bacteria, including Enterococcus faecalis. Esophageal cancer had higher levels of six species, including Streptococcus bacteria. Distinct links were also found in lymphoid leukemia and multiple myeloma and related plasma cell cancers.
"We can now narrow the search to those microbial changes that are most specific to individual cancers," says co-corresponding author Ruben Mars, Ph.D. , a microbiome researcher at Mayo Clinic in Minnesota. "Those are the signals we need to understand first if we want to determine whether the microbiome plays a causal role in cancer and ultimately develop targeted interventions."
The findings come as colorectal and breast cancer rates rise among younger adults. Colorectal cancer incidence is increasing about 3% a year among adults ages 20 to 49, while breast cancer incidence is rising 1.4% a year among women younger than 50, according to the American Cancer Society.
The colorectal finding raises questions about a possible biological connection: Tumors can produce high levels of lactate, which V. parvula uses to grow. Whether that relationship plays a role in early-onset disease is not yet known.
In breast cancer, one of the 64 species that differed in younger patients was Clostridium scindens, a bacterium involved in bile acid and steroid metabolism.
No comparable age-related microbiome differences were found in brain cancer , the third cancer examined in the early-onset analysis. The colorectal and breast cancer findings do not establish that these microbial or metabolic differences cause early-onset disease, but they identify links that warrant further study.
Gut microbiome linked to survival and treatment side effects
Researchers identified gut bacteria associated with survival in colorectal, liver and intrahepatic bile duct , ovarian and prostate cancers and melanoma . In liver and intrahepatic bile duct cancer, Bifidobacterium longum was associated with longer survival and Blautia A massiliensis with shorter survival.
Researchers also studied whether the gut microbiome before treatment was associated with diarrhea during chemotherapy , a side effect that can make treatment harder to tolerate. Among patients receiving 5-fluorouracil, or 5-FU, a chemotherapy used to treat many types of cancer, those who later developed diarrhea had lower levels of bacterial genes capable of breaking down the drug. Much of that function came from Anaerostipes hadrus, a common gut bacterium. The same signal was not linked to diarrhea in patients receiving carboplatin, another chemotherapy drug, suggesting the finding was specific to 5-FU.
"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 and Bernard and Edith Waterman Director, Microbiomics Program, 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."
Next, researchers will investigate whether cancer-specific microbial signals play a causal role in disease and validate the microbiome's potential to predict treatment side effects in larger patient groups.
The research was supported in part by the National Institutes of Health and philanthropic gifts from the Valhalla Foundation, the Maxine & Jack Zarrow Family Foundation, and other benefactors to the Mayo Clinic Microbiome Program and Center for Individualized Medicine. For a complete list of authors, disclosures and funding, review the study.
