23 Mayo Clinic researchers have identified distinct gut microbiome patterns in adults aged 50 or younger with colorectal and breast cancers compared with those diagnosed later in life. The study, published in Cell, is part of a broader analysis of stool samples from 1,364 patients with cancer across different types, stages, and treatments. The samples come from the Mayo Clinic Cancer Microbiome cohort, a real-world study that recruited patients with cancer at Mayo Clinic sites in Arizona, Florida, and Minnesota, covering 40 states. Stool samples were collected before treatment started and linked to detailed clinical data on side effects and outcomes. The samples offer insight into the gut microbiome, the trillions of microbes that live in the digestive tract. Researchers compared patients with cancer with 287 people without cancer to identify broad microbiome differences. Further comparisons across cancer types revealed more specific signals. After accounting for other health conditions, the team pinpointed 341 bacterial species linked to five cancer groups. Among younger patients, those with colorectal cancer showed higher lactate levels and a greater abundance of Veillonella parvula, a gut bacterium that feeds on lactate. Tumours can produce high levels of lactate, which V. parvula uses to grow, raising questions about a possible biological link. Whether this relationship contributes to early-onset disease remains unknown. Early-onset breast cancer was associated with changes across 64 bacterial species and lower levels of primary bile acids. One of these species was Clostridium scindens, which is involved in bile acid and steroid metabolism. No comparable age-related microbiome differences appeared in brain cancer, the third cancer examined in the early-onset analysis. The colorectal and breast cancer findings do not prove that these microbial or metabolic differences cause early-onset disease, but they identify associations that warrant further investigation. The findings arrive as rates of colorectal and breast cancer continue to rise among younger adults. According to the American Cancer Society, colorectal cancer incidence is increasing by about 3% a year among adults aged 20–49, while breast cancer incidence is rising by 1.4% a year among women younger than 50. Neuroendocrine tumours 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. Oesophageal cancer displayed higher levels of six species, including Streptococcus bacteria. Distinct associations also appeared in lymphoid leukaemia, 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, PhD, 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.” Researchers also identified gut bacteria linked to survival in colorectal, liver and intrahepatic bile duct, ovarian, and prostate cancers, as well as melanoma. In liver and intrahepatic bile duct cancer, Bifidobacterium longum was associated with longer survival, while Blautia massiliensis was associated with shorter survival. The team examined whether the gut microbiome before treatment was linked to diarrhoea during chemotherapy, a side effect that can reduce treatment tolerance. Among patients receiving 5-fluorouracil (5-FU), a chemotherapy drug used for many cancers, those who later developed diarrhoea 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 diarrhoea in patients receiving carboplatin, 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, MBBS, director of the Mayo Clinic 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 plan to investigate whether cancer-specific microbial signals play a causal role in disease and to 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.