Microbiome signatures linked to cancer and treatment adverse events in a real-world cohort

The gut microbiome has emerged as a key contributor to cancer biology, yet human studies linking the microbiome to cancer are limited by focus on individual cancers, and inadequate adjustment for cancer-specific clinical features. Here we present findings from a real-world mixed-cancer cohort (Mayo Clinic Cancer Microbiome), comprising 1,364 cancer patients and 287 healthy controls. Using a rigorous framework to account for non-specific microbiome associations with cancer, comorbidities, and clinical variables, we identified 341 cancer-associated species across five cancer classes that represent the most plausible contributors to cancer pathogenesis. Within cancer classes, we found reduced secondary bile acid pathway levels in early-onset breast cancer and elevated Veillonella parvula and stool lactate in early-onset colorectal cancer. Additionally, high levels of Anaerostipes hadrus encoding dihydropyrimidine dehydrogenase were protective against 5-fluorouracil-induced diarrhea. These findings demonstrate the strength of our cohort and provide a foundational resource for discovery of cancer-specific microbiome signatures and predictive biomarkers.