The trillions of microbes that live in the human gut may influence how cancer develops — and how patients respond to treatment.

Researchers at Mayo Clinic are studying that connection by analyzing stool samples from patients with cancer, looking for microbial signatures associated with treatment response, side effects and disease outcomes. Their goal is to determine whether the microbiome could one day provide another source of information for tailoring cancer treatment to individual patients.

The research is centered on the Oncobiome Project, an initiative within Mayo Clinic’s Center for Individualized Medicine. The project has assembled more than 2,000 stool samples from patients with a range of cancers across Mayo Clinic campuses in Minnesota, Arizona and Florida.

The samples were collected before treatment began, allowing researchers to examine whether a patient’s gut microbiome is associated with how well treatment works, the side effects that develop and longer-term outcomes. They are also studying the enzymes and metabolites produced by gut microbes and whether those molecules offer additional clues about a patient’s response to cancer therapies.

The long-term goal is to determine whether information from the microbiome can be combined with genetics and other biological data to provide a more complete picture of each patient and help physicians make more precise treatment decisions.

“Ultimately, we hope to individualize treatment plans that provide the right drug at the right time based on a person’s unique microbiome and genetics,” says Purna Kashyap, M.B.B.S., the Bernard and Edith Waterman Director of the Mayo Clinic Microbiomics Program.   

Decoding microbiome's cancer link through stool analysis

With samples from patients with different cancers, stages of disease and treatment regimens, researchers can look for microbial patterns that appear across groups. One area of investigation is whether those patterns are associated with event-free survival in patients with cancers such as lymphoma.

The researchers are also looking beyond which microbes are present. They are studying the enzymes, metabolites and other molecules produced by gut microbes to better understand how the microbiome may interact with cancer treatments and the immune system.

"We included a diverse group of patients at various stages of different cancers and undergoing various treatments. This allows us to identify microbial patterns that forecast optimal cancer outcomes, independent of the underlying cancer," Dr. Kashyap says. 

The team is combining microbiome findings with other layers of biological information, including genomics, proteomics, metabolomics, transcriptomics and exposomics. Researchers hope this broader view will help them understand how a patient's microbes, genes, immune system and environmental exposures may contribute to differences in cancer and treatment outcomes.

Ruben Mars, Ph.D., a research scientist at the Center for Individualized Medicine, is playing a key role in spearheading several studies within the Oncobiome project to understand the impact of microbes on cancer risk, treatment efficacy and the underlying mechanisms of any treatment side effects. 

"Although a diverse and balanced gut microbiome is widely recognized as beneficial for our health, pinpointing specific microbial changes that enhance treatment outcomes remains challenging," Dr. Mars says. "Through the Oncobiome project, we're optimistic about developing innovative methods to manipulate the microbiome and ultimately improve cancer care for patients." 

Connecting the microbiome to health outcomes

This research is part of a broader series of the team's investigations into the microbiome. Their recent published studies focus on the microbiome's role in gut-brain disorders, including how bacteria affect intestinal functions like motility. Other published work examines C. difficile infections, exploring how the bacteria persist in the intestine.

Mayo's microbiome scientists are also studying the impact of the gut microbiome on the progression of rheumatoid arthritis and patients' response to treatment. In another study, the team linked a specific microbe, Porphyromonas somerae, to endometrial cancer, finding its intracellular activity may play a pathogenic role in the disease. 

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