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Meds, meals and microbes: gut health on the cancer front line

A fibre-rich, whole foods diet may help boost the immune system to fight cancer.Credit: Mediterranean/Getty Images

"There are more microbial genes in the human body than there are human genes," says Jennifer Wargo, professor of surgical oncology and genomic medicine and core member of the James P. Allison Institute at The University of Texas MD Anderson Cancer Center. "When it comes to our total genomic content, we are nearly 99% microbial, and these organisms and their genes have a tremendous impact on normal physiology and disease.”

Traditional cancer care often relies on using drugs to target aberrant signaling pathways or to bolster the immune response. But at MD Anderson, researchers are pioneering a holistic approach that underlines the gut microbiome's importance in enhancing cancer treatment and prevention — the type of work only made possible by the institution’s unique research environment.

Unlocking the golden gut

Wargo began her exploration of the microbiome over a decade ago when she worked with Ravid Straussman to explore how stromal cells in patient tumours can influence treatment resistance. Their work took a crucial turn when they discovered a patient-derived cell line that repeatedly induced chemotherapy resistance in both pancreatic and colorectal cancer cells.

“We hit a dead-end looking for secreted factors in human tissue,” recalls Wargo. “But after a routine check showed our cell line was contaminated with Mycoplasma, we asked if the bacteria was responsible for the resistance.” The researchers found that eliminating Mycoplasma from stromal cells could reverse drug resistance1 and revealed that cancerous tissues, unlike healthy ones, harboured gammaproteobacteria, uncovering early evidence of distinct tumour microbiomes.

In 2013, Wargo joined MD Anderson to help lead the Melanoma Moon Shot, part of the institution’s collaborative efforts to accelerate the translational of scientific discoveries into clinical advances. Motivated by preclinical research on the gut microbiome’s effect on immunotherapy, her team studied microbiomes from more than 200 patients with metastatic melanoma beginning immunotherapy. They discovered that those with a diverse gut microbiome, especially with increased levels of Ruminococcus, Faecalibacterium, and Bacteroidetes, experienced better treatment results2,3.

Wargo now leads MD Anderson's Platform for Innovative Microbiome and Translational Research (PRIME-TR), harnessing translational microbiome research to transform cancer therapy. The group advances the field through interventional studies, which involve depleting unfavourable microbes or replacing the gut microbiome with ecosystems of rationally designed and organically assembled microorganisms, and fecal microbiota transplants (FMT) to improve response and reduce toxicity.

“We’re tackling several big questions around the microbiome in the gut and other sites to promote health and end cancer,” Wargo says. “We’re working with investigators at MD Anderson and around the world to derive novel microbiome-based strategies to improve immunity and responses to cancer treatment.”

Gut signals, tumour secrets

As a physician-scientist initially trained in immunology and host defense, MD Anderson’s Florencia McAllister, associate professor of clinical cancer prevention and gastrointestinal medical oncology, has made significant contributions to the understanding of the tumour microbiome and the interplay between host and microbes, from onset to treatment resistance.

"There's growing evidence of microbes in various tumours, not just the gut,” she explains. “As we’ve learned about the microbiome and its association with disease and treatment responses, we’re now developing a mechanistic understanding of these relationships and moving our findings toward clinical translation.”

McAllister and her team demonstrated that pancreatic cancer patients with more diverse tumour microbiomes experience improved post-surgery outcomes. They further validated this by transferring fecal microbes from these patients to mice, affecting tumour growth and highlighting gut-pancreatic tumour communication. This discovery has informed a phase zero clinical trial exploring fecal transplants in patients with pancreatic cancer undergoing surgery, which McAllister now leads.

In a recent study4, McAllister and colleagues revealed that altering a specific immune signal in the gut known as IL-17 can disrupt its microbial balance. This disruption can encourage the growth of tumours even in distant parts of the body, due to changes in the immune response. The study, notable for its use of genetic models, immunoprofiling and single-cell transcriptomic analysis, offers fresh perspectives on microbially targeted cancer therapies.

“Our findings highlight a complex relationship between IL-17 pathways and cancer treatment,” says McAllister. “Inhibiting IL-17 can disrupt gut microbiota and impact tumour control efforts. Strategies such as FMT may be required to preserve microbial balance, informing trial designs and oncologists, particularly when patients don't respond to treatments as anticipated.”

The fibre fix

As the significance of the gut microbiome in cancer treatment gains recognition, diet has emerged as a new frontier in combating the disease. Carrie Daniel-MacDougall, associate professor of epidemiology and faculty director of MD Anderson’s Bionutrition Research Core, is at the forefront of translating this understanding into actionable strategies. Emphasizing a fibre-rich, whole foods diet, she explains how altering the microbiome can amplify the body's immune response against tumours.

“I'm focused on using nutrition to help cancer patients, both to make treatment more tolerable and to improve their outcomes,” she says. “Prebiotic foods, such as nuts, beans and whole grains, offer a mix of soluble and insoluble fibre, proteins, and healthy fats that work together to stimulate the microbiome.”

Building on the foundational work at MD Anderson, Daniel-MacDougall and colleagues are testing specific dietary interventions to manipulate the microbiome and influence treatment outcomes. The team recently found that adding legumes, such as navy beans, to the diet increased microbiome diversity and enriched bacteria that maintain gut health5. They also saw parallel shifts in circulating anti-inflammatory metabolites and immune proteins in the patients.

“We’ve seen rapid changes in the microbiome with these dietary interventions,” Daniel-MacDougall notes. “The issue is that without ongoing support, patients often revert to their old eating habits, and then the microbiome flips back as well. Diet is a constant factor in the health of our patients and without support or monitoring, we are ignoring an important variable and potential ally in health outcomes.”

From insight to impact

The work of these and many other researchers showcases MD Anderson’s ability to propel translational research through collaborative science. “It’s about learning from our patients, bringing those insights back to preclinical models, and applying that knowledge back in real time,” says Wargo. “MD Anderson has really championed this approach to team science — it’s about breaking down silos, getting everyone to work together, and providing them with the tools and resources they need to drive impactful discoveries.”

For McAllister, the extensive collaboration, a vast patient base, and a culture committed to deep understanding and rapid translation sets the stage for unparalleled research opportunities at MD Anderson. Joining the basic science discoveries from her lab with clinical insights, she plans to continue translating breakthroughs into impactful advances for patients.

“We’re just starting to distinguish between ‘passenger’ and stable microbes in tumours,” McAllister says. “Their dynamics, affected by diet and stress, can alter therapy responses. This knowledge could enhance precision medicine, as certain microbes might influence chemotherapy or immunotherapy effectiveness.”

To discover more about MD Anderson’s groundbreaking research into cancer and the microbiome, click here.


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